Depression Research: 2002-2006
     
Curr Psychiatry Rep. 2006 Oct;8(5):363-70.
Treating Depression in Substance Abusers.
Nunes EV, Levin FR.
New York State Psychiatric Institute, 1051 Riverside Drive (Unit 51), New York, NY 10032, USA. nunesed@pi.cpmc.columbia.edu.

The literature on the diagnosis and treatment of depression is reviewed to arrive at recommendations for clinical practice, future research, and models of service delivery. The DSM-IV criteria are found to provide a sound basis for diagnosis, and a review of placebo-controlled trials of antidepressant medications among substance-dependent patients suggests medication is effective in the setting of careful diagnosis, preferably during a currently observed abstinent period. Clinical recommendations offered for the approach to patients with co-occurring depression and substance dependence include the following: 1) Initiate treatment for substance dependence and encourage abstinence; 2) Conduct a careful psychiatric history and applyDSM-IV criteria for primary or substance-induced depression; 3) If depression meets diagnostic criteria and persists despite treatment of substance use disorder, treat the depression. Future research should include trials of psychotherapeutic or behavioral treatments, studies of treatment algorithms and of integrated systems of care, and studies of methods for disseminating diagnostic and treatment methods in an effort to diminish traditional boundaries between the skill sets of mental health and substance abuse clinicians.

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Psychopharmacology (Berl). 2006 Oct;188(3):273-80. Epub 2006 Sep 8.
Dose-response relationship of duloxetine in placebo-controlled clinical trials in patients with major depressive disorder.
Bech P, Kajdasz DK, Porsdal V.
Psychiatric Research Unit, Frederiksborg General Hospital, Dyrehavevej 48, DK-3400, Hilleroed, Denmark, pebe@fa.dk.

RATIONALE: The optimal dose for achieving the maximum antidepressive effect of selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenalin reuptake inhibitors (SNRIs) remains a controversial issue. The varying sensitivity of scales that measure the severity of depression is one of the many factors affecting the evaluation of the dose-response relationship with antidepressants. OBJECTIVES: To determine if the 6-item Hamilton rating scale for depression (HAM-D(6)) demonstrates a clearer association between dose and antidepressive effect compared with the 17-item Hamilton rating scale for depression (HAM-D(17)) for fixed doses of duloxetine hydrochloride (40, 60, 80, and 120 mg daily) from six double-blind, randomized, placebo-controlled clinical trials assessing safety and efficacy in the acute treatment of patients with DSM-IV-defined major depressive disorder (MDD). METHODS: Mantel-Haenszel adjusted effect sizes were determined by dose for change from baseline to endpoint in HAM-D(6) and HAM-D(17) scores from the six studies. To confirm, assessments were repeated on the subset of the population corresponding to the 70% of patients with the longest duration of treatment regardless of study, treatment, dose, geography, or completion status. RESULTS: For the majority of assessments, HAM-D(6) effect sizes were numerically larger than those estimated from the HAM-D(17). Findings support that duloxetine 60 mg daily is the best effective dose. CONCLUSIONS: In this assessment of patients with MDD, the HAM-D(6) was shown to be more sensitive compared with the HAM-D(17) at detecting treatment effects. These findings are consistent with published results of other effective antidepressants.

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Curr Med Res Opin. 2006 Sep;22(9):1703-13.
A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder.
Munizza C, Olivieri L, Di Loreto G, Dionisio P.
Fourth Local Health Unit, Mental Health Department, Turin, Italy.

OBJECTIVES: To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression.Research design and methods: A total of 122 patients aged 19-64 years were enrolled in this multicenter, double-blind, double-dummy, randomized, comparator-controlled study. Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150-450 mg/day (n = 62) or sertraline 50-100 mg/day (n = 60).OUTCOME MEASURES: Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale (HAM-D), Montgomery Asberg Depression Rating Scale, Hamilton Anxiety Rating scale, and the Clinical Global Impression-Global Improvement/Severity scores; and by the rates of patients responding to treatment and considered to be in remission. Time to onset of efficacy and safety were assessed.RESULTS: Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission, and had similar onset times. In the Intent-to-Treat population, there were no significant differences in favor of trazodone at study endpoint in all efficacy measures, while a statistically significant difference was detected in the Per-Protocol population on HAM-D and in the percentage of responders. Analysis of HAM-D factors (anxiety/somatization, cognitive disturbance, retardation, and sleep disturbance) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint. Adverse drug reactions, mostly of mild intensity, were reported in 42% of trazodone-treated patients (mainly of the nervous system) and 43% of sertraline-treated patients (mainly gastrointestinal). One event was considered to be serious: a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized. Treatment was discontinued; the patient made a full recovery.CONCLUSIONS: This study showed that after 6 weeks, trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission. Tolerability profiles reflected the differing pharmacological properties of these antidepressants. Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances.

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J ECT. 2006 Sep;22(3):189-195.
Memory Performance in Severely Depressed Patients Treated by Electroconvulsive Therapy.
Hihn H, Baune BT, Michael N, Markowitsch H, Arolt V, Pfleiderer B.
>From the Departments of *Clinical Radiology and daggerPsychiatry, University of Munster, Munster; and double daggerDepartment of Psychology, University of Bielefeld, Bielefeld, Germany.

OBJECTIVES:: Depression is accompanied by disturbed implicit (unconscious) and explicit (conscious) memory functions. The aim was the assessment of immediate and delayed verbal and visual memory functions, concentration/attention during the course of electroconvulsive therapy (ECT) treatment. METHODS:: Twenty severely depressed, drug-treatment resistant, elderly patients were assessed with the Wechsler Memory Scale-Revised (WMS-R) before and at the end of the ECT series. RESULTS:: Patients revealed deficits in acquisition (immediate verbal and visual memory), attention/concentration, and retrieval of information (delayed memory) before ECT. After ECT, significant improvements were observed in immediate memory but not in delayed memory. Although higher total stimulation levels (millicoulombs) (P = 0.015) were associated with improvements in immediate visual memory, we found that longer duration of convulsions (P = 0.016) as well as lower levels of stimulation at last ECT (P = 0.036) were associated with improvements in immediate verbal memory. Moreover, we found that stimulation energy (millicoulombs) in total and at last ECT was the best predictor among several clinical and ECT parameters of improved visual memory and concentration and decreased verbal and general memory. CONCLUSIONS:: Prefrontal cortex-related memory processes, especially immediate memory encoding, improved after ECT, whereas long-term memory remained impaired, indicating that severely depressed patients remain cognitively inferior to normal subjects despite clinically successful treatment. This study may yield a better understanding of the time course of memory alterations in severely depressed patients receiving ECT. Improvement of immediate memory may be essential for establishing normal daily activities of life in the recovery phase of depression.

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J ECT. 2006 Sep;22(3):218-222.
Concomitant Use of Vagus Nerve Stimulation and Electroconvulsive Therapy for Treatment-resistant Depression.
Burke MJ, Husain MM.
>From the *Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, Wichita, KS; and daggerDepartment of Psychiatry, Southwestern Medical School, Dallas, TX.

OBJECTIVE:: This study explored the use of electroconvulsive therapy (ECT) in the pivotal study of vagus nerve stimulation (VNS) for treatment-resistant depression. METHODS:: The clinical characteristics and outcomes of study participants who received ECT during the first 12 months of VNS were compared with those who did not receive ECT. Physicians were instructed to turn off VNS during administration of ECT. RESULTS:: Of 205 (evaluable sample) patients who received VNS, 14 also received ECT. Participants who received ECT had a statistically significant greater number of hospital admissions (P = 0.037, Wilcoxon) and number of suicide attempts during their lifetimes (P= 0.022, Fisher exact test). Of 55 responders (>/=50% reduction in Hamilton Rating Scale for Depression-24 questions [HRSD-24] scores) after 12 months of VNS, 3 had received ECT. Of 32 remitters (HRSD-24 score, </=9), 2 had received ECT. Administration of ECT did not affect the implanted VNS device, and the presence of the implanted VNS device did not affect the administration of ECT. CONCLUSIONS:: Electroconvulsive therapy and VNS are not mutually exclusive. They can be used safely and effectively either sequentially or concurrently. Each can be prescribed as the depressive condition warrants-ECT for emergently worsening depressive symptoms and maintenance therapy and VNS for chronic, long-term therapy.

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J Affect Disord. 2006 Sep 7; [Epub ahead of print]
Interventions with depressed mothers and their infants: Modifying interactive behaviours.
Jung V, Short R, Letourneau N, Andrews D.
University of Alberta, Edmonton, AB, Canada.

BACKGROUND: Postpartum depression (PPD) has a prevalence ranging from 3% to 30% and is associated with serious infant growth and developmental problems. Interventions directed at improving maternal mood have been unsuccessful in producing changes in observed face-to-face interactions between mother and infant. The Keys to Caregiving (KTC) is an intervention program that helps parents to understand and respond to infant behaviours, with a goal of increasing positive affective expressions in infants. In this pilot study, KTC was used with mothers suffering from mild to moderate PPD and their infants. METHODS: PPD was confirmed by scores on the Edinburgh Postnatal Depression Scale and the Beck Depression Inventory. Eleven dyads completed the study. KTC was carried out in 5 weekly group sessions, beginning at infant age of 3 months. Dyads were videotaped prior to and after KTC, using the Face-to-Face Still-Face paradigm, which assesses infants' responses during normal play and the effects of the Still-Face perturbation. The tapes were scored for infant facial emotion expressions. RESULTS: After intervention, infants displayed a marked increase in Interest and Joy when interacting face-to-face with their mothers, even though mothers' depression ratings did not change. LIMITATIONS: This pilot study is limited by lack of control dyads, however, it provides the foundation necessary for a full trial. CONCLUSIONS: This study suggests that intervention that focuses on what mothers do with their infants instead of how they feel can be effective in increasing infants' positive responsiveness and improving infant outcomes. Such interventions can be an essential component of treatment when mothers present with postpartum depression.

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Prog Neuropsychopharmacol Biol Psychiatry. 2006 Sep 6; [Epub ahead of print]
Quetiapine in combination with citalopram in patients with unipolar psychotic depression.
Konstantinidis A, Hrubos W, Nirnberger G, Windhager E, Lehofer M, Aschauer H, Kasper S.
Department of General Psychiatry, Medical University Vienna, Austria.

This 6-week, open-label, multicenter study evaluated the efficacy and safety of quetiapine in combination with citalopram in adult patients (n=25) with ICD-10/DSM-IV unipolar psychotic depression. The primary endpoint was change from baseline to Week 6 in the Hamilton Depression Rating Scale (HAM-D-21) score. Secondary endpoints were change from baseline to Week 6 in the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale scores. Spontaneously reported adverse events (AEs), the Simpson Angus Scale (SAS), and the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale scores were recorded. Patients' average age was 51.4 years and baseline weight was 72.6 kg. Quetiapine (50-750 mg/day, mean dose+/-SD: 303+/-118 mg/day), in combination with citalopram (20-60 mg/day, mean dose+/-SD: 34+/-12 mg/day), provided significant improvements in depression. Mean (+/- SD) HAM-D-21 was reduced to 13.25+/-10.87 at Week 6 from a baseline value of 31.21+/-5.18. Significant improvement of psychotic symptoms (mean+/-SD) was indicated by the decrease from baseline (59.25+/-6.60) to Week 6 (35.25+/-15.60) in BPRS scores. No serious AEs occurred. The mean change in weight was +2.1 kg. Mean (+/- SD) weight at visit 1 was 72.72 (+/-16.34) kg and mean (SD) weight at visit 4 was 74.79 (+/-18.69) kg. Quetiapine in combination with citalopram appears to be effective and is well tolerated in the treatment of unipolar psychotic depression. Further studies of larger, double-blind, parallel-group design are warranted to confirm these findings.

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Int J Neuropsychopharmacol. 2006 Sep 7;:1-12 [Epub ahead of print]
A randomized trial of low-frequency right-prefrontal-cortex transcranial magnetic stimulation as augmentation in treatment-resistant major depression.
Fitzgerald PB, Huntsman S, Gunewardene R, Kulkarni J, Daskalakis ZJ.
Alfred Psychiatry Research Centre, The Alfred and Monash University Department of Psychological Medicine, Melbourne, Victoria, AustraliaThe Victoria Clinic, Prahran, Melbourne, Australia.

Low-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) appears to have antidepressant properties although the effectiveness of this treatment in clinical practice has not been assessed nor have the optimal stimulation parameters been adequately defined. A total of 130 patients with treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over the right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk extension. Non- responders were randomized to either 5- or 10-Hz left PFC rTMS. Overall, 66 patients (51%) achieved response and 35 (27%) remission criteria. For right-sided treatment, depression significantly improved but there was no between-group difference. Twenty-eight (42%) patients in the 1-Hz group and 33 (53%) patients in the 2-Hz group achieved response criteria (chi2=1.40, p>0.05). Depression symptom scores also improved for patients who crossed over to left-sided treatment but there was no significant difference in response between 5- and 10-Hz rTMS. Despite a heterogeneous sample, a significant proportion of patients met clinical response criteria following treatment but response to 1 and 2 Hz did not differ. 2-Hz right PFC rTMS has antidepressant properties but offers no advantage over 1 Hz despite doubling pulse number.

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J Clin Psychiatry. 2006 Aug;67(8):1266-71.
Outcome of a 4-step treatment algorithm for depressed inpatients.
Birkenhager TK, van den Broek WW, Moleman P, Bruijn JA.
>From the Department of Psychiatry, Erasmus Medical Centre, Rotterdam (Drs. Birkenhager, van den Broek, and Bruijn); and Moleman Psychopharmacology, Amerongen (Dr. Moleman), The Netherlands.

OBJECTIVE: The aim of this study was to examine the efficacy and the feasibility of a 4-step treatment algorithm for inpatients with major depressive disorder. METHOD: Depressed inpatients, meeting DSM-IV criteria for major depressive disorder, were enrolled in the algorithm that consisted of sequential treatment steps (washout period, anti-depressant monotherapy, lithium addition, treatment with a nonselective monoamine oxidase inhibitor, electroconvulsive therapy). Definition of nonresponse and progression through the steps of the algorithm was dependent on the score on the 17-item Hamilton Rating Scale for Depression (HAM-D) at predefined evaluation times. Patients were admitted from April 1997 through July 2001. RESULTS: Of the 203 patients studied, 149 were treated according to the full algorithm, and 54 patients were immediately entered into step 3. Of the 203 patients, 165 (81%) achieved response (>/= 50% reduction in HAM-D score) and 101 (50%) remitted (final HAM-D score </= 7). Of the 149 patients treated according to the full algorithm, 129 (87%) responded and 89 (60%) remitted. Twenty-four patients (16%) dropped out from the algorithm. CONCLUSION: Although response with antidepressant monotherapy was less than 50%, successive treatment according to the 4-step algorithm was very effective in a sample of depressed inpatients. The adherence to the algorithm was good as shown by a low dropout rate. This study emphasizes the importance of persisting with standardized antidepressant treatment in patients who are initially nonresponders to the first antidepressant. By the end of the study, more than 80% of the patients responded and 50% achieved full remission.

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Prim Care Companion J Clin Psychiatry. 2006;8(4):212-219.
The Safety and Tolerability of Duloxetine Compared With Paroxetine and Placebo: A Pooled Analysis of 4 Clinical Trials.
Nelson JC, Lu Pritchett Y, Martynov O, Yu JY, Mallinckrodt CH, Detke MJ.
Department of Psychiatry, University of California at San Francisco, San Francisco ; Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Ind. ; Department of Psychiatry, Indiana University School of Medicine, Indianapolis ; Department of Psychiatry, McLean Hospital, Belmont, Mass. ; and Department of Psychiatry, Harvard Medical School, Boston, Mass. . Dr. Pritchett is now with Abbott Laboratories, Abbott Park, Ill., and Dr. Martynov is now with Amylin Pharmaceuticals, Inc., San Diego, Calif.

Background: To compare the safety and tolerability of duloxetine with paroxetine and placebo in patients with major depressive disorder (MDD).Method: Data from four 8-week randomized, double-blind, placebo- and paroxetine-controlled studies of duloxetine for MDD (DSM-IV criteria) were pooled to compare the safety and tolerability of duloxetine 40 to 120 mg/day with paroxetine 20 mg q.d. Two of the 4 trials included a 26-week extension.Results: The pooled database included 1466 patients (duloxetine, N = 736; paroxetine, N = 359; placebo, N = 371). No deaths occurred in the acute phase trials. Discontinuation rates for adverse events did not differ significantly for duloxetine, 8.0%, and paroxetine, 6.1%. Nausea was the most frequent treatment-emergent adverse event for duloxetine (duloxetine, 14.4%; paroxetine, 12.0%; placebo, 3.8%). Blood pressure and corrected QT (QTc) interval changes were modest and did not differ significantly for the 3 groups. Mean heart rate increased slightly in the duloxetine group, 1.0 beat/minute, and did differ significantly (p < .001) from that in the paroxetine group, but the change is of doubtful importance. Mean changes in laboratory analytes remained within the reference range. Emergent sexual dysfunction was significantly greater among duloxetine- and paroxetine-treated patients than placebo-treated patients (p = .007 vs. duloxetine and p < .001 vs. paroxetine); however, it was significantly lower in duloxetine-treated patients than in paroxetine-treated patients (46.4% vs. 61.4%; p = .015). During the extension phase, weight gain (>/= 7% of initial body weight) was greater in both active-treatment groups than in the placebo group (duloxetine, 10.8%; paroxetine, 13.8%; placebo, 3.1%), but the active-treatment groups did not differ.Conclusions: Duloxetine is safe and well tolerated in patients with MDD, with safety and tolerability comparable to that of paroxetine.

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Depress Anxiety. 2006 Jul 14; [Epub ahead of print]
Intensive Short-Term Dynamic Psychotherapy of treatment-resistant depression: A pilot study.
Abbass AA.
Associate Professor and Director of Education, Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.

This pilot study examined the effectiveness of Intensive Short-term Dynamic Psychotherapy (ISTDP) in treatment-resistant depression (TRD). Ten patients with TRD were provided a course of ISTDP. Clinician and patient symptom and interpersonal measures were completed every 4 weeks, at termination, and in follow-up. Medication, disability, and hospital costs were compared before and after treatment. After an average of 13.6 sessions of therapy, all mean measures reached the normal range, with effect sizes ranging from 0.87 to 3.3. Gains were maintained in follow-up assessments. Treatment costs were offset by cost reductions elsewhere in the system. This open study suggests that ISTDP may be effective with this challenging patient group. A randomized, controlled trial and qualitative research are warranted to evaluate this treatment further and to examine its possible therapeutic elements. Depression and Anxiety 0:1-4, 2006. (c) 2006 Wiley-Liss, Inc.

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Depress Anxiety. 2006 Jul 14; [Epub ahead of print]
Lamotrigine adjunctive treatment in resistant unipolar depression: An open, descriptive study.
Gabriel A.
Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.

Adjunctive treatment of lamotrigine compared to other antidepressants in the treatment of partially responsive, poorly functioning patients with unipolar depression was assessed. Fourteen consenting patients with confirmed DSM-IV-R diagnosis of unipolar depression were identified as treatment resistant. All patients failed at least two 8-week treatment trials with antidepressants. All were treated with lamotrigine as an adjunct to other antidepressants for at least 6 months. The primary effectiveness measure was the Clinical Global Impression Severity subscale (CGI-S). Other scales included the Montgomery-Asberg Depression Scale (MADRS) and the Global Assessment of Functioning Scale (GAF). Monitoring for skin rashes, headache, dizziness, somnolence, and gastrointestinal disturbances was carried out to assess for adverse events. Baseline measures prior to adding lamotrigine were compared to those at 8 weeks and 6 months with adjunctive treatment. Twelve patients of the total (n=14) completed the trial, and two discontinued treatment. There was significant, rapid, and robust resolution in symptoms in all effectiveness measures, including the core symptoms of depression, as shown by the changes from baseline in CGI-S, and MADRS at 8 weeks. Social and occupational functioning was significantly improved at 6 months. Eight patients returned to gainful employment or started schooling. Patients tolerated the adjunctive lamotrigine treatment well. Lamotrigine may have antidepressant properties in patients with unipolar depression and may have an earlier onset of action when given in combination with antidepressants. Depression and Anxiety 0:1-4, 2006. (c) 2006 Wiley-Liss, Inc.

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Depress Anxiety. 2006 Jul 14; [Epub ahead of print]
Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation.
Wohlreich MM, Mallinckrodt CH, Prakash A, Watkin JG, Carter WP.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.

Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. To further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This single-arm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age >/=18 years) meeting DSM-IV criteria for MDD (n=128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (P<.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by >10% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of 3.1 kg over 2 years of treatment. Results from this study suggest that rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable. Despite weekly escalation, the majority of adverse events were mild and transient and occurred in the first week of duloxetine dosing (at 60 mg once daily). Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of TEAEs and treatment discontinuation due to adverse events. Time course profiles of body weight and heart rate showed modest increases during 2 years of treatment [ClinicalTrials.gov number, NC T000 42575]. Depression and Anxiety 0:1-12, 2006. (c) 2006 Wiley-Liss, Inc.

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J Clin Psychiatry. 2006 Jun;67(SUPPLEMENT 6):16-22.
Treatment-Resistant Depression.
Souery D, Papakostas GI, Trivedi MH.
>From the Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium (Dr. Souery); the Department of Psychiatry, Massachusetts General Hospital, Boston (Dr. Papakostas); and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Dr. Trivedi).

Treatment-resistant depression (TRD) is a common clinical occurrence among patients treated for major depressive disorder. However, a clear consensus regarding the criteria defining TRD is lacking in the psychiatric community. Many patients who are considered treatment resistant are actually mis-diagnosed or inadequately treated. Clinicians need to accurately diagnose TRD by examining primary and secondary (organic) causes of depression and acknowledging paradigm failures that contribute to a misdiagnosis of TRD. A correct determination of what constitutes TRD requires consensus on criteria of treatment response (i.e., dose, duration, and compliance) and on the number of adequate trials required before a patient is determined to be nonresponsive. Additionally, clinical validation of available staging models needs to be completed. While several studies have identified predictors of non-response, clinical studies investigating the predictors of resistance following the failure of 2 or more antidepressant trials should be pursued. In managing TRD, 3 pharmacotherapy strategies are in clinical use: optimization of antidepressant dose, augmentation/combination therapies, and switching therapies. However, the optimal strategy for treating TRD has yet to be identified. Therefore, further controlled clinical trials are essential to identify the most effective treatment strategies.

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J Clin Psychiatry. 2006 Jun;67 Suppl 6:3-8.
The role of dopamine and norepinephrine in depression and antidepressant treatment.
Nutt DJ.
>From Psychopharmacology Unit, School of Medical Sciences, University of Bristol, Bristol, U.K.

Most antidepressants in use today are descendants of the monoamine oxidase inhibitor iproniazid and the tricyclic agent imipramine. These agents were both originally developed for other indications but then were serendipitously determined to have antidepressant effects. Elucidation of the mechanisms of action of these first antidepressants, along with those of reserpine and amphetamine, led to the monoamine theories of depression. Through the past several decades, approaches undertaken to clarify the roles of the neurotransmitters norepinephrine, dopamine, and serotonin in depression have included animal studies, human biological and postmortem studies, inferences drawn from antidepressant drug actions, and challenge or depletion studies; most recently, brain imaging studies have proved to be especially informative. This research has identified novel potential targets, with the goal of developing new antidepressant drugs with better efficacy and faster onset of action than current "gold-standard" treatments.

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J Clin Psychiatry. 2006 Jun;67(6):865-873.
Extended-Release Bupropion for Patients With Major Depressive Disorder Presenting With Symptoms of Reduced Energy, Pleasure, and Interest: Findings From a Randomized, Double-Blind, Placebo-Controlled Study.
Jefferson JW, Rush AJ, Nelson JC, Vanmeter SA, Krishen A, Hampton KD, Wightman DS, Modell JG.
>From Madison Institute of Medicine, Madison, Wis. (Dr. Jefferson); the Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas (Dr. Rush); the Department of Psychiatry, University of California, San Francisco (Dr. Nelson); and the Neurosciences Medicine Development Center, GlaxoSmithKline, Research Triangle Park, N.C. (Drs. VanMeter and Modell, Messrs. Krishen and Hampton, and Ms. Wightman).

OBJECTIVE: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of extended-release bupropion (bupropion XL) in the treatment of major depressive disorder (MDD) with prominent symptoms of decreased energy, pleasure, and interest. METHOD: Eligible adult outpatients meeting DSM-IV criteria for MDD were randomly assigned to bupropion XL 300 to 450 mg/day (N = 135) or placebo (N = 139) for 8 weeks. The primary efficacy measure, change from baseline on the 30-item Inventory of Depressive Symptomatology-Self Report (IDS-IVR-30) total score, was obtained using interactive voice response (IVR) technology. Secondary measures included change from baseline on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C-30) total score and change in domain subset scores for energy, pleasure, and interest; for insomnia; and for anxiety. Response and remission rates were also calculated. Safety was assessed by withdrawal rates, adverse events (AEs), body weight, and vital signs. The study was conducted from June 24, 2003, to June 30, 2004. RESULTS: Bupropion XL was superior to placebo at endpoint in reducing the IDS-IVR-30 total score (p = .018) and the energy, pleasure, and interest domain (p = .007) and the insomnia domain (p = .023) scores. IDS-C-30 outcomes were also significant (p < .001; p < .001, and p = .008, respectively). Clinician-rated remission rates were significantly higher with bupropion XL than placebo (32% vs. 18%, IDS-C-30; 41% vs. 27%, IDS-IVR-30), as were response rates (50% vs. 35%, IDS-C-30; 53% vs. 38%, Clinical Global Impressions-Improvement of Illness). Most AEs were mild or moderate. The incidence of a >/= 7% body weight loss was 3.7% with bupropion XL and 1.4% with placebo. CONCLUSION: Bupropion XL was effective and well tolerated in MDD patients with decreased energy, pleasure, and interest.

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J Clin Psychiatry. 2006 Jun;67(6):850-864.
Are All Antidepressants Really the Same? The Case of Fluoxetine: A Systematic Review.
Cipriani A, Barbui C, Brambilla P, Furukawa TA, Hotopf M, Geddes JR.
>From the Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy (Drs. Cipriani and Barbui); Department of Pathology and Experimental & Clinical Medicine, Section of Psychiatry, University of Udine, Udine, Italy (Dr. Brambilla); Department of Psychiatry, Nagoya City University Medical School, Nagoya, Japan (Dr. Furukawa); Department of Psychological Medicine, Institute of Psychiatry, London, United Kingdom (Dr. Hotopf); and the Department of Psychiatry, University of Oxford, Oxford, United Kingdom (Dr. Geddes).

OBJECTIVE: To systematically review the efficacy and tolerability of fluoxetine, the most widely studied of newer antidepressants, in comparison with all other antidepressants in the acute treatment of depression in patients aged more than 18 years. DATA SOURCES: Studies were identified through electronic searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2004. The terms FLUOXETIN* OR adofen or docutrix or erocap or fluctin or fluctine or fluoxeren or fontex or ladose or lorien or lovan or mutan or prozac or prozyn or reneuron or sanzur or saurat or zactin were used. MEDLINE (1966-2004) and EMBASE (1974-2004) were searched using fluoxetine and randomized controlled trial or random allocation or double-blind method. No language restrictions were applied. Reference lists of relevant papers and previous systematic reviews were hand-searched for published reports up to March 2004. STUDY SELECTION: Only randomized controlled trials (either blind or nonblind) were included. DATA SYNTHESIS: 131 randomized controlled trials were eligible. A p value less than .01 was chosen to test the null hypothesis, and a 99% confidence interval was calculated to detect statistically significant differences with a high degree of confidence. Fixed- and random-effects relative risks, odds ratios (ORs), and Peto ORs were routinely calculated for each outcome measure. In terms of efficacy, we found a statistically significant difference favoring sertraline and venlafaxine over fluoxetine. In terms of tolerability, patients allocated to fluoxetine were less likely to leave the study early only in comparison with those allocated to amitriptyline and pramipexole. CONCLUSIONS: This systematic review highlighted that there are differences between fluoxetine and specific comparator antidepressants. Several of the differences met a prespecified criterion for clinical significance. The statistical approach adopted in this systematic review could represent a useful tool for putting clinical trial data into practice.

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Int Clin Psychopharmacol. 2006 Mar;21(2):105-10.
Onset of action of escitalopram compared with other antidepressants: results of a pooled analysis.
Kasper S, Spadone C, Verpillat P, Angst J.
aDepartment of General Psychiatry, Medical University of Vienna, Vienna, Austria bHopital Saint-Louis Paris, France cH. Lundbeck A/S, Paris, France dZurich University Psychiatric Hospital, Zurich, Switzerland.

In general, antidepressant drugs are regarded as too slow acting. Most patients who benefit from treatment require more than 2 weeks of therapy to respond to treatment. An efficacious and well-tolerated antidepressant drug with an earlier onset of effect would be of greater interest to clinicians and patients. To study the onset of effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), data were pooled from controlled randomized clinical double-blind trials comparing this drug with other antidepressant drugs (SSRIs and venlafaxine XR) in major depressive disorder (MDD), with assessments of the primary efficacy parameter [mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline, using last observation carried forward]. The mean change in MADRS total scores was significantly higher for escitalopram-treated patients than for patients treated with the comparators on day 7 (-3.9 versus -3.4, respectively, P=0.029). This difference remained significant and in favour of escitalopram at all subsequent assessments. Using secondary outcomes (Clinical Global Impression of Improvement and Severity scales and early improvement), the results consistently showed a statistically significantly faster onset of effect of escitalopram compared to other antidepressants. In conclusion, by using the MADRS scale and pooling data from the escitalopram clinical trials in MDD comparing escitalopram with other active antidepressant drugs, escitalopram was shown to be a fast-acting antidepressant with a more rapid onset of effect than the comparators, particularly other SSRIs.

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J Clin Psychopharmacol. 2006 Feb;26(1):75-78.
Mirtazapine Orally Disintegrating Tablets Versus Venlafaxine Extended Release: A Double-blind, Randomized Multicenter Trial Comparing the Onset of Antidepressant Response in Patients With Major Depressive Disorder.
Benkert O, Szegedi A, Philipp M, Kohnen R, Heinrich C, Heukels A, van der Vegte-Senden M, Baker RA, Simmons JH, Schutte AJ.
*PAS, Nurnberg, Germany; daggerCharite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Germany;; double daggerOrganon International, Roseland, NJ; section signBezirkskrankenhaus Landshut, Germany; parallelIMEREM GmbH, Nurnberg, Germany; and; paragraph signNV Organon, Oss, The Netherlands.

This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of >/=50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of </=7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties.

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J Clin Psychopharmacol. 2006 Feb;26(1):56-60.
A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder.
Papakostas GI, Perlis RH, Scalia MJ, Petersen TJ, Fava M.
Depression Clinical and Research Program, Massachusetts General Hospital,Harvard Medical School, Boston, MA.

CONTEXT:: Pattern analysis suggests that "true" drug response is characterized by clinical improvement that is not subsequently followed by a worsening of symptoms (sustained clinical response). To date, several reports demonstrate that early response rates are equivalent between antidepressant-treated and placebo-treated groups of patients with major depressive disorder, suggesting that patients who demonstrate significant and sustained symptom improvement during the first 2 weeks of treatment are not responding to the antidepressant itself, but to nonspecific, placebo-like factors. OBJECTIVE:: To compare early sustained response rates between antidepressant- and placebo-treated adults with major depressive disorder. DATA SOURCES:: Medline/Pubmed were searched. No year of publication limits were used. STUDY SELECTION:: Randomized, double-blind, placebo-controlled antidepressant trials or pooled reports/meta-analyses of such trials reporting early sustained response rates for major depressive disorder. The decision to include studies in the meta-analysis was performed by 2 reviewers. DATA EXTRACTION:: Data were extracted with the use of a precoded form. DATA SYNTHESIS:: Analyses were performed on the proportion of patients who achieved a sustained response the first 2 weeks of treatment, as well as the first week of treatment. A random-effects model with fixed drug effects was used to combine the studies and make comparisons of sustained early response rates between antidepressant- and placebo-treated groups. Data from 8 reports involving a total of 7121 major depressive disorder patients (4076 randomized to treatment with an antidepressant and 3045 randomized to placebo) were analyzed. Antidepressant-treated patients were more likely to demonstrate sustained clinical response by 2 weeks (odds ratio 2.06, 95% CI: 1.52-2.8) or 1 week of treatment (odds ratio 1.50, 95% CI: 1.08-2.08) than placebo-treated patients. CONCLUSIONS:: The results of the present analysis suggest that "true" drug response can occur the first 2 week as well as the first week of treatment of major depressive disorder with conventional antidepressants.

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J Clin Psychopharmacol. 2006 Feb;26(1):13-20.
Sertraline Treatment of Co-occurring Alcohol Dependence and Major Depression.
Kranzler HR, Mueller T, Cornelius J, Pettinati HM, Moak D, Martin PR, Anthenelli R, Brower KJ, O'malley S, Mason BJ, Hasin D, Keller M.
*Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT; daggerSouthern Arizona VA Health Care System, Department of Psychiatry, University of Arizona School of Medicine, Tucson, AZ; double daggerDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA; section signDepartment of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA; parallelDepartment of Psychiatry, Medical University of South Carolina, Charleston, SC; paragraph signDepartment of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN; #Department of Psychiatry, University of Cincinnati School of Medicine, Cincinnati, OH; **Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, MI; daggerdaggerDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT; double daggerDagger;Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA; section sign section signDepartment of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY; and parallel parallelDepartment of Psychiatry, Brown University School of Medicine, Providence, RI.

BACKGROUND:: Major depressive disorder occurs commonly in association with alcohol dependence, both in clinical samples and in the community. Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results. This multicenter, double-blind, placebo-controlled trial of sertraline was designed to address many of the potential methodological shortcomings of studies of co-occurring disorders. METHOD:: Following a 1-week, single-blind, placebo lead-in period, 328 patients with co-occurring major depressive disorder and alcohol dependence were randomly assigned to receive 10 weeks of treatment with sertraline (at a maximum dose of 200 mg/d) or matching placebo. Randomization was stratified, based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking, resulting in a sample of 189 patients with Hamilton Depression Rating Scale scores >/=17 (group A) and 139 patients with Hamilton Depression Rating Scale scores </=16 (group B). RESULTS:: Both depressive symptoms and alcohol consumption decreased substantially over time in both groups. There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients. CONCLUSION:: Despite careful attention to methodological considerations, this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence. The high rate of response among placebo-treated patients may help to explain these findings. Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders.

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Lancet. 2006 Jan 14;367(9505):153-67.
Recent developments and current controversies in depression.
Ebmeier KP, Donaghey C, Steele JD.
Division of Psychiatry, University of Edinburgh, Kennedy Tower, Morningside Park, Edinburgh, UK. k.ebmeier@ed.ac.uk

In this review of the last 5 years' developments in research into depression we focus on recent advances and current controversies. We cover epidemiology and basic science as well as the treatment of depression in adults in all its forms. Depression in , as well as in has been covered in recent Seminars in The Lancet. Depression in adulthood remains a very common and under-treated condition, resulting in a high degree of disability. Increasingly detailed knowledge about impairment of information processing in depression is being supplemented by quantitative studies of the brain processes underlying these impairments. Most patients improve with present treatments. The mechanisms of action of antidepressants are not fully understood; the hypothesis that reversing hippocampal cell loss in depression may be their active principle is a fascinating new development. Moral panic about the claim that antidepressant serotonin reuptake inhibitors cause patients to commit suicide and become addicted to their medication may have disconcerted the public and members of the medical profession. We will try to describe the considerable effort that has gone into collecting evidence to enlighten this debate.

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Med Hypotheses. 2006 Jan 10; [Epub ahead of print]
Chlorpheniramine, selective serotonin-reuptake inhibitors (SSRIs) and over-the-counter (OTC) treatment.
Hellbom E.
Saningsvagen 86, S-17552 Jarfalla, Sweden.

Some old antihistamines were selective serotonin-reuptake inhibitors (SSRIs) and the SSRI effect was discovered by Nobel Laureate Professor Arvid Carlsson as early as 1969. Chlorpheniramine was the most active of the tested drugs, and it compares favourably with amitriptyline and imipramine with respect to actions on both serotonergic and noradrenergic neurons. Chlorpheniramine can be called a SSRI, since the blocking of 5HT is stronger than the effect on noradrenaline neurons; however it might also be called a selective serotonin and noradrenaline reuptake inhibitor (SSNRI) and be compared with new drugs, such as venlafaxine. Carlsson suggested the potential value of clinical studies of the antidepressant properties of this and related antihistamine drugs. But, in the event, no such trials were ever performed at the time. However, later clinical observations of the benefits of dex-chlorpheniramine treatment in panic disorder have been published. Clinical experience suggests that patients using chlorpheniramine, and having also a concomitant depression or panic disorder, may experience a return of symptoms when their old drug is changed to a new antihistamine lacking SSRI effects. Yet this phenomenon is not known to many doctors, and even less known to the large number of patients buying chlorpheniramine under various trade names over-the-counter (OTC) at a low price for self-treatment of hay fewer or as a cold remedy. Chlorpheniramine was introduced in USA under the name Chlor-Trimeton as long ago as July 1950, and is still on the market. Therefore, this SSRI is now over 50 years old. If chlorpheniramine had been tested in depression in the nineteen seventies, it is probable that a safe, inexpensive SSRI drug could have been used some 15 years earlier than fluoxetine - which became available in 1987. Chlorpheniramine might have been the first safe, non-cardiotoxic and well-tolerated antidepressant. Billions of dollars in the development and marketing costs would have been saved, and the suffering of millions of patients alleviated.

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Am Fam Physician. 2006 Jan 1;73(1):83-6.
Cognitive therapy for depression.
Rupke SJ, Blecke D, Renfrow M.
Michigan State University College of Human Medicine, East Lansing, Michigan, USA. srupke@synergymedical.org

Cognitive therapy is a treatment process that enables patients to correct false self-beliefs that can lead to negative moods and behaviors. The fundamental assumption is that a thought precedes a mood; therefore, learning to substitute healthy thoughts for negative thoughts will improve a person's mood, self-concept, behavior, and physical state. Studies have shown that cognitive therapy is an effective treatment for depression and is comparable in effectiveness to antidepressants and interpersonal or psychodynamic therapy. The combination of cognitive therapy and antidepressants has been shown to effectively manage severe or chronic depression. Cognitive therapy also has proved beneficial in treating patients who have only a partial response to adequate antidepressant therapy. Good evidence has shown that cognitive therapy reduces relapse rates in patients with depression, and some evidence has shown that cognitive therapy is effective for adolescents with depression.

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Biol Psychiatry. 2006 Jan 7; [Epub ahead of print]
Pharmacotherapy of Depressed Children and Adolescents: Current Issues and Potential Directions.
Vasa RA, Carlino AR, Pine DS.
Johns Hopkins University School of Medicine (RAV, ARC).

The recent deliberations by the U.S. Food and Drug Administration (FDA) regarding the relationship between antidepressants and suicidality in children have incited debates about the safety of these medications for the treatment of pediatric depression. In light of these events, this review discusses four issues pertaining to pharmacotherapy for pediatric depression. First, we summarize pertinent data from randomized controlled trials of antidepressants for pediatric depression. These data provide strong support for fluoxetine and modest support for the other antidepressants. Second, we examine the outcome of the FDA meta-analysis of the data on antidepressant-induced suicidality, with specific emphasis on the methodological limitations of this analysis. Third, we consider the collective implications of the antidepressant efficacy and suicidality data on clinical practice. Specifically, we present several compelling arguments that justify the continued use of antidepressants for pediatric depression, despite the inherent limitations of these medications. Finally, we review several pathophysiological factors that might provide insights into treatment response and impact the design of future pharmacotherapy studies of depression. These factors relate to diagnostic heterogeneity, developmental consistency, and psychobiology. Potentially novel pharmacotherapies are also discussed.

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Psychol Aging. 2005 Dec;20(4):601-9.
Treatment of depression in low-income older adults.
Arean PA, Gum A, McCulloch CE, Bostrom A, Gallagher-Thompson D, Thompson L.
Department of Psychiatry, University of California, San Francisco, CA, US. pata@lppi.ucsf.edu.

The purpose of this study was to compare cognitive-behavioral group therapy (CBGT), clinical case management (CCM), and their combination (CBGT + CCM) to treat depression in low-income older adults (60+). Sixty-seven participants with major depressive disorder or dysthymia were randomly assigned and entered into 1 of the 3 treatment conditions for 6 months. They were followed for 18 months after treatment initiation on depression and functional outcomes. CCM and CBGT + CCM led to greater improvements in depressive symptoms than CBGT, but CBGT led to greater improvements in physical functioning. All 3 conditions resulted in similar reduction of needs. Findings suggest that disadvantaged older adults with depression benefit from increased access to social services either alone or combined with psychotherapy. ((c) 2006 APA, all rights reserved).

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J Clin Psychiatry. 2005 Nov;66(11):1376-85.
Typical and atypical antipsychotics in bipolar depression.
Gao K, Gajwani P, Elhaj O, Calabrese JR.
>From the Department of Psychiatry, University Hospitals of Cleveland, Case Western Reserve University, School of Medicine, Cleveland, Ohio.

BACKGROUND: Symptomatic bipolar patients experience more depressive than manic symptoms, but fewer studies have been designed for bipolar depression than for bipolar mania. Since the antipsychotic agents have been shown to diminish depressive symptoms during the treatment of mania, atypical agents are now being studied for use in bipolar depression. DATA SOURCES: English-language articles published from 1980 through July 2004 and cited in MEDLINE were searched using the keywords antipsychotics, typical antipsychotics, atypical antipsychotics, bipolar depression, bipolar disorder, manic-depressive illness, placebo, and clinical trial. The generic and brand names of individual antipsychotics were also entered as keywords. Peer-reviewed abstracts of placebo-controlled studies assessing acute or long-term efficacy in bipolar depression presented at major scientific meetings were also reviewed. STUDY SELECTION: Use of a depression rating scale was required for inclusion of studies of the atypical antipsychotic agents in our analysis. DATA SYNTHESIS: Twenty-one randomized trials and 13 nonrandomized prospective trials were identified. In the only 2 acute, double-blind, placebo-controlled studies of antipsychotics in bipolar depression, the effect size of olanzapine was small (0.32) compared with the effect sizes of quetiapine (0.91-1.09, depending on dose). The effect size in acute mania of olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39, respectively. Both olanzapine and quetiapine have been shown to be superior to placebo in the acute treatment of bipolar I depression. In addition, olanzapine has been shown to be more effective than placebo in delaying relapse into bipolar depression. With the exception of a 6-month perphenazine study, there are no other randomized studies of typical antipsychotics that support the conclusion that this class of medication worsens bipolar depression. CONCLUSION: Emerging data suggest that the atypical antipsychotic agents have a role in the acute and long-term treatment of bipolar depression. No convincing data support the impression that the typical antipsychotic agents worsen bipolar depression.

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Behav Res Ther. 2005 Oct 3; [Epub ahead of print]
Naturalistic outcome of case formulation-driven cognitive-behavior therapy for anxious depressed outpatients.
Persons JB, Roberts NA, Zalecki CA, Brechwald WA.
Psychology Department, San Francisco Bay Area Center for Cognitive Therapy, University of California, 5435 College Avenue, Oakland, CA 94618, Berkeley, USA.

This article describes a case formulation-driven approach to the treatment of anxious depressed outpatients and presents naturalistic outcome data evaluating its effectiveness. Fifty-eight patients who received case formulation-driven cognitive-behavior therapy (CBT) in a private practice setting were studied. All received individual CBT guided by a case formulation and weekly outcome monitoring; in addition, 40 patients received adjunct therapies, including pharmacotherapy, which were added as indicated by the case formulation and the results of weekly outcome monitoring. Patients treated with case formulation-driven CBT showed statistically and clinically significant changes in anxiety and depression that were generally comparable to those reported in published randomized controlled trials of empirically supported therapies (ESTs) for single mood and anxiety disorders. Findings support the proposal that anxious depressed patients who have multiple comorbidities and require multiple therapies can benefit from empirically supported treatments guided by a case formulation and weekly outcome monitoring.

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Nord J Psychiatry. 2005;59(3):173-8.
Modafinil augmentation in depressed patients with partial response to antidepressants: a pilot study on self-reported symptoms covered by the Major Depression Inventory (MDI) and the Symptom Checklist (SCL-92).
Rasmussen NA, Schroder P, Olsen LR, Brodsgaard M, Unden M, Bech P.
Psychiatric Research Unit, Frederiksborg General Hospital, Dyrehavevej, Hillerod, Denmark.

Treatment-resistant depression, i.e. partial or non response to antidepressants in spite of various treatment attempts with optimized doses and combinations, is rather common. With residual symptoms such as tiredness, anhedonia and concentration disturbances, the treatment strategy has often been to use monoamino-oxidase inhibitors (MAOIs). Their use, however, is limited due to interaction problems. Modafinil is recently developed wake-promoting drug with only minor side-effects. Pilot studies indicate that it appears to have an augmentation effect in treatment-resistant depression. This open-label study performed in the private psychiatric practice setting is the first to make a comprehensive evaluation of the target patient profile based on patient-reported symptoms. Modafinil in doses of 100-400 mg was administered as augmentation to ongoing antidepressant therapy in patients with partial response and suffering from hypersomnia. The total number of patients was 21 and 43% of these were responders (i.e. had a score reduction of >50% on the Major Depression Inventory (MDI) as well as remitters, i.e. the remission rate was 43%. At endpoint, the responders had psychological distress scores on the Symptom Checklist (SCL-92) on the level of the general Danish population. Baseline characteristics for responders were lower scores on depression, hostility, anxiety, somatization, obsession and psychoticism. Modafinil thus appears to be an appropriate augmentation to antidepressant treatment, leading to a remission rate of 43%. However, the results from this open-label study need ot be confirmed in a placebo-controlled trial.

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J Psychopharmacol. 2005 Oct 4; [Epub ahead of print]
Resolution of sexual dysfunction during double-blind treatment of major depression with reboxetine or paroxetine.
Baldwin DS, Bridgman K, Buis C.
Clinical Neuroscience Division, School of Medicine, University of Southampton, Southhampton, UK.

The selective noradrenaline re-uptake inhibitor reboxetine may have advantages over the selective serotonin re-uptake inhibitors fluoxetine and citalopram, in effects on sexual function and satisfaction. The effects of reboxetine and paroxetine on sexual function were compared by examining data from the UK centres in an international double-blind flexible-dose parallel-group multi-centre randomized controlled trial of acute treatment of patients with DSM-IV major depression. Patients were randomly assigned to receive reboxetine (4 mg b.d.) or paroxetine (20 mg mane) using a double-dummy technique to preserve the blind. The dosage could be increased at day 28 (to reboxetine 4 mg mane, 6 mg nocte; or paroxetine 20 mg b.d.). Antidepressant efficacy was assessed by the 21-item Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impression Scale for Severity (CGI-S) at all study visits, and the Clinical Global Impression of Improvement (CGI-I) at each visit after randomization. Sexual function and satisfaction was assessed by visual analogue scale (VAS) items of the Rush Sexual Inventory completed at baseline and days 28 and 56. There were no significant differences between groups in demographic or clinical features at baseline. There was a gradual reduction in severity of depressive symptoms (reboxetine, -14.3; paroxetine, -12.0: observed case analysis), with no significant differences between groups. There were significant differences (p < 0.05), with advantages for reboxetine, at Week 4 and Week 8 on the VAS item assessing ability to become sexually excited, and non-significant trends with advantages for reboxetine, in frequency of sexual thoughts at Week 4 (p = 0.05) and Week 8 (p = 0.08); and in desire to initiate sexual activity at Week 4 (p = 0.09). Exclusion of patients who had ever experienced sexual dysfunction with any medication prior to participation in this study (n = 10) reduced the statistical significance of the findings, although there were still numerical advantages for reboxetine. Sexual function and satisfaction in depressed patients improves during double-blind acute treatment with reboxetine or paroxetine, but this improvement is greater and more rapid with reboxetine.

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Neurol Sci. 2005 Oct;26(4):255-62.
Psychiatric disorders and depression in multiple sclerosis outpatients: impact of disability and interferon beta therapy.
Galeazzi GM, Ferrari S, Giaroli G, Mackinnon A, Merelli E, Motti L, Rigatelli M.
Consultation/Liaison Psychiatry Service, Department of Neuroscience TCR, Section of Psychiatry, University of Modena and Reggio Emilia, Via del Pozzo 71, I-41100, Modena, Italy, galeazzi@unimo.it.

Associations between psychopathology and gender, duration of MS, disability and therapy with beta-interferons were studied in multiple sclerosis (MS) outpatients. A controlled descriptive epidemiological study was carried out in two Italian outpatient MS centres on 50 outpatients with clinically definite relapsing-remitting MS presenting for regular follow-up and 50 healthy controls matched for sex, age and educational level. Subjects were assessed with the Structured Clinical Interview for DSM-IV (SCID I), the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). MS patients reported a higher prevalence of psychiatric disorders (odds ratio 3.17), with 46% (n=23) suffering from major depressive disorder. The risk of suffering from any non-mood psychiatric disorder was also higher in MS patients than in controls (odds ratio 2.67). Risk factors for depression were female sex and severity of disability, but not therapy with interferon beta or longer duration of illness. Disability level, but not therapy with beta-interferons, is a risk factor for depression in MS outpatients. Regular screening for depression in this population is appropriate.

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Ann Med. 2005;37(6):404-12.
The risks and benefits of antidepressant treatment for youth depression.
Bridge JA, Salary CB, Birmaher B, Asare AG, Brent DA.
Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

The U.S. Food and Drug Administration (FDA) has mandated that all antidepressants carry a 'black box' warning label indicating that antidepressants increase the risk of suicidality in youth taking these medications. In the U.K., the Medicine and Healthcare Products Regulatory Agency (MHRA) has determined that the balance of risks and benefits favors only the use of fluoxetine in the treatment of depressive illness in children and adolescents. This article reviews the FDA's analysis linking antidepressant medication use and pediatric suicidality in major depressive disorder, discusses the efficacy of antidepressants in treating depression in children and adolescents, and offers suggestions to aid clinicians, patients, and families in making clinical decisions based on an accurate assessment of the benefits and risks of medication and psychosocial treatments for pediatric depression.

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Int J Neuropsychopharmacol. 2005 Oct 5;:1-6
Phenytoin: an anti-bipolar anticonvulsant?
Bersudsky Y.
Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.

phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. we completed a trial of phenytoin in mania and schizoaffective disorder, manic type. thirty-nine patients entered a 5-wk double-blind controlled trial of haloperidol+phenytoin vs. haloperidol+placebo; 30 patients completed at least 3 wk; 25 completed 5 wk. significantly more improvement was observed in those patients receiving phenytoin. phenytoin has not previously been studied prophylactically in bipolar patients. bipolar patients were studied who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis. patients were stable for a mean of 4 months (range 1-13) before entering the study. phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. thirty observation periods of 6 months each were studied for 23 patients. three patients had relapse on phenytoin and nine had relapse on placebo. there was a significant prophylactic effect of phenytoin in bipolar disorder [cox's f test for comparing survival in two groups: f (6, 18)=3.44, p =0.02]. this study suggests prophylactic effects of add-on phenytoin in bipolar illness. however, the number of patients was small and confirmation is necessary. lamotrigine has recently been reported to have antidepressant effects. in the past, small studies showed antidepressant effects for carbamazepine and valproate. to determine if such effects could be a class property of other voltage-activated sodium channel blockers such as phenytoin, we performed a double-blind controlled trial of phenytoin vs. fluoxetine in unipolar depression. thirty-three depressed patients entered the study, and 28 completed at least 3 weeks and were included in data analyses. weekly hamilton depression scales for 6 wk showed no difference between fluoxetine and phenytoin. clearly pharmaceutical company funding for clinical trials or advertising for phenytoin is minimal and this must be taken into account in evaluating literature on phenytoin vs. other drugs. the present data suggests that effects on affective disorder may be common to many anticonvulsants.

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Am J Psychiatry. 2005 Oct;162(10):1805-19.
Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review
of randomized trials.
Cipriani A, Pretty H, Hawton K, Geddes JR.
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK. john.geddes@psych.ox.ac.uk.

OBJECTIVE: Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder. METHOD: The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966-June 2002), EMBASE (1980-June 2002), CINAHL (1982-March 2001), PsycLIT (1974-June 2002), PSYNDEX (1977-October 1999), and LILACS (1982-March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term "lithium" for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors. RESULTS: In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio=0.26; 95% confidence interval [CI]=0.09-0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio=0.21; 95% CI=0.08-0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio=0.42, 95% CI=0.21-0.87). CONCLUSIONS: Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.

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Clin Psychol Rev. 2005 Sep 29; [Epub ahead of print]
The empirical status of cognitive-behavioral therapy: A review of meta-analyses.
Butler AC, Chapman JE, Forman EM, Beck AT.
University of Pennsylvania and the Beck Institute for Cognitive Therapy and Research, United States.

This review summarizes the current meta-analysis literature on treatment outcomes of CBT for a wide range of psychiatric disorders. A search of the literature resulted in a total of 16 methodologically rigorous meta-analyses. Our review focuses on effect sizes that contrast outcomes for CBT with outcomes for various control groups for each disorder, which provides an overview of the effectiveness of cognitive therapy as quantified by meta-analysis. Large effect sizes were found for CBT for unipolar depression, generalized anxiety disorder, panic disorder with or without agoraphobia, social phobia, posttraumatic stress disorder, and childhood depressive and anxiety disorders. Effect sizes for CBT of marital distress, anger, childhood somatic disorders, and chronic pain were in the moderate range. CBT was somewhat superior to antidepressants in the treatment of adult depression. CBT was equally effective as behavior therapy in the treatment of adult depression and obsessive-compulsive disorder. Large uncontrolled effect sizes were found for bulimia nervosa and schizophrenia. The 16 meta-analyses we reviewed support the efficacy of CBT for many disorders. While limitations of the meta-analytic approach need to be considered in interpreting the results of this review, our findings are consistent with other review methodologies that also provide support for the efficacy CBT.

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Exp Neurol. 2005 Sep 26; [Epub ahead of print]
Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder.
Bajbouj M, Brakemeier EL, Schubert F, Lang UE, Neu P, Schindowski C, Danker-Hopfe H.
Department of Psychiatry, Charite-University Medicine Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.

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Clin Ther. 2005 Aug;27(8):1126-43.
Duloxetine hydrochloride: A new dual-acting medication for the treatment of major depressive disorder.
Hunziker ME, Suehs BT, Bettinger TL, Crismon ML.
College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.

Abstract BACKGROUND:: Duloxetine hydrochloride has recently been approved by the US Food and Drug Administration for the treatment of major depressive disorder (MDD). Duloxetine is a potent inhibitor of serotonin and norepinephrine reuptake, with weak effects on dopamine reuptake. OBJECTIVE:: This article reviews the literature on duloxetine with regard to its pharmacodynamics, pharmacokinetics, clinical efficacy, and tolerability. METHODS:: A comprehensive search of MEDLINE was performed using the terms duloxetine, Cymbalta, and major depressive disorder, with no restriction on year. The Eli Lilly and Company clinical trial registry, and abstracts and posters from recent American Psychiatric Association meetings were also reviewed. RESULTS:: Duloxetine exhibits linear, dose-dependent pharmacokinetics across the approved oral dosage range of 40 to 60 mg/d. No dose adjustment appears to be needed based on age. Duloxetine has shown efficacy in reducing depressive symptoms compared with placebo, and duloxetine recipients have shown significant improvements in global functioning compared with placebo (both, P < 0.05). Response and remission rates have been comparable to or greater than those seen with fluoxetine or paroxetine. Duloxetine is generally well tolerated, with nausea, dry mouth, and fatigue being the most common treatment-emergent adverse effects. Cardiovascular adverse effects do not appear to result in sustained blood pressure elevations, QTc-interval prolongation, or other electrocardiographic changes. CONCLUSIONS:: Based on the available evidence, duloxetine is a well-tolerated and effective treatment for MDD in adults. Randomized head-to-head comparisons against established antidepressants are needed to determine the relative safety and efficacy of duloxetine.

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Nord J Psychiatry. 2005;59(2):127-33.
Adolescent outpatients with depressive disorders: clinical characteristics and treatment received.
Pelkonen M, Marttunen M.
Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland. Mirjami.Pelkonen@ktl.fi

Depressive disorders constitute a common clinical problem. However, research on psychosocial impairment and treatment-related factors among adolescent outpatients with different diagnoses of depression is scarce. This study aimed at investigating consecutively referred outpatient adolescents with depressive syndrome compared with psychiatric controls. We also compared those with major depression (MDD), other depressive disorders (OD), or adjustment disorder with depressed mood (ADDM) in terms of psychosocial impairment and treatment received in a sample of 302 consecutively referred adolescent outpatients. Psychosocial impairment was most severe in MDD. Comorbidity with anxiety disorders characterized those with MDD, whereas antisocial disorders were common among those with OD. Psychosocial treatment was more intensive and psychotropic medication more prevalent in patients with MDD compared with those with OD or ADDM. All the depressed patients receiving psychotropic medication had additional psychosocial treatments. Psychosocial functioning improved in all three groups (MDD, OD, ADDM), whether their treatment involved only psychotherapeutic treatments or additional psychotropic medication. Adolescents with different diagnoses of depression have specific psychosocial impairments that have to be taken into account in developing psychiatric treatments for them.

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CNS Spectr. 2005 Aug;10(8):647-63.
Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects.
Terman M, Terman JS.
Clinical Chronobiology, New York State Psychiatric Institute, New York, NY, USA.

Bright light therapy for seasonal affective disorder (SAD) has been investigated and applied for over 20 years. Physicians and clinicians are increasingly confident that bright light therapy is a potent, specifically active, nonpharmaceutical treatment modality. Indeed, the domain of light treatment is moving beyond SAD, to nonseasonal depression (unipolar and bipolar), seasonal flare-ups of bulimia nervosa, circadian sleep phase disorders, and more. Light therapy is simple to deliver to outpatients and inpatients alike, although the optimum dosing of light and treatment time of day requires individual adjustment. The side-effect profile is favorable in comparison with medications, although the clinician must remain vigilant about emergent hypomania and autonomic hyperactivation, especially during the first few days of treatment. Importantly, light therapy provides a compatible adjunct to antidepressant medication, which can result in accelerated improvement and fewer residual symptoms.

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Psychiatry Res. 2005 Jul 22; [Epub ahead of print]
Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: An exploratory approach.
Zobel A, Joe A, Freymann N, Clusmann H, Schramm J, Reinhardt M, Biersack HJ, Maier W, Broich K.
Department of Psychiatry, University of Bonn, Sigmund-Freud-Strabetae 25, 53105 Bonn, Germany.

Abnormalities in regional cerebral blood flow (rCBF) have been reported to characterize depressive episodes; they are at least partly reversed by antidepressant treatment. Treatment-specific as well as response-related changes in rCBF have been reported. We explored the changes in rCBF induced by vagus nerve stimulation (VNS), a recently proposed antidepressant strategy, by application of single photon emission-computed tomography with (99m)Tc-hexamethyl-propylene amine oxime in otherwise treatment-refractory patients. Both region-of-interest (ROI) and statistical parametric mapping (SPM) analytic approaches were used. Decreases of rCBF in the amygdala, left hippocampus, left subgenual cingulate cortex, left and right ventral anterior cingulum, right thalamus and brain stem were observed; the only increase of rCBF was found by SPM analysis in the middle frontal gyrus. This pattern shares features with changes of rCBF previously associated with the administration of selective serotonin reuptake inhibitors. Similarities to other brain-stimulation strategies in antidepressant treatment were less pronounced.

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Biol Psychiatry. 2005 Jul 22; [Epub ahead of print]
Nutrition and Depression: Implications for Improving Mental Health Among Childbearing-Aged Women.
Bodnar LM, Wisner KL.
Department of Epidemiology, Graduate School of Public Health; Department of Obstetrics, Gynecology, and Reproductive Sciences; School of Medicine; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania.

Adequate nutrition is needed for countless aspects of brain functioning. Poor diet quality, ubiquitous in the United States, may be a modifiable risk factor for depression. The objective was to review and synthesize the current knowledge of the role of nutrition in depression, and address implications for childbearing-aged women. Poor omega-3 fatty acid status increases the risk of depression. Fish oil and folic acid supplements each have been used to treat depression successfully. Folate deficiency reduces the response to antidepressants. Deficiencies of folate, vitamin B12, iron, zinc, and selenium tend to be more common among depressed than nondepressed persons. Dietary antioxidants have not been studied rigorously in relation to depression. Childbearing-aged women are particularly vulnerable to the adverse effects of poor nutrition on mood because pregnancy and lactation are major nutritional stressors to the body. The depletion of nutrient reserves throughout pregnancy and a lack of recovery postpartum may increase a woman's risk of depression. Prospective research studies are needed to clarify the role of nutrition in the pathophysiology of depression among childbearing-aged women. Greater attention to nutritional factors in mental health is warranted given that nutrition interventions can be inexpensive, safe, easy to administer, and generally acceptable to patients.

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Depress Anxiety. 2005 Jul 20; [Epub ahead of print]
Time course of depression-symptom improvement during treatment with duloxetine.
Hirschfeld RM, Mallinckrodt C, Lee TC, Detke MJ.
University of Texas Medical Branch, Galveston, Texas.

The aim of this study was to examine the longitudinal response for overall and individual symptoms during the treatment of major depressive disorder. Data were pooled from two 9-week trials, which compared duloxetine 60-mg QD (n=251) with placebo (n=261) in the treatment of MDD. Changes from baseline in the 17-item Hamilton Depression Rating Scale (HAMD(17)) and in the Visual Analog Scales for pain were analyzed. Compared to placebo-treated patients, duloxetine-treated patients experienced greater improvement (P<.05) in the HAMD(17 )total score at Week 2. The individual symptoms showing the most rapid improvements (Week 1) were depressed mood, guilt, suicidal ideation, work/activities, and psychic anxiety as well as VAS back pain and shoulder pain. At subsequent visits, significant improvements were observed in retardation (Week 2); hypochondriasis (Week 3); general somatic symptoms (Week 5); middle and late insomnia (Week 7); and gastrointestinal (GI) symptoms, genital symptoms (level of sexual interest or ease of sexual arousal), insight, and early insomnia (Week 9). Significant advantages for duloxetine were not achieved at any visit for agitation, somatic anxiety, or weight loss. At Weeks 1 and 2, placebo-treated patients had significantly lower GI symptoms and reported less weight loss compared with duloxetine-treated patients; however, differences were not significant at subsequent visits. Furthermore, duloxetine was superior to placebo on GI symptoms at endpoint compared to placebo-treated patients; duloxetine-treated patients had a significantly higher response rate at Week 2 and a higher remission rate at Week 5. These results may help clinicians establish more accurate expectations regarding treatment with duloxetine. Depression and Anxiety 00:1-8, 2005. (c) 2005 Wiley-Liss, Inc.

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CNS Spectr. 2005 Jun;10(6):suppl 1-11; discuss 12-3; quiz 14-5.
Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data.
Akiskal HS, Fuller MA, Hirschfeld RM, Keck PE Jr, Ketter TA, Weisler RH.
University of California, San Diego, USA.

This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight.) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.

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Essent Psychopharmacol. 2005;6(4):185-92.
The management of fatigue in depressed patients.
Marin H, Menza MA.
Department of Psychiatry, University of Medicine and Dentistry of New Jersey--Robert Wood Johnson Medical School, Piscataway, NewJersey, USA.

Three quarters of patients who respond to treatment with the newer antidepressants still complain of fatigue. Fatigue is one of the most common and disturbing residual symptoms of depression. Increased serotonin activity in certain areas of the brain contributes to fatigue. It can be counteracted by dopaminergic agents which, interestingly, are enhanced by exercise. Specific steps that can be used to address residual fatigue include cognitive interventions based on those used to address somatoform disorders; graded aerobic exercise; dose reduction or discontinuation of fatigue-inducing antidepressants; and the prescription of such medications as dopaminergic antidepressants (bupropion), stimulants, thyroid preparations, and modafinil.

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J Clin Psychiatry. 2005 May;66(SUPPLEMENT 5):40-48.
Atypical Antipsychotics in Bipolar Depression: Potential Mechanisms of Action.
Yatham LN, Goldstein JM, Vieta E, Bowden CL, Grunze H, Post RM, Suppes T, Calabrese JR.
>From the Department of Psychiatry, The University of British Columbia, UBC Hospital, Vancouver, Canada (Dr. Yatham); AstraZeneca, Wilmington, Del. (Dr. Goldstein); Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain (Dr. Vieta); Department of Psychiatry, University of Texas Health Science Center, San Antonio (Dr. Bowden); Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany (Dr. Grunze); the Bipolar Collaborative Network and private practice, Chevy Chase, Md. (Dr. Post); Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Dr. Suppes); and University Hospitals of Cleveland/Case Western Reserve University School of Medicine, Cleveland, Ohio (Dr. Calabrese).

"Conventional" antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), bu-propion, or serotonin-norepinephrine reuptake inhibitors, are not recommended as monotherapy for bipolar depression. Although they are likely to provide effective symptom relief in combination with mood stabilizers, the risk of precipitating a switch to mania often complicates their use even as combination therapy. Recently, 2 psychotropic medications approved for treating acute mania, olanzapine and quetiapine, have also been shown to possess antidepressant activity without destabilizing mood and, as such, are potential mood stabilizers. This article aims to review the mechanism of action of conventional antidepressants and newer agents that are effective in the treatment of bipolar depression. A number of mechanisms have been postulated to play a role in the effective treatment of bipolar depression, including targets as diverse as serotonin (5-HT), norepinephrine, dopamine, gamma-aminobutyric acid (GABA), glutamate, and various second messenger signaling pathways. A review of the data reveals an important point of commonality among the antidepressant treatments, olanzapine, and quetia-pine. Antidepressant treatments, such as norepinephrine reuptake inhibitors, SSRIs, and electrocon-vulsive therapy, induce a reduction of 5-HT(2A) receptors. Both olanzapine and quetiapine not only are antagonists at this receptor but also induce downregulation of 5-HT(2A) receptors. It is possible that the antidepressant efficacy of these agents is mediated by this receptor, while the additional benefit of olanzapine and quetiapine over unimodal antidepressant treatments, in terms of stabilizing mood, may be provided by their concomitant dopamine D(2) antagonism. Further studies should be conducted to examine these hypotheses.

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J Clin Psychiatry. 2005;66 Suppl 5:17-25.
Reevaluating therapies for bipolar depression.
Grunze H.
>From the Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany.

The most commonly employed pharmacotherapies for bipolar depression include antidepressants, lithium, and anticonvulsants, such as lamotrigine, valproate, and carbamazepine. A combination of these agents, usually an antidepressant and a mood stabilizer, is often required to achieve an optimal response. However, some treatment guidelines still caution that antidepressant exposure should be minimized in patients with bipolar depression, due to concern that they may trigger treatment-emergent mania or cycle acceleration. This advice prevails despite data showing that antidepressants are effective in treating bipolar depression and evidence that coadministration of a mood-stabilizing medication, at least with modern antidepressants, such as the selective serotonin reuptake inhibitors, can reduce the risk of treatment-emergent mania to levels comparable with those observed with mood stabilizer monotherapy. Although the antidepressant efficacy of most mood stabilizers has not been satisfactorily proven, first-line therapy with 1 mood stabilizer alone or a combination of 2 mood stabilizers is still recommended by many guidelines. Inappropriate treatment of bipolar depression may leave patients at high risk of suicide and increased chronicity of symptoms; effective therapy should, therefore, be provided as early as possible. The efficacy and safety of antidepressants for bipolar depression both as monotherapy and when combined with a mood stabilizer should be studied in adequately powered trials in order to revise treatment guidelines. Electroconvulsive therapy remains an option for treatment-refractory patients and those intolerant to pharmacologic treatment, as well as patients who are pregnant or at high risk of suicide.

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Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004363.
Antidepressant prevention of postnatal depression.
Howard L, Hoffbrand S, Henshaw C, Boath L, Bradley E.
Box PO29, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK, SE5 8AF.

BACKGROUND: Postnatal depression is a common and important complication of childbearing. Untreated depression can lead to potentially negative effects on the foetus and infant, in addition to serious morbidity for the mother. The use of antidepressants during pregnancy for prevention of postnatal depression is unclear, due to the possibility of adverse effects on the mother and developing foetus, and the difficulty of reliably identifying the women who would go on to develop postnatal depression. OBJECTIVES: To evaluate the effectiveness of different antidepressant drugs in addition to standard clinical care in the prevention of postnatal depression.To compare the effectiveness of different antidepressant drugs and with any other form of intervention for postnatal depression i.e. hormonal, psychological or social support.To assess any adverse effects of antidepressant drugs in either the mother or the foetus/infant. SEARCH STRATEGY: The register of clinical trials maintained and updated by the Cochrane Depression, Anxiety and Neurosis Group and the Cochrane Pregnancy and Childbirth Group. SELECTION CRITERIA: Randomised studies of antidepressants alone or in combination with another treatment, compared with placebo or a psychosocial intervention in non-depressed pregnant women or women who had given birth in the previous six weeks (i.e. women at risk of postnatal depression) DATA COLLECTION AND ANALYSIS: Data were extracted independently from the trial reports by the authors. Missing information was requested from investigators wherever possible. Data were sought to allow an "intention to treat" analysis. MAIN RESULTS: Two trials fulfilled the inclusion criteria for this review. Both looked at women with a past history of postpartum depression. Nortriptyline (n=26) (Wisner 2001) did not show any benefit over placebo (n=25). Sertraline (n=14) Wisner 2004 reduced the recurrence of postnatal depression and the time to recurrence when compared with placebo (n=8). Intention to treat analyses were not carried out in either trial. AUTHORS' CONCLUSIONS: It is not possible to draw any clear conclusions about the effectiveness of antidepressants given immediately postpartum in preventing postnatal depression and, therefore, cannot be recommended for prophylaxis of postnatal depression, due to the lack of clear evidence. Larger trials are needed which also include comparisons of antidepressant drugs with other prophylactic treatments to reflect clinical practice, and examine adverse effects for the foetus and infant, as well as assess womens' attitudes to the use of antidepressants at this time.

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Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004046.
Acupuncture for depression.
Smith C, Hay P.
School of Health Sciences, University of South Australia, City East Campus, GPO Box 2471, Adelaide, South Australia, AUSTRALIA, 5001.

BACKGROUND: There is interest from the community in the use of self help and complementary therapies for depression. This review examined the currently available evidence supporting the use of acupuncture to treat depression. OBJECTIVES: To examine the efficacy and adverse effects of acupuncture for depression. SEARCH STRATEGY: The following databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) MEDLINE (1966 to Sept 2003) EMBASE (1980 to Sept 2003) PSYCINFO (1874 to Sept 2003) the Database of Abstracts of Reviews of Effectiveness (DARE) CISCOM, CINAHL (January 1980 to Sept 2003). The following terms were used: depression, depressive disorder, dysthymic disorder and acupuncture. SELECTION CRITERIA: Inclusion criteria included all published and unpublished randomised controlled trials comparing acupuncture with sham acupuncture, no treatment, pharmacological treatment, other structured psychotherapies (cognitive behavioural therapy, psychotherapy or counselling), or standard care. The following modes of treatment were included: acupuncture, electro acupuncture or laser acupuncture. The subjects included adult men and women with depression defined by clinical state description, or diagnosed by the Diagnostic and Statistical Manual (DSM-IV), Research Diagnostic Criteria (RDC), or the International Classification of Disease (ICD). DATA COLLECTION AND ANALYSIS: Meta analysis was performed using relative risk for dichotomous outcomes and weighted mean differences for continuous outcomes, with 95% confidence intervals. Primary outcomes were reduction in the severity of depression, measured by self rating scales, or by clinician rated scales; and an improvement in depression defined as remission vs no remission. MAIN RESULTS: Seven trials comprising 517 subjects met the inclusion criteria. Five trials (409 subjects) included a comparison between acupuncture and medication. Two other trials compared acupuncture with a wait list control or sham acupuncture. Subjects generally had mild to moderate depression. There was no evidence that medication was better than acupuncture in reducing the severity of depression (WMD 0.53, 95%CI -1.42 to 2.47), or in improving depression, defined as remission versus no remission (RR1.2, 95%CI 0.94 to 1.51). AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the efficacy of acupuncture compared to medication, or to wait list control or sham acupuncture, in the management of depression. Scientific study design was poor and the number of people studied was small.

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Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000448.
St John's Wort for depression.
Linde K, Mulrow C, Berner M, Egger M.
Centre for Complementary Medicine Research, Department of Internal Medicine II, Technische Universitat Munchen, Kaiserstr. 9, Munich, GERMANY, 80801.

BACKGROUND: Extracts of the plant Hypericum perforatum L. (popularly called St. John's wort) have been used in folk medicine for a long time for a range of indications including depressive disorders. OBJECTIVES: To investigate whether extracts of hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of depressive disorders in adults; and whether they have have less adverse effects than standard antidepressant drugs. SEARCH STRATEGY: Trials were searched in computerized databases (Cochrane Collaboration Depression, Anxiety & Neurosis Group Clinical Trials Registers; PubMed); by checking bibliographies of pertinent articles; and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were included if they: (1) were randomized and double-blind; (2) included patients with depressive disorders; (3) compared extracts of St. John's wort with placebo or standard antidepressants; and (4) included clinical outcomes such as scales assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, outcomes and results was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of hypericum with placebo and standard antidepressants was the responder rate ratio (responder rate in treatment group/responder rate in control group). The main outcome measure for adverse effects was the number of patients dropping out for adverse effects. MAIN RESULTS: A total of 37 trials, including 26 comparisons with placebo and 14 comparisons with synthetic standard antidepressants, met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In trials restricted to patients with major depression, the combined response rate ratio (RR) for hypericum extracts compared with placebo from six larger trials was 1.15 (95% confidence interval (CI), 1.02-1.29) and from six smaller trials was 2.06 (95% CI, 1.65 to 2.59). In trials not restricted to patients with major depression, the RR from six larger trials was 1.71 (95% CI, 1.40-2.09) and from five smaller trials was 6.13 (95% CI, 3.63 to 10.38). Trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with selective serotonin reuptake inhibitors (SSRIs) and tri- or tetracyclic antidepressants, respectively, RRs were 0.98 (95% CI, 0.85-1.12; six trials) and 1.03 (95% CI, 0.93-1.14; seven trials). Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (Odds ratio (OR) 0.25; 95% CI, 0.14-0.45); such comparisons were in the same direction, but not statistically significantly different, between hypericum extracts and SSRIs (OR 0.60, 95% CI, 0.31-1.15). AUTHORS' CONCLUSIONS: Current evidence regarding hypericum extracts is inconsistent and confusing. In patients who meet criteria for major depression, several recent placebo-controlled trials suggest that the tested hypericum extracts have minimal beneficial effects while other trials suggest that hypericum and standard antidepressants have similar beneficial effects. As the preparations available on the market might vary considerably in their pharmaceutical quality, the results of this review apply only to the products tested in the included studies.

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Am J Geriatr Psychiatry. 2005 Apr;13(4):305-11.
Maintenance treatment outcomes in older patients with bipolar I disorder.
Sajatovic M, Gyulai L, Calabrese JR, Thompson TR, Wilson BG, White R, Evoniuk G.
correspondence and reprint requests to Martha Sajatovic, Department of Psychiatry, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106. martha.sajatovic@uhhs.com.

OBJECTIVE: The efficacy and tolerability of mood stabilizers in older adults with bipolar disorder remains understudied. Authors retrospectively examined response to lamotrigine, lithium, and placebo in older (>/=age 55) adults with Bipolar I disorder (DSM-IV) who participated in two mixed-age, maintenance studies examining time to intervention for an emerging mood episode (manic/hypomanic/mixed or depressed) and drug tolerability. METHODS: In all, 588 patients received double-blind lamotrigine (LTG, 100 mg-400 mg/day), lithium (Li, 0.8 mEq/L-1.1 mEq/L), or placebo (PBO); data from 98 older adults (LTG: 33, Li: 34, PBO: 31) were examined. Mean modal total daily doses were LTG 240 mg and Li 750 mg. RESULTS: LTG significantly delayed time to intervention for any mood episode and for a depressive episode, compared with placebo. Li significantly delayed time to intervention for mania/hypomania/mixed compared with placebo. Back pain and headache were the most common adverse events during LTG treatment; rash: LTG, 3%; Li, 6%; and PBO, 0; no serious rash was reported. The most common adverse events (>10%) during lithium treatment were dyspraxia, tremor, xerostomia, headache, infection, amnesia, dizziness, diarrhea, nausea, and fatigue. CONCLUSION: Lamotrigine and lithium may be effective and well-tolerated maintenance therapies for older adults with Bipolar I depression.

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Phytother Res. 2005 Apr 25;19(2):148-151 [Epub ahead of print]
Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial.
Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH, Khani M.
Pychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran 13337, Iran.

Depression is a serious disorder in today's society, with estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As a therapeutic plant, saffron is considered excellent for stomach ailments and as an antispasmodic, to help digestion and to increase appetite. It is also used for depression in Persian traditional medicine. Our objective was to assess the efficacy of the stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6-week double-blind, placebo-controlled and randomized trial.Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton rating scale for depression score of at least 18. In this double-blind, placebo-controlled, single-centre and randomized trial, patients were randomly assigned to receive a capsule of saffron 30 mg[sol ]day (BD) (Group 1) or a capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, Crocus sativus produced a significantly better outcome on the Hamilton depression rating scale than the placebo (d.f. = 1, F = 18.89, p < 0.001). There were no significant differences in the two groups in terms of the observed side effects.The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified. Copyright (c) 2005 John Wiley & Sons, Ltd.

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Int J Clin Pract. 2005 Mar;59(3):268-75.
Efficacy of escitalopram in patients with severe depression: a pooled analysis.
Llorca PM, Azorin JM, Despiegel N, Verpillat P.
Centre Medico-Psychologique B, Centre Hospitalier Universitaire, Clermont-Ferrand, France.

Escitalopram is an effective, well-tolerated treatment for major depressive disorder in both primary and specialist settings. This analysis compared the efficacy of escitalopram with citalopram in the treatment of patients with severe depression [defined as a score of > or =30 Montgomery-Asberg Depression Rating Scale (MADRS)]. Data from three clinical trials were used for this pooled analysis. A total of 506 severely depressed patients were included (169 received escitalopram, 171 citalopram and 166 placebo). Mean change from baseline in MADRS total scores (primary efficacy parameter) was significantly higher in the escitalopram-treated group compared with the citalopram-treated group (p = 0.003). There was a significant difference in response between escitalopram and citalopram (56 vs. 41%, respectively, p = 0.007). Results from secondary efficacy parameters (Hamilton rating for depression and Clinical Global Impression of Improvement and Severity scales) were consistent with previous results. The benefits in severe depression of escitalopram vs. citalopram were so demonstrated.

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Ann Gen Psychiatry. 2005 Feb 16;4(1):5.
Review of the use of Topiramate for treatment of psychiatric disorders.
Arnone D.
Department of Psychiatry, Springfield University Hospital, St George's Medical School, London, UK. Danilo.Arnone@swlstg-tr.nhs.uk.

BACKGROUND: Topiramate is a new antiepileptic drug, originally designed as an oral hypoglycaemic subsequently approved as anticonvulsant. It has increasingly been used in the treatment of numerous psychiatric conditions and it has also been associated with weight loss potentially relevant in reversing weight gain induced by psychotropic medications. This article reviews pharmacokinetic and pharmacodynamic profile of topiramate, its biological putative role in treating psychiatric disorders and its relevance in clinical practice. METHODS: A comprehensive search from a range of databases was conducted and papers addressing the topic were selected. RESULTS: Thirty-two published reports met criteria for inclusion, 4 controlled and 28 uncontrolled studies. Five unpublished controlled studies were also identified in the treatment of acute mania. CONCLUSIONS: Topiramate lacks efficacy in the treatment of acute mania. Increasing evidence, based on controlled studies, supports the use of topiramate in binge eating disorders, bulimia nervosa, alcohol dependence and possibly in bipolar disorders in depressive phase. In the treatment of rapid cycling bipolar disorders, as adjunctive treatment in refractory bipolar disorder in adults and children, schizophrenia, posttraumatic stress disorder, unipolar depression, emotionally unstable personality disorder and Gilles de la Tourette's syndrome the evidence is entirely based on open label studies, case reports and case series. Regarding weight loss, findings are encouraging and have potential implications in reversing increased body weight, normalisation of glycemic control and blood pressure. Topiramate was generally well tolerated and serious adverse events were rare.

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Expert Rev Neurother. 2005 Jan;5(1):69-78.
Treatment of bipolar depression: focus on pharmacologic therapies.
Mitchell PB, Malhi GS.
University of New South Wales, School of Psychiatry, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia. phil.mitchell@unsw.edu.au

Recent studies have highlighted significant limitations in our capacity to effectively treat bipolar depression. This article reviews the present status of treatments for this condition, highlighting emerging new pharmacotherapies such as lamotrigine, olanzapine and quetiapine, while also addressing modern psychologic interventions such as cognitive behavioral therapy and psychoeducation. The role of older treatments such as lithium and the antidepressants is also discussed, particularly as a recent meta-analysis has thrown into question current heightened concern over antidepressant-induced mania. The advent of new pharmacologic and psychologic treatments provides optimism for improved outcomes for this highly disabling condition.

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Prostaglandins Leukot Essent Fatty Acids. 2005 Mar;72(3):211-8.
Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression.
Silvers KM, Woolley CC, Hamilton FC, Watts PM, Watson RA.
New Zealand Institute for Crop & Food Research, Private Bag 4704, Christchurch, New Zealand.

Converging evidence suggests that omega-3 polyunsaturated fatty acids have aetiological importance in depression. To determine the effect of adding fish oil to existing therapy in participants who were being treated for depression in a community setting, 77 participants were randomly assigned to receive 8g of either fish or olive oil per day in addition to their existing therapy. Fifty-nine (77%) participants completed 12 weeks of treatment. Dietary, biochemical and lifestyle factors were measured throughout the study. Mood was assessed using the Short Form Hamilton Depression Rating Scale (HDRS-SF) and the Beck Depression Inventory II. Sample size calculations were based on the HDRS-SF. Intention-to-treat and per protocol analyses were carried out using residual maximum likelihood. There was no evidence that fish oil improved mood when compared to the placebo oil, despite an increase in circulating omega-3 polyunsaturated fatty acids. However, mood improved significantly in both groups within the first 2 weeks of the study (P<0.001) and this improvement was sustained throughout. In conclusion, fish oil was no more effective than the control as an add-on therapy for depression in this setting.

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J Clin Psychopharmacol. 2005 Feb;25(1):59-73.
The Use of Selective Serotonin Reuptake Inhibitors During Pregnancy and Breast-feeding: A Review and Clinical Aspects.
Hallberg P, Sjoblom V.
Department of Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden.

ABSTRACT:: Mood and anxiety disorders are common in women during their childbearing years. The prevalence of depression has been reported to be between 10% and 16% during pregnancy. The use of selective serotonin reuptake inhibitors during pregnancy or lactation is, to date, not promoted because of lack of safety documentation. However, the off-label use of these drugs has been common for several years. In the treatment of mood and anxiety disorders during pregnancy, the serotonin reuptake inhibitors are often preferred over tricyclic antidepressants because of their relatively few adverse effects and safety in overdose. This has created concern among women planning pregnancies and pregnant women, as well as among their families and physicians. Several studies and reports of the use of serotonin reuptake inhibitors during both pregnancy and lactation have been published and advanced our knowledge. We here review and discuss those studies which have been published so far on this subject.

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Clin Neurophysiol. 2005 Feb;116(2):386-92.
Effect of electroconvulsive therapy on cortical excitability in patients with major depression: a transcranial magnetic stimulation study.
Chistyakov AV, Kaplan B, Rubichek O, Kreinin I, Koren D, Hafner H, Feinsod M, Klein E.
Laboratory of Clinical Neurosciences, Department of Neurosurgery, Rambam (Maimonides) Medical Center, B. Rappaport Faculty of Medicine, The Technion, Israel Institute of Technology, P.O. Box 9602, Haifa 31096, Israel.

OBJECTIVE: The antidepressant action of electro-convulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) may be related to their ability to modulate cortical excitability. The aim of this study was to investigate changes in cortical excitability following ECT in patients with major depression (MD) and to compare therapeutic efficacy of ECT combined with rTMS to that of ECT alone. METHODS: Twenty-two patients with MD were assigned to receive ECT and right prefrontal 1Hz rTMS (n=12) or ECT with sham rTMS (n=10). ECT was given twice weekly and rTMS was applied on the remaining 4 days, throughout 3 weeks. The resting motor threshold (rMT) and motor evoked potential (MEP)/M-wave area ratio were evaluated before and 6h after the first, third and sixth ECT session. The active motor threshold (aMT), intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF) were measured at baseline and 24h after the last ECT. RESULTS: There were no significant differences in the degree of clinical improvement and measures of cortical excitability in the ECT+active rTMS group as compared to the ECT+sham rTMS group. Marked clinical improvement observed in 19 out of the 22 patients was associated with a significant increase of the MEP/M-wave area ratio, decrease of the aMT and reduction of the ICI in the left hemisphere. CONCLUSIONS: The antidepressant effect of ECT was associated with an enhancement of left hemispheric excitability. rTMS did not add to the beneficial effect of ECT. However, the small sample size and the robust effect of ECT might have obscured a potential therapeutic effect of rTMS. SIGNIFICANCE: Measures of cortical excitability may provide insight to our understanding of the mechanism of action of ECT and might be useful for the assessment of treatment response.

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Biol Psychiatry. 2005 Jan 15;57(2):162-6.
Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: A double-blind placebo-controlled study.
Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C, Myczkowski ML, Moreno RA, Marcolin MA.
Institute of Psychiatry, University of Sao Paulo, Faculty of Medicine, Sao Paulo-SP, Brazil.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. Three recent meta analyses strongly suggest its benefits in the treatment of depression. The present study investigates whether repetitive TMS (rTMS) accelerates the onset of action and increases the therapeutic effects of amitriptyline. METHODS: Forty-six outpatients meeting DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial. All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of motor threshold and 1250 pulses per session). Sham stimulation followed the same schedule, however, using a sham coil. The efficacy variables were the Hamilton Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression (CGI). Tolerability was assessed by clinical examination and a safety screening of TMS side effects. RESULTS: Repetitive TMS had a significantly faster response to amitriptyline. There was a significant decrease in HAM-D/17 scores, already after the first week of treatment (p < .001 compared with baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study (p < .001 at fourth week). CONCLUSIONS: Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline.

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CNS Drugs. 2005;19(1):43-54.
Efficacy and tolerability of reboxetine in depressive patients treated in routine clinical practice.
Messer T, Schmauss M, Lambert-Baumann J.
Clinic for Psychiatry and Psychotherapy, Regional Hospital Augsburg, Augsburg, Germany.

OBJECTIVES: Reboxetine, a potent and selective noradrenaline reuptake inhibitor, has been approved for treatment of major depression. The aim of this study was to investigate the efficacy and tolerability of reboxetine in depressive outpatients undergoing treatment in routine clinical practice. STUDY DESIGN AND METHODS: This post-marketing surveillance study was conducted to evaluate the therapeutic efficacy and tolerability of standard therapeutic doses of reboxetine in patients with depressive symptoms, particularly when administered in routine clinical practice. The 1835 patients (mean 54 years of age) evaluated showed demographic characteristics representative of the general depressive population. The majority of patients received the recommended dose of reboxetine 8 mg/day.RESULTS: Measures of efficacy showed improvement in depressive symptoms with reboxetine therapy over the mean observational period of 9.6 weeks. Response to therapy, defined as Hamilton depression scale 21-item version score reduction of >/=50%, was reported in 83% of patients. The effects of reboxetine were rated by physicians as 'good' or 'very good' in 86% of patients at the last visit. The tolerability of reboxetine was rated by physicians as 'good' or 'very good' in 92% of patients at all evaluations. No adverse events that were possibly related to reboxetine therapy occurred in >1% of patients.CONCLUSION: The results of this study suggest that reboxetine is safe and well tolerated and may improve symptoms in depressive patients treated in routine clinical practice.

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Bull Acad Natl Med. 2004;188(6):999-1007; discussion 1007-10.
[Depression and aging]
[Article in French]
Loo H, Gallarda T, Fabre I, Olie JP.
Service Hospitalo-Universitaire de Sante Mentale et de Therapeutique, CH Sainte-Anne, 1 rue Cabanis, 75674 Paris 14.

Depression is one of the most common health disorders in elderly people. It is still often considered as a natural consequence of aging, arising in reaction to a medical disease, cognitive or functional decline, or a loss of social fabric. Many studies have highlighted the low rates of diagnosis and treatment of depression, especially in the primary care setting. Major depression in old age is characterized by the same core symptoms as in other periods of life. However, aging may accentuate some symptoms and alleviate others. Somatic concern, marked anxiety, poor subjective memory, psychotic ideation, and recurrent thoughts of death can mask sadness and anhedonia. Organic factors and adverse life events are often intricately linked with the pathogenesis of depressive states in the elderly. The role of cerebrovascular lesions has also been established, particularly in late-onset depressive disorders. The management of depressive disorders in older people, as in younger adults, involves pharmacological and psychological treatments. Electroconvulsive therapy can be beneficial in some cases. Transcranial magnetic stimulation is being evaluated in this setting.

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J Child Adolesc Psychopharmacol. 2004 Fall;14(3):412-7.
Safety of subchronic treatment with fluoxetine for major depressive disorder in children and adolescents.
Nilsson M, Joliat MJ, Miner CM, Brown EB, Heiligenstein JH.
Eli Lilly and Company, Indianapolis, IN 46285, USA.

OBJECTIVE: The aim of this study was to assess the safety of subchronic fluoxetine treatment for major depressive disorder (MDD) in children and adolescents. METHODS: Patients received up to 19 weeks of treatment with fluoxetine, 10 mg-60 mg daily. Safety was evaluated through the reporting of concomitant medications, vital signs, routine laboratory testing, electrocardiograms (ECGs), and adverse event data. RESULTS: Ninety-six patients, aged 9-17 years, completed 19 weeks of treatment with fluoxetine (n = 49) or placebo (n = 47). There were statistically significant differences between the fluoxetine and placebo groups in mean change from baseline for alkaline phosphatase and total cholesterol levels (p < 0.001, and p < 0.014, respectively), but there were no statistically significant differences between the incidence of abnormal laboratory values for these 2 analytes. Fluoxetine-treated patients gained statistically significantly less height (fluoxetine: 1.0 cm +/- 2.4; placebo: 2.1 cm +/- 2.6; p = 0.004) and weight (fluoxetine: 1.2 kg +/- 2.7; placebo: 2.3 kg +/- 2.6; p = 0.008) than placebo-treated patients during the 19 weeks of treatment. There was no difference in the rate of reported suicide-related events between fluoxetine and placebo. CONCLUSION: Fluoxetine was found to be safe and well tolerated in this study of children and adolescents with MDD. Clarification and determination of the clinical significance of the growth-rate reduction seen during fluoxetine treatment requires further investigation. During treatment with fluoxetine, the growth of child and adolescent patients should be monitored.

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Cochrane Database Syst Rev. 2004 Oct 18(4):CD001134.
Psychosocial and psychological interventions for preventing postpartum depression.
Dennis CL, Creedy D.
Faculty of Nursing, University of Toronto, 50 St George Street, Toronto, Ontario, CANADA, M5S 3H4.

BACKGROUND: The cause of postpartum depression remains unclear, with extensive research suggesting a multi-factorial aetiology. However, epidemiological studies and meta-analyses of predictive studies have consistently demonstrated the importance of psychosocial and psychological variables. While interventions based on these variables may be effective treatment strategies, theoretically they may also be used in pregnancy and the early postpartum period to prevent postpartum depression. OBJECTIVES: Primary: to assess the effect of diverse psychosocial and psychological interventions compared with usual antepartum, intrapartum, or postpartum care to reduce the risk of developing postpartum depression. Secondary: to examine (1) the effectiveness of specific types of psychosocial and psychological interventions, (2) the effectiveness of individual versus group-based interventions, (3) the effects of intervention onset and duration, and (4) whether interventions are more effective in women selected with specific risk factors. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (January 27 2004), the Cochrane Depression, Anxiety and Neurosis Group trials register (October 2003), the Cochrane Central Register of Controlled Trials (October 2003), MEDLINE (1966 to 2004), EMBASE (1980 to 2004) and CINAHL (1982 to 2004). We scanned secondary references and contacted experts in the field. SELECTION CRITERIA: All published and unpublished randomised controlled trials of acceptable quality comparing a psychosocial or psychological intervention with usual antenatal, intrapartum, or postpartum care. DATA COLLECTION AND ANALYSIS: Both reviewers participated in the evaluation of methodological quality and data extraction. Additional information was sought from several trial researchers. Results are presented using relative risk for categorical data and weighted mean difference for continuous data. MAIN RESULTS: Fifteen trials, involving over 7600 women, were included. Overall, women who received a psychosocial intervention were equally likely to develop postpartum depression as those receiving standard care (relative risk (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.02). One promising intervention appears to be the provision of intensive postpartum support provided by public health nurses or midwives (RR 0.68, 95% CI 0.55 to 0.84). Identifying mothers 'at-risk' assisted the prevention of postpartum depression (RR 0.67, 95% CI 0.51 to 0.89). Interventions with only a postnatal component appeared to be more beneficial (RR 0.76, 95% CI 0.58 to 0.98) than interventions that also incorporated an antenatal component. While individually-based interventions may be more effective (RR 0.76, 95% CI 0.59 to 1.00) than those that are group-based, women who received multiple-contact intervention were just as likely to experience postpartum depression as those who received a single-contact intervention. REVIEWERS' CONCLUSIONS: Overall psychosocial interventions do not reduce the numbers of women who develop postpartum depression. However, a promising intervention is the provision of intensive, professionally-based postpartum support.

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J Clin Psychiatry. 2004 Oct;65(10):1323-1328.
A 3-Month, Follow-Up, Randomized, Placebo-Controlled Study of Repetitive Transcranial Magnetic Stimulation in Depression.
Koerselman F, Laman DM, van Duijn H, van Duijn MA, Willems MA.
From the Departments of Psychiatry (Drs. Koerselman and Willems) and Neurophysiology (Drs. Laman and H. van Duijn), St. Lucas Andreas Hospital, Amsterdam; the Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht (Dr. Koerselman); and the Department of Statistics and Measurement Theory, University of Groningen, Groningen (Dr. M. A. J. van Duijn), the Netherlands.

BACKGROUND/OBJECTIVE: There is evidence for an antidepressant effect of repetitive transcranial magnetic stimulation (rTMS), but little is known about posttreatment course. Therefore, we conducted a placebo-controlled, double-blind study in depressed patients in order to investigate the effect of rTMS on depression over 12 weeks after completion of the 2-week stimulation period. METHOD: 55 patients with a moderate or severe DSM-IV major depressive episode were randomly assigned to rTMS or sham treatment. rTMS was given daily for 10 days over the left dorsolateral prefrontal cortex with the following treatment parameters: 20 Hz, 20 trains of 2 seconds, 30 seconds between trains, and 80% motor threshold. The effect of rTMS on depression was rated repeatedly with the 17-item Hamilton Rating Scale for Depression (HAM-D) during the 2-week period of stimulation and the 12-week follow-up period conducted from 1997 to 2001. RESULTS: We found a modest, clinically nonrelevant decrease in HAM-D scores in both rTMS and sham patients over 2 weeks of treatment. However, over the subsequent 12-week follow-up, the rTMS group continued to improve significantly compared with the placebo group. CONCLUSION: Decrease of depressive symptoms may continue after the cessation of rTMS stimulation.

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J Affect Disord. 2004 Oct 15;82(2):303-307.
Safety of Hypericum extract in mildly to moderately depressed outpatients; A review based on data from three randomized, placebo-controlled trials.
Trautmann-Sponsel RD, Dienel A.
Psychosomatische Klinik GmbH and Co., Schutzenstrasse 16, 86949 Windach, Germany.

Rationale: Hypericum extracts have been regarded as antidepressant drugs wihtout specific side effects by patients, medical professionals and researchers alike. Recently there has been discussion about potential interactions between St. John's wort and other drugs. Objectives: To investigate the tolerability of Hypericum extract by comparing adverse event rates observed during clinical trials with the herbal drug to those observed under placebo and synthetic antidepressants. Methods: A data review was performed based on the original data of three double-blind, randomised multicenter trials, during which 594 out-patients suffering from mild to moderate depression according to DSM-IV criteria received 3 x 300 mg/day Hypericum extract (WS(R) 5570, WS(R) 5572, WS(R) 5573) or placebo over a double-blind treatment period of 6 weeks. For the polled data from the three trials, the risk ratios and risk differences versus placebo for single and grouped adverse events were determined along with their 95% confidence intervals. The data were inspected for relevant differences between Hypericum extract and placebo and were compared to trials involving the adminstration of several synthetic antidepressants. Results: For the polled data of the three trials, the percentage of patients with any adverse events under Hypericum extract exposition was comparable to placebo. The drug was also found to be devoid of effects of sedation, anticholinergic reactions, gastrointestinal disturbances and sexual dysfunction often found in patients treated with tricyclic antidepressants or selective serotonin reuptake inhibitors. Conclusion: The analysis did not reveal any specific effects of Hypericum extract.

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Zh Nevrol Psikhiatr Im S S Korsakova. 2004;104(9):39-42.
[Use of cypramil in the treatment of depression in patients with gastrointestinal cancer]
[Article in Russian]
[No authors listed]

Depressive state in cancer patients is known to meet the criteria of mild depressive episode (F33.0) according to ICD-10. In the earlier stages of the disease and after successful treatment, depressive symptoms are usually combined with anxiety and obsessive fear, moderate appearances of ideator and motor inhibition, with permanent presence of asthenic symptoms. Once the disease is getting severer and the treatment is less successful, asthenia acquires hyposthenic features, with symptoms of apathy and dysphoria being attached. Cypramil was shown to be an effective medication in the treatment of depression in patients with malignant tumors of gastric-intestinal tract. The most efficient was the treatment conducted on the earlier stages of the cancer process and in cases of successful surgery and chemotherapy, in combination of depression with anxiety, anxious hypochondria, asthenia. Antidepressants must be used together with psychotherapy.

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Zh Nevrol Psikhiatr Im S S Korsakova. 2004;104(9):32-8.
[Preventive efficacy of tianeptine in recurrent depression with frequent exacerbations]
[Article in Russian]
[No authors listed]

The results of the studies of 4 Russian research centers are summarized. Tianeptine (coaxil) was used in the treatment of 55 patients with ICD-10 diagnosis of recurrent depressive disorder (F32.1), 50 patients have completely finished the treatment. Tianeptine was assigned in dosage of 12.5 mg 3 times daily (patients over 65 years old received 25.0 mg daily) during 12 months. The drug was shown to have a high preventive efficacy for the disorder. Sixty-one percent of patients were full-responders. Taken together with partial responders (13%), an improvement was observed in 74% patients. The drug demonstrated a well tolerability with a rare and mild expression of side-effects.

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Wien Med Wochenschr. 2004 Aug;154(15-16):378-82.
[Inpatient treatment of women with depressive disorders due to stress--does inclusion of the partner in treatment influence outcome? A randomized, controlled, prospective study]
[Article in German]
Nickel M, Nickel C, Tritt K, Lahmann C, Leiberich P, Loew T, Rother W.
Inntalklinik, Fachklinik fur Psychosomatik, Simbach/Inn, Deutschland. m.nickel@inntalklinik.de

BACKGROUND: The incorporation of couple therapy into the treatment concepts of inpatient psychotherapy has been intensified in recent years. However, no controlled studies on its efficacy have as yet been undertaken. The aim of this study was to examine this question in the case of women with depressive symptomology related to overstress. METHODS: In a prospective, randomized and controlled study, the monitored results of 31 female inpatients (15 for whom the partner was incorporated into the therapy and 16 without additional partner therapy) were compared with each other (response rate 91.2 %). The period of observation amounted to six weeks. The Beck Depression Inventory (BDI) and the Questionnaire on Changes in Experience and Behavior) (VEV) were employed as instruments of assessment. RESULTS: VEV assessment after six weeks resulted in a significant difference between patients who received regular sessions in couple therapy in an inpatient treatment setting and those who were treated without inclusion of the partner (p < 0.01). The Beck Depression Inventory likewise yielded a statistically significant difference between the results for both groups (p < 0.05). CONCLUSIONS: There are indications that female patients with depressive symptomology related to overstress, who are treated in an inpatient setting with additional, consistent couple therapy, achieve significantly better treatment results than those who are treated without the inclusion of their partners.

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Kardiologiia. 2004;44(3):20-4.
[Clinical efficacy of tianeptine in patients with ischemic heart disease and comorbid depression]
[Article in Russian]
[No authors listed]

Ischemic heart disease patients (20 men, 20 women, age 36-72 years) with class II-III effort angina and depression (Beck Depression Inventory -- BDI -- score > or = 19) were randomized to standard therapy were treatment of stable ischemic heart disease (control group) or standard therapy plus tianeptine 37.5 mg/day. After 6 weeks 52% decrease of BDI score occurred in tianeptine treated patients (from 24.9+/-1.2 to 11.9+/-1.5, p<0.001). This was associated with decrease of number and severity of cardialgias, better blood pressure control in patients with hypertension, lengthening of exercise time during exercise test (by 3.3+/-0.9 min, p<0.05), and increase of overall index of quality of life (by 2.6+/-0.9 points, p<0.01). No dynamics of these parameters occurred in control group.

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Kardiologiia. 2004;44(10):49-53.
[Clinical efficacy of citalopram in patients with hypertension and concomitant depression.]
[Article in Russian]
Pogosova GV, Gudkova OA, Iufereva IuM, Tikhomirova EA.
Research Center for Preventive Medicine; Petroverigsky per. 10, 101953 Moscow, Russia.

Patients (n=28) with mild to moderate hypertension and depression were given enalapril (20 mg/day). If target blood pressure was not achieved in 10 days hydrochlorothiazide (12.5 mg/day) was added. These patients were randomized into 2 groups in one of which antihypertensive therapy was supplemented with citalopram (20 mg/day) for 6 weeks. Psychological status was assessed by Beck Depression Inventory (BDI) and Spielberger State-Trait Anxiety Inventory (STAI). Total BDI score in citalopram group decreased 51% (-12.2+/-1.5; p<0.001). Complete reduction of symptoms of depression (BDI score <19) occurred in 86% of patients. There was no significant lowering of BDI score in control group. STAI score among citalopram treated patients with concomitant anxiety (STAI score >50) decreased from initial 62.9+/-2.1 to 46.3+/-3.1 by week 6 (p<0.001). Only minor changes of STAI score took place in control group. According to data of 24-hour monitoring lowering of systolic blood pressure time indexes was somewhat more pronounced in citalopram group than in control group (24 hour -49.8 and -34.4%, diurnal -56.6 and -42%, nocturnal -37.9 and -23%, respectively).

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J Am Acad Child Adolesc Psychiatry. 2004 Aug;43(8):1003-1010.
School-Based Prevention of Depressive Symptoms in Adolescents: A 6-Month Follow-up.
POssel P, Horn AB, Groen G, Hautzinger M.
Department of Clinical and Physiological Psychology, University of Tubingen (P.P., A.B.H., M.H.) and University of Bremen (G.G.), Germany.

OBJECTIVE:: Depressive disorders in adolescents are a widespread problem with extensive psychosocial consequences. The authors designed a school-based program to prevent the increase in depressive symptoms. The authors expect the program to reduce dysfunctional automatic thoughts and improve social skills and thus prevent the increase in depressive symptoms. METHOD:: The design includes a training group and a nontreatment control group with pre- and post-measurement and 3- and 6-month follow-up. The authors followed up 324 eighth graders in both groups. School classes were randomly assigned to one of the two groups. The prevention program, LISA-T, is based on cognitive-behavioral therapy concepts and targets of cognitive and social aspects. It comprises 10 meetings of 1.5 hours in a regular school setting. RESULTS:: Increases in depressive symptoms in nondepressed adolescents in the training group were prevented over a 6-month period. Furthermore, adolescents with subsyndromal depression in the training group reported fewer symptoms, whereas depressive symptoms within the control group did not change. However, the groups did not differ with regard to social skills, frequency of negative automatic thoughts, and depressive symptoms before the prevention program. CONCLUSIONS:: LISA-T is an effective school-based prevention program for eighth graders with minimal to mild depressive symptoms, but further research is needed.

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J Am Acad Child Adolesc Psychiatry. 2004 Aug;43(8):930-959.
Cognitive-Behavioral Psychotherapy for Anxiety and Depressive Disorders in Children and Adolescents: An Evidence-Based Medicine Review.
Compton SN, March JS, Brent D, Albano AM 5th, Weersing R, Curry J.

OBJECTIVE:: To review the literature on the cognitive-behavioral treatment of children and adolescents with anxiety and depressive disorders within the conceptual framework of evidence-based medicine. METHOD:: The psychiatric and psychological literature was systematically searched for controlled trials applying cognitive-behavioral treatment to pediatric anxiety and depressive disorders. RESULTS:: For both anxiety and depression, substantial evidence supports the efficacy of problem-specific cognitive-behavioral interventions. Comparisons with wait-list, inactive control, and active control conditions suggest medium to large effects for symptom reduction in primary outcome domains. CONCLUSIONS:: From an evidence-based perspective, cognitive-behavioral therapy is currently the treatment of choice for anxiety and depressive disorders in children and adolescents. Future research in this area will need to focus on comparing cognitive-behavioral psychotherapy with other treatments, component analyses, and the application of exportable protocol-driven treatments to divergent settings and patient populations.

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Cochrane Database Syst Rev. 2004;3:CD003437.
Interventions for treating depression after stroke.
Hackett M, Anderson C, House A.
Clinical Trials Research Unit, University of Auckland, Private Bag 92019, Auckland, NEW ZEALAND.

BACKGROUND: Depressive and anxiety disorders following stroke are often undiagnosed or inadequately treated. This may reflect difficulties with the diagnosis of abnormal mood among older people with stroke-related disability, but may also reflect uncertainty about the effectiveness of such therapies in this setting. OBJECTIVES: To determine whether pharmacological, psychological, or electroconvulsive treatment (ECT) of depression in patients with stroke can improve outcome. SEARCH STRATEGY: The Cochrane Stroke Group Trials Register (last searched June 2003). The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to September 2002), CINAHL (1982 to September 2002), PsychINFO (1967 to September 2002), Applied Science and Technology Plus (1986 to September 2002), Arts and Humanities Index (1991 to September 2002), Biological Abstracts (1969 to September 2002), General Science Plus (1994 to September 2002), Science Citation Index (1992 to September 2002), Social Sciences Citation Index (1991 to September 2002), and Sociofile (1974 to September 2002). Reference lists from relevant articles and textbooks were searched, and authors of known studies and pharmaceutical companies who manufacture psychotropic medications were contacted. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different types of pharmaceutical agents with placebo, or various forms of psychotherapy with standard care (or attention control), in patients with recent, clinically diagnosed, acute stroke, where treatment was explicitly intended of treat depression. DATA COLLECTION AND ANALYSIS: Primary analyses focussed on the prevalence of diagnosable depressive disorder at the end of treatment. Secondary outcomes included depression or mood scores on standard scales, disability or physical function, death, recurrent stroke, and adverse effects. We did not pool the data for summary scores. We performed meta-analysis for only some binary endpoints and data on adverse events. MAIN RESULTS: Nine trials, with 780 participants, were included in the review. Data were available for seven trials of pharmaceutical agents, and two trials of psychotherapy. There were no trials of ECT. The analyses were complicated by the lack of standardised diagnostic and outcome criteria, and differing analytic methods. There was no strong evidence of benefit of either pharmacotherapy or psychotherapy in terms of a complete remission of depression following stroke. There was evidence of a reduction (improvement) in scores on depression rating scales, and an increase in the proportion of participants with anxiety at the end of follow up. REVIEWERS' CONCLUSIONS: This review found no evidence to support the routine use of pharmacotherapeutic or psychotherapeutic treatment for depression after stroke. More research is required before recommendations can be made about the most appropriate management of depression following stroke.

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Int J Nurs Pract. 2004 Aug;10(4):177-94.
The effectiveness of a pram-walking exercise programme in reducing depressive symptomatology for postnatal women.
Armstrong K, Edwards H.
Researcher, Centre for Nursing Research, Queensland University of Technology, Kelvin Grove, Queensland, Australia.

The purpose of the research project was to examine the effects of exercise, social support and depression on postnatal women who reported experiencing postnatal depression. A 12-week randomized, controlled trial was conducted investigating the effects of an exercise intervention group (a pram-walking programme for mothers and their babies ) compared to a social support group (non-structured sessions, similar to a playgroup). Participants in both groups had given birth in the past 12 months. Pretest data of physical fitness and structured questionnaires were compared to post-test effects. The primary outcomes were to reduce the depressive symptomatology and improve fitness levels of participants in the pram-walking group. Secondary outcomes were to improve the social support levels of the participants in both groups and explore women's views about the programmes. It was hypothesized that the pram-walking group participants would improve their feelings of depression and fitness levels compared to the social support group, but that both groups would improve their perceived levels of social support. The results showed that mothers in the pram-walking intervention group improved their fitness levels and reduced their level of depressive symptomatology significantly more than the social support group. There were no significant changes to social support levels for both groups. Therefore, a direct association between improvement in fitness was related to improvement in depression for the pram-walking group. However, it is also suggested that other factors in combination with improvements in fitness influenced improvements in depression levels. It is recommended that pram-walking programmes for mothers with postnatal depression be implemented as pilot research into existing available services.

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J Psychiatr Ment Health Nurs. 2004 Aug;11(4):476-83.
Exercise: a neglected intervention in mental health care?
Callaghan P.
Reader in Mental Health, Head of Department of Mental Health and Learning Disability, City University, London, UK.

CALLAGHAN P. (2004) Journal of Psychiatric and Mental Health Nursing11, 476-483 Exercise: a neglected intervention in mental health care?This paper reports the results of a literature review examining the effects of exercise on mental health and well-being. Throughout history many societies, ancient and modern, have used exercise as a means of preventing disease, and promoting health and well-being. There is evidence that exercise is beneficial for mental health; it reduces anxiety, depression, and negative mood, and improves self-esteem and cognitive functioning. Exercise is also associated with improvements in the quality of life of those living with Schizophrenia. However, exercise is seldom recognized by mainstream mental health services as an effective intervention in the care and treatment of mental health problems. There is evidence to suggest that exercise may be a neglected intervention in mental health care.

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J Natl Cancer Inst Monogr. 2004;(32):150-7.
Symptom management in the elderly cancer patient: fatigue, pain, and depression.
Rao A, Cohen HJ.
Center for Aging, Duke University Medical Center, Box 3003, Durham, NC 27710. harvey.cohen@duke.edu

Patients who are >/=65 years of age are the fastest growing segment of the U.S. population. These patients with already existing physiologic decline and comorbidities, when diagnosed with cancer, provide considerable challenges in management issues. Along with therapy for the tumor the practicing oncologist must also keep in mind the various symptoms, like fatigue, pain, and depression, that may occur due to the tumor itself or due to therapy. The prevalence of fatigue is greater than 50-70% in advanced cancer. The tools to measure fatigue are all subjective in nature and no one tool has been tested in the elderly cancer patient. Treatment of fatigue in the elderly may involve education, antidepressants, treatment of anemia, exercise, and use of psychostimulants. Pain is present is 80% of elderly patients with advanced cancer. Pain should be assessed in a systematic way and it has been shown that the Visual Descriptor Scale is the tool most preferred by the elderly. Several guidelines for management of pain exist and options include acetaminophen, nonsteroidal anti-inflammatory drugs, opioids, adjuvant analgesics, and education of patients and caregivers. Depression is also a prevalent symptom arising from a variety of causes. There are many validated tools to measure depression in the elderly like the Geriatric Depression Scale. Treatment includes use of education, selective serotonin reuptake inhibitors, psychotherapy, and electroconvulsive therapy. There exists an interplay of many of these symptoms and quite often they can occur simultaneously in the elderly cancer patient. Future research is needed to expand our base of knowledge on the occurrence and management of each of these symptoms and to better understand how aging systems interact with these phenomena to produce unique situations in older adults.

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J Natl Cancer Inst Monogr. 2004;(32):105-11.
Treatment of depression in cancer.
Fisch M.
Palliative Care and Rehabilitation, Box 008, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston TX 77030-4009. mfisch@mdanderson.org

Depression occurs in about 15% of the general population and is at least two to three times more common in patients with cancer. Depression is often difficult to diagnose in these patients because of the complexity and constraints of cancer care, patient and family reluctance to acknowledge distress, and the presence of multiple other symptoms. Both antidepressants and psychotherapy are effective in treating depression in patients with cancer, much like in patients with other significant medical problems. Precise assessments of the benefits of treating depression in these patients are important in weighing them against the costs and potential adverse effects. Such estimates are limited by a paucity of randomized, placebo-controlled trials and methodological problems in the existing studies that reflect some of the clinical difficulties in case-finding, treatment, and follow-up of patients with cancer. The existing body of research about depression in cancer patients is extremely limited in terms of the number of studies published and the number of total patients reported over the last 30 years. Moreover, these limited data may not generalize well because of high rates of patient dropout and the very limited enrollment of children, adolescents, older adults, and minority groups. There is an emerging trend toward simplifying the assessment of depression in outpatient cancer care settings and studying depression therapies in cohorts of patients with cancer other than those with fully characterized depressive disorders.

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J Gen Intern Med. 2004 Aug;19(8):813-8.
The outcome of physical symptoms with treatment of depression.
Greco T, Eckert G, Kroenke K.

OBJECTIVE: This study examined the prevalence, impact on health-related quality of life (HRQoL), and outcome of physical symptoms in depressed patients during 9 months of antidepressant therapy. DESIGN: Open-label, randomized, intention-to-treat trial with enrollment occurring April through November 1999. SETTING: Thirty-seven primary care clinics within a research network. PATIENTS: Five hundred seventy-three depressed patients started on one of three selective serotonin reuptake inhibitors (SSRIs) by their primary care physician and who completed a baseline interview. INTERVENTIONS: Patients were randomized to receive fluoxetine, paroxetine, or sertraline. MEASUREMENTS AND MAIN RESULTS: Outcomes assessed included physical symptoms, depression, and multiple domains of HRQoL. Prevalence of physical symptoms was determined at baseline and after 1, 3, 6, and 9 months of treatment. Stepwise linear regression models were used to determine the independent effects of physical symptoms and depression on HRQoL domains. Of the 14 physical symptoms assessed, 13 were present in at least a third to half of the patients at baseline. Each symptom showed the greatest improvement during the initial month of treatment. In contrast, depression continued to show gradual improvement over a 9-month period. Physical symptoms had a predominant effect on pain (explaining 17% to 18% of the variance), physical functioning (13%), and overall health perceptions (13% to 15%). Depression had the greatest impact on mental (26% to 45%), social (14% to 32%), and work functioning (9% to 32%). CONCLUSIONS: Physical symptoms are prevalent in depressed patients and initially improve in the first month of SSRI treatment. Unlike depression, however, improvement in physical symptoms typically plateaus with minimal resolution in subsequent months. J GEN INTERN MED 2004;19:813-818.

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J Clin Psychiatry. 2004;65 Suppl 10:11-5.
Evaluation and management of breakthrough depressive episodes.
Keck PE.
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Clinicians are faced with a diagnostic challenge when a bipolar patient reports breakthrough depressive symptomatology. Breakthrough depressive symptoms during treatment for a bipolar depressive episode may be a manifestation of recurrent bipolar depression or the emergence of a mixed episode. Treatment of recurrent bipolar depression and mixed episodes differs considerably, and antidepressant therapy during a mixed episode can worsen the episode and initiate or exacerbate rapid cycling. Therefore, accurate diagnosis and appropriate treatment are imperative to achieving a positive outcome. Research indicates that optimizing the current mood stabilizer therapy or adding another mood stabilizer may be the best treatment options for patients with a history of rapid cycling-in patients without a history of rapid cycling, adding an antidepressant to a mood stabilizer may be less risky and therefore a reasonable choice. Combination therapy with a mood stabilizer and an atypical antipsychotic may also be effective in managing bipolar depressive episodes.

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Issues Ment Health Nurs. 2004 Jul-Aug;25(5):473-86.
Electroconvulsive therapy: present and future.
Gomez GE.
The University of Texas--Houston, Health Science Center, School of Nursing, Houston, Texas 77030, USA. gerda.e.gomez@uth.tmc.edu

Electroconvulsive therapy (ECT) has been used to treat patients for 60 years. It is a humane and effective treatment. It is now firmly established as an important and effective method of treating certain severe forms of depression. Still, very little is known about its mode of action. Research in the refinement of administration has reduced undesirable side effects. There are almost no absolute contraindications to its administration. Nurses are involved directly with patients before, during, and after treatment.

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JAMA. 2004 Jul 21;292(3):338-43.
Antidepressants and the risk of suicidal behaviors.
Jick H, Kaye JA, Jick SS.
Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Mass 02421, USA. hjick@bu.edu

CONTEXT: The relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has received considerable public attention recently. The use of such drugs among teenagers has been of particular concern. OBJECTIVE: To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin. DESIGN AND SETTING: Matched case-control study of patients treated in UK general practices using the UK General Practice Research Database for 1993-1999. PARTICIPANTS: The base population included 159,810 users of the 4 antidepressant drugs. Participants could have used only 1 of these antidepressants and had to have received at least 1 prescription for the study antidepressant within 90 days before their index date (the date of suicidal behavior or ideation for cases and the same date for matched controls). MAIN OUTCOME MEASURES: Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior. RESULTS: After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin. The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date. Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and suicidal behavior since its relation to suicidal behavior was not materially different among users of the 4 study drugs. Similarly for fatal suicide, the RR among patients who were first prescribed an antidepressant within 1 to 9 days before their index date was 38.0 (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant 90 days or more before their index date. There were no significant associations between the use of a particular study antidepressant and the risk of suicide. CONCLUSIONS: The risk of suicidal behavior after starting antidepressant treatment is similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin. The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days. A possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression. Based on limited information, we also conclude that there is no substantial difference in effect of the 4 drugs on people aged 10 to 19 years.

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Int J Group Psychother. 2004 Jul;54(3):295-319.
Group therapy for depressed elderly women.
Husaini BA, Cummings S, Kilbourne B, Roback H, Sherkat D, Levine R, Cain VA.
Center for Health Research at Tennessee State University, Nashville 37209, USA. bahusaini@earthlink.net

We describe and evaluate a group therapy program targeting depression among elderly residents (N=303) of subsidized high-rise apartments in Nashville, TN. This eclectic program was comprised of 12 sessions (a total of 24 hours) that included modules on exercise and preventive health behaviors, cognitive and re-motivation therapy, reminiscence and grief therapy, and social skills development. Our multivariate regression analyses of pre-post measures using the Geriatric Depression Scale (GDS) showed that the effects of the group therapy varied by race, age, and level of initial depression among the participants. The program was effective in reducing depression, but only among Caucasian women who reported at least moderate depression prior to the program, and it yielded greater benefits for women between 55 and 75 years of age.

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Arch Gen Psychiatry. 2004 Jul;61(7):714-9.
Combined pharmacotherapy and psychological treatment for depression: a systematic review.
Pampallona S, Bollini P, Tibaldi G, Kupelnick B, Munizza C.
forMed, Evolene, Switzerland.

BACKGROUND: Adherence to antidepressant medication use is a problem in clinical practice. Some authors have posited that combined psychological treatment facilitates adherence to pharmacotherapy. OBJECTIVES: To study the relationship between adherence to use of and efficacy of antidepressant drugs plus psychological treatment vs drug treatment alone in depressive disorders. DATA SOURCES: MEDLINE, Current Contents, PsychInfo, Cochrane Library, and reference lists were searched, from January 1980 to November 2002. STUDY SELECTION: Randomized clinical trials comparing antidepressant treatment alone with antidepressant treatment in combination with a psychological intervention in depressive disorders were considered. The decision to include studies in the meta-analysis was performed by 2 reviewers. DATA EXTRACTION: Three independent reviewers extracted the data, using a precoded form. Methodological quality of the studies was evaluated in terms of allocation concealment and independence of evaluators. DATA SYNTHESIS: Sixteen trials met the inclusion criteria, with 932 patients randomized to pharmacotherapy alone and 910 to combined treatment. Overall, patients receiving combined treatment improved significantly compared with those receiving drug treatment alone (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.38-2.52), but dropouts and nonresponders did not differ in distribution between the 2 treatment modalities (OR, 0.86; 95% CI, 0.60-1.24). Studies longer than 12 weeks showed a significant advantage of combined treatment over drug treatment alone (OR, 2.21; 95% CI, 1.22-4.03), with a significant reduction in dropouts compared with nonresponders (OR, 0.59; 95% CI, 0.39-0.88). These estimates were not affected by study quality. CONCLUSIONS: Psychological treatment combined with antidepressant therapy is associated with a higher improvement rate than drug treatment alone. In longer therapies, the addition of psychotherapy helps to keep patients in treatment. Further studies are needed to investigate whether the improvement in response attributable to the combination of drug treatment and psychotherapy can be achieved by a combination of pharmacotherapy and a compliance-enhancing intervention.

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J Psychopharmacol. 2004 Jun;18(2):251-6.
Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials.
Taylor MJ, Carney SM, Goodwin GM, Geddes JR.
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.

The objective of this review was to determine the effectiveness, adverse effects and acceptability of folate in the treatment of depression. Electronic databases (Cochrane Controlled Trials Register and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register) and reference lists were searched, and authors, experts and pharmaceutical companies contacted to identify randomized controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, for patients with a diagnosis of depressive disorder. Three randomized trials (247 participants) were included. Two studies assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale (HDRS) scores on average by a further 2.65 points [95% confidence interval (CI) 0.38-4.93]. Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at 10 weeks (relative risk 0.47, 95% CI 0.24-0.92). The remaining study found no statistically significant difference when folate alone was compared with trazodone. The identified trials did not find evidence of any problems with the acceptability or safety of folate. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.

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JAMA. 2004 Apr 7;291(13):1569-77.
Community-integrated home-based depression treatment in older adults: a randomized controlled trial.
Ciechanowski P, Wagner E, Schmaling K, Schwartz S, Williams B, Diehr P, Kulzer J, Gray S, Collier C, LoGerfo J.
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98195-6560, USA. pavelcie@u.washington.edu

CONTEXT: Older adults with social isolation, medical comorbidity, and physical impairment are more likely to be depressed but may be less able to seek appropriate care for depression compared with older adults without these characteristics. OBJECTIVE: To determine the effectiveness of a home-based program of detecting and managing minor depression or dysthymia among older adults. DESIGN AND SETTING: Randomized controlled trial with recruitment through community senior service agencies in metropolitan Seattle, Wash, from January 2000 to May 2003. PATIENTS: One hundred thirty-eight patients aged 60 years or older with minor depression (51.4%) or dysthymia (48.6%). Patients had a mean of 4.6 (SD, 2.1) chronic medical conditions; 42% of the sample belonged to a racial/ethnic minority, 72% lived alone, 58% had an annual income of less than 10 000 dollars, and 69% received a form of home assistance. INTERVENTIONS: Patients were randomly assigned to the Program to Encourage Active, Rewarding Lives for Seniors (PEARLS) intervention (n = 72) or usual care (n = 66). The PEARLS intervention consisted of problem-solving treatment, social and physical activation, and potential recommendations to patients' physicians regarding antidepressant medications. MAIN OUTCOME MEASURES: Assessments of depression and quality of life at 12 months compared with baseline. RESULTS: At 12 months, compared with the usual care group, patients receiving the PEARLS intervention were more likely to have at least a 50% reduction in depressive symptoms (43% vs 15%; odds ratio [OR], 5.21; 95% confidence interval [CI], 2.01-13.49), to achieve complete remission from depression (36% vs 12%; OR, 4.96; 95% CI, 1.79-13.72), and to have greater health-related quality-of-life improvements in functional well-being (P =.001) and emotional well-being (P =.048). CONCLUSIONS: The PEARLS program, a community-integrated, home-based treatment for depression, significantly reduced depressive symptoms and improved health status in chronically medically ill older adults with minor depression and dysthymia.

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Rev Prat. 2004 Apr 15;54(7):734-8.
[Treatment of depression in the elderly]
[Article in French]
Robert PH.
Centre Memoire de ressources & de recherche, CHU, Universite de Nice-Sophia Antipolis--Pavilion M, hopital Pasteur, 06002 Nice. PHILIPPE.ROBERT15@wanadoo.fr

Depression is the most common mental health problem of later life. There is effective treatments for depression in primary care. Recommendation based on current evidence are: in primary care treatment there is no evidence that one class of antidepressant is anymore effective than others; although newer antidepressants are not more effective than older ones, they are better tolerated in healthy older people and in patients with medical co-morbidity and are safer especially in overdose. Lower dose antidepressant treatment is not recommended for older depressed patients.

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Rev Prat. 2004 Apr 15;54(7):725-33.
[Depressive disorders in old age]
[Article in French]
Clement JP.
Pole de psychiatrie du sujet age, centre hospitalier Esquirol, 87025 Limoges Cedex. jean-pierre.clement@chello.fr

Depression is the most usual mental disorder in the elderly, but underdiagnosed and undertreated. Its prevalence is variable and depends on type and severity of episode. Nevertheless, even subsyndromic depression needs to be correctly treated. Depressive symptomatology observed in the elderly is often similar to adult presentation, but it can be masked and difficult to recognise. The different clinical features are described with underlining their particularities. Secondary depressions are also evoked with individualisation of "vascular" depression and its etiopathogenic hypotheses in relationship with observations given by cerebral neuro-imagery. Risk factors of depression in old age are known, but recent studies have reviewed some of them, particularly by distinguishing late onset depression and early onset depression. According to therapeutic response and prognosis, it appears necessary to better discriminate them. Risk of dementia after depression seems to be related with type of depressive episode and with the treatment efficacy. Finally, the problem of detection of depression in old age is discussed with a suggestion to use assessment instruments as the mini-GDS in all medical practices, to optimise diagnosis and management.

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Clin Neuropharmacol. 2004 Mar-Apr;27(2):90-2.
Antidepressants in the treatment of psychosis with comorbid depression in Parkinson disease.
Voon V, Lang AE.
University of Toronto, Toronto Western Hospital University Health Network, Ontario, Canada. valerie.voon@uhn.on.ca

Psychotic symptoms are commonly associated with Parkinson disease and can be a source of significant morbidity. Depression has been reported as a comorbidity in patients with psychosis. We describe a patient with Parkinson disease with psychotic symptoms and comorbid depression whose treatment refractory delusions and hallucinations improved markedly only after antidepressant monotherapy was initiated. The phenomenology of the delusions was atypical for those found in Parkinson or in depression. Psychotic symptoms refractory or only partially responsive to conventional treatment should prompt a search for potential underlying psychiatric comorbidities. Given case reports of exacerbation of psychotic symptoms with antidepressants, we emphasize careful identification and active follow up of the comorbid depressive disorders in PD patients with psychosis. Potential mechanisms implicated in the response of psychosis to antidepressants are discussed.

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Biol Psychiatry. 2004 Feb 15;55(4):398-405.
Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.
Jorge RE, Robinson RG, Tateno A, Narushima K, Acion L, Moser D, Arndt S, Chemerinski E.
Department of Psychiatry, Carver College of Medicine, University of Iowa, Psychiatry Research/2-202 MEB, Iowa City, IA 52242-1000, USA.

BACKGROUND: Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. METHODS: We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. RESULTS: When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.

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J Gerontol A Biol Sci Med Sci. 2004 Jan;59(1):75-8.
Effects of testosterone on behavior, depression, and cognitive function in older men
with mild cognitive loss.
Kenny AM, Fabregas G, Song C, Biskup B, Bellantonio S.
Center on Aging, MC-5215, University of Connecticut Health Center, Farmington, CT 06030-5215, USA. kenny@nso1.uchc.edu

BACKGROUND: The role of sex hormones in the prevention of cognitive decline is uncertain. Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function. But, there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment. METHODS: In this pilot study, 11 men (mean age 80 +/- 5 years, range 73-87 years) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive intramuscular testosterone (200 mg every 3 weeks) or placebo for 12 weeks. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex hormone binding globulin, estradiol, and estrone), Behave AD Questionnaire, Katz Activities of Daily Living, Geriatric Depression Scale, Digit Span, Clock Face Drawing, Clock Face Perception, Verbal Fluency, Trail-Making B, and International Prostate Symptom Score at baseline, 4 weeks, and 10 weeks. RESULTS: All men completed the study. Total and bioavailable testosterone, estrone, and estradiol levels increased in men receiving testosterone, but no changes were detected in men receiving placebo. No significant changes were found in behavior following testosterone supplementation, nor was there evidence of change in depression or activities of daily living. No discernable changes were found in any of the cognitive tests. Symptoms of prostate hyperplasia remained unchanged in the testosterone (6.6 + 5.8 to 5.2 + 3.6; p =.39) and placebo (8.8 + 6.4 to 6.4 + 3.8; p =.15) groups, and prostate-specific antigen levels did not change significantly. CONCLUSION: No significant changes in behavior, function, depression, or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment. This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors.

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Psychol Bull. 2004 Jan;130(1):3-18.
A meta-analysis of massage therapy research.
Moyer CA, Rounds J, Hannum JW.
Department of Educational Psychology, University of Illinois at Urbana-Champaign, Champaign, IL 61820-6990, USA.

Massage therapy (MT) is an ancient form of treatment that is now gaining popularity as part of the complementary and alternative medical therapy movement. A meta-analysis was conducted of studies that used random assignment to test the effectiveness of MT. Mean effect sizes were calculated from 37 studies for 9 dependent variables. Single applications of MT reduced state anxiety, blood pressure, and heart rate but not negative mood, immediate assessment of pain, and cortisol level. Multiple applications reduced delayed assessment of pain. Reductions of trait anxiety and depression were MT's largest effects, with a course of treatment providing benefits similar in magnitude to those of psychotherapy. No moderators were statistically significant, though continued testing is needed. The limitations of a medical model of MT are discussed, and it is proposed that new MT theories and research use a psychotherapy perspective.

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Eur Neuropsychopharmacol. 2003 Mar;13(2):57-66.
The pharmacology of putative early-onset antidepressant strategies.
Blier P.
Department of Psychiatry, McKnight Brain Institute, University of Florida, Room L4-100, PO Box 100256, Gainesville, FL 32610-0383, USA. blier@psych.med.ufl.edu

Depression is a serious and burdensome illness. Although selective serotonin reuptake inhibitors (SSRIs) have improved safety and tolerability of antidepressant treatment efficacy, the delay in the onset of action have not been improved. There is evidence to suggest that the delay in onset of therapeutic activity is a function of the drugs, rather than the disease. This suggests that research into the biological characteristics of depression and its treatments may yield faster-acting antidepressants. Emerging evidence from clinical studies with mirtazapine, venlafaxine and SSRI augmentation with pindolol suggests that these treatments may relieve antidepressant symptoms more rapidly than SSRIs. The putative mechanism of action of faster-acting antidepressant strategies presented here purports that conventional antidepressants acutely increase the availability of serotonin (5-hydroxytryptamine, 5-HT) or noradrenaline (NA), preferentially at their cell body level, which triggers negative feedback mechanisms. After continued stimulation, these feedback mechanisms become desensitised and the enhanced 5-HT availability is able to enhance 5-HT and/or NA neurotransmission. Putative fast-onset antidepressants, on the other hand, may uncouple such feedback control mechanisms and enhance 5-HT and/or NA neurotransmission more rapidly. Further studies are required to characterise in detail the interactions between NA and 5-HT systems and to definitively establish the early onset of candidate antidepressants such as mirtazapine, venlafaxine and pindolol augmentation.

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Am J Med. 2003 Jan;114(1):15-9.
Early antidepressant therapy for elderly patients.
Freund KM, Moskowitz MA, Lin TH, McKinlay JB.
Section of General Internal Medicine, Evans Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118-2334, USA. karen.freund@bmc.org

PURPOSE: We studied factors affecting the management of depression in older patients, especially the use of early antidepressant therapy. METHODS: We recruited 128 primary care physicians to view one version of a 5-minute videotape of an elderly patient with somatic symptoms that were suggestive of depression, and to complete an interview that assessed decision making. Using an experimental factorial design, 16 versions of the videotape were produced, holding constant the clinical features of the case, while varying the patient's age, race, sex, and socioeconomic status. Dependent variables were the physicians' probability assessment of depression and the recommendation of antidepressant medication after the first visit. RESULTS: Depression was considered a possible diagnosis by 121 physicians (95%) and the most likely diagnosis by 69 (54%). Sixteen physicians (13%) recommended antidepressant therapy after the first visit, and they were less likely than other physicians to order initial laboratory tests to assess the possibility of other conditions. Recommendations for antidepressant therapy was not associated with patient age, sex, race, or socioeconomic status, or with physician sex, race, or experience. Family physicians were more likely than internists to recommend an antidepressant (19% [12/64] vs. 6% [4/64], P = 0.04). CONCLUSION: Based on a 5-minute vignette, physicians were likely to recognize depression, independent of patient characteristics. Those recommending early antidepressant therapy were more likely to be in family medicine and less likely to investigate other diagnoses initially.

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J Consult Clin Psychol. 2003 Apr;71(2):386-93.
The prevalence and impact of large sudden improvements during adolescent therapy for depression: a comparison across cognitive-behavioral, family, and supportive therapy.
Gaynor ST, Weersing VR, Kolko DJ, Birmaher B, Heo J, Brent DA.
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. scott.gaynor@wmich.edu

This study assessed the treatment specificity and impact on outcome of large, abrupt symptomatic improvements occurring prior to and during cognitive-behavioral, family, and supportive therapy. Eighty-seven depressed adolescents receiving at least 8 therapy sessions were included. Abrupt large decreases in depressive symptoms were identified by changes in weekly Beck Depression Inventory scores. Overall, 28% experienced a pretreatment gain and 39% a sudden within-treatment gain. Both types of gains were associated with superior outcome on self-report and interviewer ratings of depression. Among those participants failing to experience a pretreatment or sudden within-treatment gain, cognitive-behavioral therapy produced the superior outcomes. These findings suggest pretreatment and sudden within-treatment gains are important therapeutic events worthy of further investigation.

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J Obstet Gynecol Neonatal Nurs. 2003 Mar-Apr;32(2):239-48.
Depression in adolescence.
Hauenstein EJ.
University of Virginia, School of Nursing, Charlottesville 22908-0782, USA. ejh7m@Virginia.edu

Major depressive disorder is a common problem for adolescents. It has a wide array of symptoms affecting somatic, cognitive, affective, and social processes. Academic failure, poor peer relationships, behavioral problems, conflict with parents and other authority figures, and substance abuse are some of the consequences of major depressive disorder in this age group. Effective treatments include nontricyclic antidepressants and coping skills training. The nurse is key to depression detection and suicide prevention, especially in primary care settings. Through psychoeducation, nurses can promote recovery from depression by encouraging a healthy lifestyle, enhancing social skills, and assisting the adolescent to identify and use sources of social support. These measures can prevent premature death and promote long-term well-being of the adolescent.

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Psychol Assess. 2003 Mar;15(1):29-40.
Interpersonal problems, personality pathology, and social adjustment after cognitive therapy
for depression.
Vittengl JR, Clark LA, Jarrett RB.
Division of Social Science, Truman State University, 100 East Normal Street, Kirksville, Missouri 63501-4221, USA. vittengl@truman.edu

The authors examined the level and structure of the Inventory of Interpersonal Problems-Circumplex version (IIP-C; L. M. Horowitz, L. E. Alden, J. S. Wiggins, & A. L. Pincus, 2000) before and after 20 sessions of acute-phase cognitive therapy for depression (N = 118), as well as associations with the Schedule for Nonadaptive and Adaptive Personality (L. A. Clark, 1993b) and the Social Adjustment Scale--Self-Report version (M. M. Weissman & S. Bothwell, 1976). Interpersonal problems had a 3-factor structure (Interpersonal Distress, Love, and Dominance), with the latter 2 factors approximating a circumplex, both before and after therapy. Interpersonal Distress decreased and social adjustment increased with therapy, but the Love and Dominance dimensions were relatively stable, similar to personality constructs. Social adjustment related negatively to Interpersonal Distress but not to Love or Dominance. Personality pathology related broadly to Interpersonal Distress and discriminantly to Love and Dominance. These findings support the reliability and validity of the IIP-C and are discussed in the context of personality theory and measurement.

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Seishin Shinkeigaku Zasshi. 2002;104(10):810-8.
[Pharmacogenomics and future antidepressant research]
[Article in Japanese]
Yamada M.
Department of Psychiatry, Showa University, Karasuyama Hospital.

Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Pharmacogenomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool we have previously identified more than 300 cDNA fragments as antidepressant-related genes. Some of these candidate genes may encode common functional molecules induced by chronic antidepressant treatment. Defining the roles of these molecules in drug-induced neural plasticity is likely to transform the course of research on the biological basis of antidepressants. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Novel biological approaches beyond the "monoamine hypothesis" are expected to evoke paradigm shifts in the future of antidepressant research.

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CNS Drug Rev. 2003 Spring;9(1):57-96.
The pharmacology of CP-154,526, a non-peptide antagonist of the CRH1 receptor: a review.
Seymour PA, Schmidt AW, Schulz DW.
CNS Discovery, Pfizer Global Research and Development, Groton Laboratories, Pfizer Inc., CT 06340, USA. patricia_a_seymour@groton.pfizer.com

Since CRH has been shown to mediate stress-induced physiological and behavioral changes, it has been hypothesized that CRH receptor antagonists may have therapeutic potential in disorders that involve excessive CRH activity. CP-154,526 and its close analog antalarmin are potent, brain-penetrable, selective nonpeptide CRH1 receptor antagonists that were discovered in an effort to develop compounds with efficacy in CNS disorders precipitated by stress. Since its discovery many investigators have used CP-154,526 as a tool to study the pharmacology of CRH and its receptors and to evaluate its therapeutic potential in a variety of CNS and peripheral disorders. Systemically-administered CP-154,526 has been demonstrated to antagonize CRH- and stress-induced neuroendocrine, neurochemical, electrophysiological, and behavioral effects. These findings support the hypothesis that CRH1 receptor antagonists may have therapeutic utility in a number of neuropsychiatric disorders. CP-154,526, as well as other CRH1 receptor antagonists that have since been discovered, have also shown activity in several preclinical models of anxiety, depression, and substance abuse, while having little effect on locomotor activity and motor function. Although these effects are on occasion inconsistent among different laboratories, clinical evaluation of CRH1 antagonists appears justified on the basis of these and clinical data implicating the involvement of CRH in several CNS disorders. The effects of CRH1 antagonists on cognition, neurodegeneration, inflammation, and the gastrointestinal system have not been as extensively characterized and additional studies will be necessary to evaluate their therapeutic potential in these areas.

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J Pak Med Assoc. 2002 Nov;52(11):518-25.
Efficacy and tolerability of Paroxetine 20 mg daily in the treatment of depression and depression associated anxiety.
Chaudhry HR, Qureshi Z, Tareen IA, Yazdani I.
Department of Psychiatry, Fatima Jinnah Medical College and Sir Ganga Ram Hospital, Lahore.

OBJECTIVE: To assess the efficacy and tolerability of paroxetine 20mg daily, for the treatment of depression and depression associated with anxiety. METHOD: An open, non-comparative study undertaken at three centers in three cities of Pakistan. A total of 112 in- or out-patients, presenting with a major depressive episode were included in the study. Depression was diagnosed according to DSM IV criteria and a Hamilton Rating Scale for Depression (HAMD-D) score of >18 on the first 17 items of the HAM-D-21. After a placebo washout period of 7 days, patients were given a 20-mg fixed dose of paroxetine daily in the morning for a period of 6 weeks. After baseline, regular assessments were made at 1, 2, 4 and 6 weeks. Efficacy measures included the HAMD-D, the Clinical Anxiety Scale, The Clinical Global Impression Severity of Illness Scale (CGI-S), and the Clinical Global Impression Improvement Scale (CGI-I). Tolerability was assessed by any adverse event. The primary therapeutic outcome measures were patients who achieved a 50% or greater reduction in HAMD-D score at the end of the treatment or achieved a reduction in final HAMD-D score of < or = 10 points. The final scores of 1 or 2 for CGI-S and CGI-I were considered as full clinical response. RESULTS: Of 112 cases evaluated, 57 were males and 55 females whose ages ranged from 18 to 65 years. There was a clear and statistically significant efficacy of paroxetine on all the major outcome variables. A total of 88% patients achieved a reduction in the final HAMD-D score at the end of treatment. The total HAM-D score reduced to 10 or less in 73% patients at 6 weeks and by this week 76% and 92% patients achieved a score of 1 or 2 for CGI-S and CGI-I, respectively. The mean Clinical Anxiety Scale score reduced from 12.6 at the baseline to 4.4 at the end of treatment. Safety data was evaluated in all 112 patients and paroxetine was well tolerated. Adverse events were experienced by 10% of patients of whom 4% were dropped from the study. Nausea was the commonest adverse event reported. CONCLUSION: The study shows that paroxetine is an effective, well-tolerated, and safe drug for the treatment of depression.

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Cochrane Database Syst Rev. 2002;(4):CD003944.
The efficacy of antidepressants in the treatment of depression in dementia.
Bains J, Birks JS, Dening TR.
Department of Psychiatry, Manly Hospital (North Sydney Area Health), East Wing, Manly Hospital, Sydney, NSW, Australia, 2095. jbains@med.usyd.edu.au

BACKGROUND & OBJECTIVES: The use of antidepressants for patients with dementia accompanied by depressive symptoms is widespread, but their clinical efficacy is uncertain. This uncertainty is due to the difficulties of interpreting the results of clinical trials. Many of the individual trials of antidepressants have been too small to provide precise estimates of the moderate benefits that might realistically be expected. Combining the information from all appropriate trials may provide a better estimate of the likely effects of treatment. This review aims to determine whether antidepressants are clinically effective and acceptable for the treatment of patients diagnosed as having depression and also diagnosed as having dementia. SEARCH STRATEGY: The CDCIG Specialized Register which includes records from all major medical databases and many trial databases was searched on 21 January 2001. The (long) list of search terms can be found in the main body of the review. Medical information departments of pharmaceutical companies were asked to search their databases for any relevant clinical trials. Where necessary authors of trials were approached with requests for additional information. SELECTION CRITERIA: All relevant unconfounded, double-blind, randomized trials comparing any antidepressant drug (as defined by the British National Formulary) with placebo, for patients diagnosed as having dementia and diagnosed as having a depression, according to established criteria. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two of the reviewers and any differences settled by agreement. MAIN RESULTS: There were six included studies with a total 1077 subjects, of whom 739 met inclusion criteria. Of these, four studies (including a total of 234 subjects) reported results in sufficient detail to enter into meta-analyses. One study's results were limited to adverse results data, therefore the meta-analysis concerning efficacy was limited to three studies (Lyketsos 2000, Petracca 1996, Reifler 1989), with a total of 107 subjects. Of these three studies, two (Petracca 1996, Reifler 1989) investigated the properties of tricyclic antidepressants, drugs not commonly used in this population, and only one study investigated the properties of the more commonly used selective serotonin reuptake inhibitors (Lyketsos 2000). One of these studies (Lyketsos 2000) produced two significant differences in favour of treatment, the Cornell Scale for Depression in Dementia at 6-9 weeks (WMD -7.1, 95% CI -13.05, -1.15) and the psychiatrists' global rating (Peto OR (95% Fixed) 8.17 (1.58, 42.09)). However, the Cornell Scale for Depression in Dementia was not used in any of the other studies and no statistical differences were found with the other measures used in the meta-analysis. The meta-analysis of the number of patients suffering at least one adverse event at 6-9 weeks, using the Peto-odds ratio, showed a significant difference in favour of placebo. There were no other significant results. REVIEWER'S CONCLUSIONS: Available evidence offers weak support to the contention that antidepressants are an effective treatment for patients with depression and dementia. However, only three studies are included in the meta-analysis relating to efficacy, and sample sizes are small. Moreover, only one of the studies included in the analysis of efficacy data investigated the properties of the more commonly used selective serotonin reuptake inhibitors and no studies investigated the properties of newer classes of antidepressants (e.g. selective noradrenergic reuptake inhibitors). This review draws attention to the paucity of research and evidence in this area. It is not that antidepressants are necessarily ineffective but there is not much evidence to support their efficacy either. Given that they may produce serious side-effects clinicians should prescribe with due caution.

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Mt Sinai J Med. 2003 Jan;70(1):38-44.
Overview: depression in the elderly.
Serby M, Yu M.
Department of Psychiatry, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003, USA.

Depression in the elderly population is a major public health problem. It has a high prevalence, is frequently co-morbid with medical illnesses, impacts negatively on quality of life, increases the number of visits to different medical services, and carries a high risk of suicide, especially in men. Imaging studies have increased our understanding of the biological mechanisms of depression in the elderly. Depression is sometimes difficult to diagnose in the elderly. It should be differentiated from apathetic states ( negative syndrome ), and its treatment requires knowledge of specific physiological changes that occur in this age group. Geriatric depression is more somatic and less ideational than depression in other age groups. Acute treatments with various antidepressant medications, augmentation strategies, electroconvulsive treatments, and psychotherapy must be coupled with maintenance strategies to prevent recurrences, which are common.

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Arch Women Ment Health. 2002 Oct;5(2):39-47.
Critical appraisal of effects of estrogen replacement therapy on symptoms of depressed mood.
Stoppe G, Doren M.
Department of Psychiatry and Psychotherapy, Georg-August-University, Gottingen, Germany. gstoppe@gwdg.de

That estrogen plays a role in the regulation of mood has been postulated since extracts of animal ovarian tissue were administered to oophorectomized women at the end of the last century to alleviate psychological symptoms thought to be related to the removal of the ovaries. The occurrence of depressive symptoms in the perimenopause is associated with a variety of factors. A previous history of either depression and/or premenstrual syndrome as well as cognitive factors explain most of the variance. There are no consistent findings of a correlation between any serum hormone level and severity or presence of mood symptoms. Neurobiological studies show, with regard to an antidepressant effect, promising effects of estradiol on serotonergic, noradrenergic, cholinergic, dopaminergic and GABAergic functions. Progestogens seem to oppose some of these effects. The role of adrenergic hormones and DHEA(S) is less clear. Most clinical trials showed a modest effect on symptoms of depression. However, the predominantly poor methodological quality does not allow generalisation and recommendations. A "tonic" effect on well-being in non- or mild depressed women should not be regarded as true antidepressant effect. Results yielded in studies of surgically menopausal women may not be applicable to women with natural menopause. There is a great potential for exploring various types, doses, and routes of administration of both antidepressants and sex hormones. With regard to the domino theory, future studies should also focus on the mediation of treatment effects through alleviation of vasomotor symptoms or sleep quality.

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Psychiatr Pol. 2002 Sep-Oct;36(5):793-804.
[Surgical treatment of mental disorders]
[Article in Polish]
Harat M, Rudas M.
Kliniki Neurochirurgii 10 WSK w Bydgoszczy.

AIM: The surgical treatment of mental disorders--the authors present the neuroanatomical base of stereotactic operations on the limbic system in patients with the mental disorders. METHOD: Four main procedures are discussed: anterior cinguotomy, anterior capsulotomy, subcaudate tractotomy, limbic leucotomy. RESULTS: On the ground of available literature the authors present the results of these operations which are performed with the use of stereotactic equipment guided by MRI and CT. In this article the indications for different surgical procedures are presented and refer mainly to depression, obsessive-compulsive disorder and anxiety. The authors present the principles of qualification and the exclusion criteria of the patients in the countries in which these kinds of operations are performed.

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Psychiatry Res. 2002 Dec 30;116(3):151-61.
An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding.
Mischoulon D, Dougherty DD, Bottonari KA, Gresham RL, Sonawalla SB, Fischman AJ, Fava M.
Department of Psychiatry, Massachusetts General Hospital, 15 Parkman Street, WAC 812, Boston, MA 02114, USA. dmischoulon@partners.org

Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [18F]-setoperone for 5-HT2 binding potential (BP) and [11C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [18F]-setoperone and with [11C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as >or=50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP.

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J Clin Epidemiol. 2002 Oct;55(10):1049-53.
Concomitant prescribing of benzodiazepines during antidepressant therapy in the elderly.
van Dijk KN, de Vries CS, ter Huurne K, van den Berg PB, Brouwers JR, de Jong-van den Berg LT.
Department of Social Pharmacy, Pharmacoepidemiology and Pharmacotherapy, Groningen University Institute for Drug Exploration (GUIDE), Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

A follow-up study was performed in two ambulatory cohorts aged > or =65 to investigate whether the prevalence and incidence of anxiolytic/hypnotic benzodiazepine drug prescribing is comparable between users of serotonin reuptake inhibitors (SSRIs) and users of tricyclic antidepressants (TCAs). The prevalence and incidence of benzodiazepines during antidepressant therapy was estimated among users of TCAs and SSRIs. Coprescribing of benzodiazepines occurred in 53% of the TCA users and 57% of the SSRI users (prevalence RR 1.1; CI(95) 0.9-1.2). The average duration of benzodiazepine drug use was >65 days per 100 days of antidepressant use. During SSRI therapy, significantly more people started benzodiazepine drug therapy than during TCA therapy (incidence rate ratio (RR) 1.7; CI(95) 1.2-2.4). Analyses repeated 5 years later yielded similar results (overall incidence RR(MH) 1.6; CI(95) 1.3-2.0). These data indicate that SSRI use is associated with a significantly higher chance of starting benzodiazepines compared with TCA use.

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Zhonghua Yi Xue Za Zhi (Taipei). 2002 Aug;65(8):349-60.
New methods of minimally invasive brain modulation as therapies in psychiatry: TMS, MST,
VNS and DBS.
George MS.
Center for Advanced Imaging Research, Brain Stimulation Laboratory, Institute of Psychiatry, Medical University of South Carolina, Charleston, South Carolina 29425, USA. georgem@musc.edu

Over the past 20 years, new methods have been developed that have allowed scientists to visualize the human brain in action. Initially positron emission tomography (PET) and now functional magnetic resonance imaging (fMRI) are causing a paradigm shift in psychiatry and the neurosciences. Psychiatry is abandoning the pharmacological model of 'brain as soup', used for much of the past 20 years. Instead, there is new realization that both normal and abnormal behavior arise from chemical processes that occur within parallel distributed networks in specific brain regions. Many of these pathological circuits are becoming well characterized, in disorders ranging from Parkinson's disease, to obsessive-compulsive disorder, to depression. Most recently, there has been an explosion of new techniques that allow for direct stimulation of these brain circuits, without the need for open craniotomy and neurosurgical ablation. The techniques include transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). This review will describe these new tools, and overview their current and future potential for research and clinical neuropsychiatric use. The psychiatry of the future will be better grounded in a firm understanding of neuroanatomy and neurophysiology (as well as pharmacology). These brain stimulation tools, or their next iterations, will play an ever-larger role in clinical neuropsychiatric practice.

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Am J Clin Nutr. 2002 Nov;76(5):1158S-61S.
Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence.
Mischoulon D, Fava M.
Harvard Medical School, Depression Clinical and Research Program, Massachusetts General Hospital, Boston 02114, USA. dmischoulon@partners.org

Major depression remains difficult to treat, despite the wide array of registered antidepressants available. In recent years there has been a surge in the popularity of natural or alternative medications. Despite this growing popularity, there is limited evidence for the effectiveness of many of these natural treatments. S-adenosyl-L-methionine (SAMe) is one of the better studied of the natural remedies. SAMe is a methyl donor and is involved in the synthesis of various neurotransmitters in the brain. Derived from the amino acid L-methionine through a metabolic pathway called the one-carbon cycle, SAMe has been postulated to have antidepressant properties. A small number of clinical trials with parenteral or oral SAMe have shown that, at doses of 200-1600 mg/d, SAMe is superior to placebo and is as effective as tricyclic antidepressants in alleviating depression, although some individuals may require higher doses. SAMe may have a faster onset of action than do conventional antidepressants and may potentiate the effect of tricyclic antidepressants. SAMe may also protect against the deleterious effects of Alzheimer disease. SAMe is well tolerated and relatively free of adverse effects, although some cases of mania have been reported in bipolar patients. Overall, SAMe appears to be safe and effective in the treatment of depression, but more research is needed to determine optimal doses. Head-to-head comparisons with newer antidepressants should help to clarify SAMe's place in the psychopharmacologic armamentarium.

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Am J Clin Nutr. 2002 Nov;76(5):1151S-7S.
S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis of a
pleiotrophic molecule.
Bottiglieri T.
Baylor University Medical Center, Institute of Metabolic Disease, Dallas, TX 75226, USA. teodorob@baylorhealth.edu

S-Adenosyl-L-methionine (SAMe), a metabolite present in all living cells, plays a central role in cellular biochemistry as a precursor to methylation, aminopropylation, and transsulfuration pathways. As such, SAMe has been studied extensively since its chemical structure was first described in 1952. Decades of research on the biochemical and molecular roles of SAMe in cellular metabolism have provided an extensive foundation for its use in clinical studies, including those on depression, dementia, vacuolar myelopathy, liver disease, and osteoarthritis. This article provides an overview of the biochemical, molecular, and therapeutic effects of this pleiotrophic molecule.

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J ECT. 2002 Sep;18(3):130-7.
Effect of piracetam on ECT-induced cognitive disturbances: a randomized, placebo-controlled, double-blind study.
Tang WK, Ungvari GS, Leung HC.
Department of Psychiatry, Chinese University of Hong Kong, Hong Kong, SAR, China. tangwk@cuhk.edu.hk

Electroconvulsive therapy (ECT) is still the fastest, most effective, and frequently life-saving therapeutic intervention in several forms of depression and some other psychiatric disorders. Transient memory disturbances are frequent after ECT. A randomized, double-blind, placebo-controlled study was conducted to investigate the effects of piracetam on ECT-induced confusion and memory disturbances. Thirty-eight consecutively admitted patients with depressive illness or schizophrenia requiring ECT were given either piracetam or an identical-looking placebo during the period of ECT treatment and for 2 weeks afterward. Daily dosage of piracetam was 7.2 g, given orally for the first 2 weeks while patients underwent ECT (loading phase), followed by 4.8 g for the rest of the study period. Participants were evaluated by standardized clinical rating scales and cognitive psychologic tests 1 to 2 days before ECT, 1 day after their third and sixth ECT treatments, and 2 weeks after they had completed their ECT courses. Piracetam had no significant effect in preventing ECT-induced memory disturbances. All clinical ratings were consistently, albeit not significantly, better in the piracetam group, suggesting that piracetam may have augmented the effects of ECT.

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Gerontology. 2002 Nov-Dec;48(6):392-400.
Late-life depression: rationalizing pharmacological treatment options.
Montgomery SA.
Imperial College School of Medicine, London, UK. stuart@montgomery.demon.co.uk

BACKGROUND: Depressive symptoms in late life are a major concern as they increase disability and aggravate existing medical conditions. Depression is underrecognised and undertreated in the elderly, be it due to somatic symptoms, comorbid physical illness or anxiety, or because it is accepted as a normal feature of ageing. There is little doubt that effective and well-tolerated antidepressant therapy is required. OBJECTIVE: This paper reviews the antidepressant treatment options for late-life depression (selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mixed noradrenergic and serotonergic agents), in terms of their efficacy, safety and pharmacokinetics in elderly patients. RESULTS: In addition to proven efficacy, selection of an antidepressant agent for late-life depression must be based on an understanding of safety and pharmacokinetic issues associated with each agent. Comorbid conditions and lifestyle characteristics of the elderly that are different to those encountered in the younger adult population should also be considered. CONCLUSIONS: To date, published clinical evidence in the elderly suggests that the first-choice agents for treating late-life depression are the SSRIs. Copyright 2002 S. Karger AG, Basel

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Prim Care. 2002 Jun;29(2):339-60, vii.
Anxiety, depression, and insomnia.
Larzelere MM, Wiseman P.
Department of Family Medicine, Louisiana State University Health Sciences Center, School of Medicine, 200 West Esplanade Avenue, Suite 510, Kenner, LA 70065, USA. mlarze@lsuhsc.edu

Evidence for alternative treatments for depression, anxiety, and insomnia are reviewed in this article. Treatment of depression with St. John's wort, L-tryptophan, 5-hydroxytryptophan, S-adenosylmethionine, dehydroepiandosterone, folate, exercise, acupuncture, and meditation are examined. Evidence for the efficacy of kava kava, exercise, relaxation therapies, and acupuncture in treatment anxiety is reviewed. The use of valerian, melatonin, chamomile, passionflower, exercise, acupuncture, and behavioral therapies (i.e., sleep restriction, stimulus control, relaxation, and sleep hygiene) for insomnia is discussed.

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Expert Opin Investig Drugs. 2002 Oct;11(10):1477-86.
Escitalopram.
Burke WJ.
University of Nebraska Department of Psychiatry, 985580 Nebraska Medical Center, Omaha, NE 68198-5580, USA. wjburke@unmc.edu

Escitalopram oxalate (S-citalopram, Lexapro), a selective serotonin re-uptake inhibitor antidepressant which is the S-enantiomer of citalopram, is in clinical development worldwide for the treatment of depression and anxiety disorders. Preclinical studies demonstrate that the therapeutic activity of citalopram resides in the S-isomer and that escitalopram binds with high affinity to the human serotonin transporter. Conversely, R-citalopram is approximately 30-fold less potent than escitalopram at this transporter. Escitalopram has linear pharmacokinetics, so that plasma levels increase proportionately and predictably with increased doses and its half-life of 27 - 32 h is consistent with once-daily dosing. In addition, escitalopram has negligible effects on cytochrome P450 drug-metabolising enzymes in vitro, suggesting a low potential for drug-drug interactions. The efficacy of escitalopram in patients with major depressive disorder has been demonstrated in multiple short-term, placebo-controlled clinical trials, three of which included citalopram as an active control, as well as in a 36-week study evaluating efficacy in the prevention of depression relapse. In these studies, escitalopram was shown to have robust efficacy in the treatment of depression and associated symptoms of anxiety relative to placebo. Efficacy has also been shown in treating generalised anxiety disorder, panic disorder and social anxiety disorder. Results also suggest that, at comparable doses, escitalopram demonstrates clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram. Analysis of the safety database shows a low rate of discontinuation due to adverse events, and there was no statistically significant difference between escitalopram 10 mg/day and placebo in the proportion of patients who discontinued treatment early because of adverse events. The most common adverse events associated with escitalopram which occurred at a rate greater than placebo include nausea, insomnia, ejaculation disorder, diarrhoea, dry mouth and somnolence. Only nausea occurred in > 10% of escitalopram-treated patients.

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Zh Nevrol Psikhiatr Im S S Korsakova. 2002;102(9):22-5.
[Cognitive behavioral therapy of residual symptoms in patients with juvenile depression]
[Article in Russian]
Kaz'mina OIu, Oleichik IV, Zeziulia TN, Krylova ES.

There were forty patients (mean age 20.7 years) who met the ICD-10 criteria of diagnosis of affective disorder (items F31-F33)--juvenile depression, successfully treated with antidepressants in psychiatric hospital and later on maintenance therapy for correction of residual symptoms. The duration of follow-up study was 2 years. All the patients were randomised into two groups, the first one receiving psychopharmacotherapy combined with cognitive behavioural therapy and the second--only the former one. In both groups, the antidepressant dosing was continuously decreased up to complete withdrawal. In the first group, patients revealed significantly fewer residual symptoms after antidepressants treatment compared with the second group, which was assigned only to psychopharmacotherapy. Also, depression relapse frequency tended to be lower in the first group than in the second one (15% vs 35%) but the differences were insignificant. The authors emphasize that further studies of cognitive behavioural therapy in depression relapse prevention are needed.

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CNS Drug Rev. 2002 Fall;8(3):283-308.
Moclobemide: evolution, pharmacodynamic, and pharmacokinetic properties.
Bonnet U.
Rheinische Kliniken Essen, Department of Psychiatry and Psycotherapy, University of Essen, Essen, Germany. udo.bonnet@uni-essen.de.

The benzamide moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA). It has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively in anxiety disorders. While clinical aspects will be presented in a subsequent review, this article focuses primarily on moclobemide's evolution, pharmacodynamic and pharmacokinetic properties. In particular, the effects on neurotransmission and intracellular signal transduction, the neuroendocrine system, the tyramine pressure response and animal models of depression are surveyed. In addition, other CNS effects are reviewed with special respect to experimental serotonergic syndrome, anxiolytic and antinociceptive activity, sleep, cognition and driving performance, neuroprotection and seizures.

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J Clin Psychopharmacol. 2002 Oct;22(5):474-80.
Effects of adding cognitive therapy to fluoxetine dose increase on risk of relapse and residual depressive symptoms in continuation treatment of major depressive disorder.
Perlis RH, Nierenberg AA, Alpert JE, Pava J, Matthews JD, Buchin J, Sickinger AH, Fava M.
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, 02114, USA. rperlis@partners.org

Patients with major depressive disorder remain at risk for relapse following remission and often continue to experience subthreshold symptoms. This study compared the rate of relapse of major depressive disorder and the prevalence of residual depressive symptoms during the continuation phase for patients treated with fluoxetine dose increase alone or in combination with cognitive therapy. A total of 132 outpatients with major depressive disorder who achieved remission with 8 weeks of treatment with fluoxetine 20 mg had the dose increased to 40 mg. They were randomized to receive cognitive therapy or medication management alone and were followed for up to 28 weeks for depressive relapse and change in depressive symptoms. A total of 47 (35.6%) out of 132 patients did not complete the 28-week continuation phase. Rates of discontinuation or relapse did not differ significantly between the groups. Change in residual symptoms or wellbeing as measured by Hamilton Depression Scale score or Symptom Questionnaire self-report also did not differ between groups. In this sample of outpatients in continuation phase treatment for major depressive disorder, the combination of cognitive therapy and fluoxetine 40 mg failed to yield any significant benefit in symptoms or relapse rates over fluoxetine 40 mg alone during 28 weeks of follow-up.

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Eur J Clin Pharmacol. 2002 Sep;58(6):379-86. Epub 2002 Aug 10.
Fluoxetine dose and outcome in antidepressant drug trials.
Barbui C, Hotopf M, Garattini S.
"Mario Negri" Institute for Pharmacological Research, Milan, Italy. corrado.barbui@univr.it

OBJECTIVE: One potential for bias in the evaluation of a new drug is the dose used, both for the new compound and for the reference drug. The present study compared fluoxetine dose and outcome in trials in which fluoxetine was the experimental drug with trials in which it was the comparator. METHODS: Systematic review of randomised controlled trials comparing fluoxetine with any other antidepressant in depressive patients. Studies were allocated to one of the following two groups: group 1 = fluoxetine was the experimental drug; group 2 = fluoxetine was the control drug. Trials were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register. RESULTS: The systematic search yielded 103 randomised trials. Studies in which fluoxetine was the experimental drug adopted a higher dose regimen than group-2 studies. In the efficacy analysis, the weighted rate of fluoxetine responders was 70.1% (confidence interval 67.4%, 72.8%) in group-1 studies and 57.9% (57.2%, 58.7%) in group-2 studies. In the effectiveness analysis, the weighted rate of fluoxetine responders was 56.4% (55.3%, 57.6%) in group-1 studies and 51.9% (51.2%, 52.7%) in group-2 studies. The weighted rate of fluoxetine dropouts was higher in group-1 studies. CONCLUSION:. Fluoxetine dose and outcome changed according to whether this drug was used as a new compound or as a reference.

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Sports Med. 2002;32(12):741-60.
Exercise and the treatment of clinical depression in adults: recent findings and future directions.
Brosse AL, Sheets ES, Lett HS, Blumenthal JA.
Department of Psychology, University of Colorado, Bolder, Colorado, USA.

This article critically reviews the evidence that exercise is effective in treating depression in adults. Depression is recognised as a mood state, clinical syndrome and psychiatric condition, and traditional methods for assessing depression (e.g. standard interviews, questionnaires) are described. In order to place exercise therapy into context, more established methods for treating clinical depression are discussed. Observational (e.g. cross-sectional and correlational) and interventional studies of exercise are reviewed in healthy adults, those with comorbid medical conditions, and patients with major depression. Potential mechanisms by which exercise may reduce depression are described, and directions for future research in the area are suggested. The available evidence provides considerable support for the value of exercise in reducing depressive symptoms in both healthy and clinical populations. However, many studies have significant methodological limitations. Thus, more data from carefully conducted clinical trials are needed before exercise can be recommended as an alternative to more traditional, empirically validated pharmacological and behavioural therapies.

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Cleve Clin J Med. 2002 Sep;69(9):670, 672-3, 677-8.
The case for hormone replacement: new studies that should inform the debate.
Thacker HL.
Section of Women's Health, Women's Health Center, The Cleveland Clinic Foundation, OH 44195, USA. thackeh@ccf.org

The Women's Health Initiative found that the risks of hormone replacement therapy (HRT) exceeded its benefits in a large group of older postmenopausal women, but did not consider the efficacy of HRT in relieving vasomotor symptoms. Another recent study found that low-dose HRT was as effective as standard-dose HRT while causing fewer side effects. Smaller studies suggest that HRT may improve depression. HRT is not to be used for cardiovascular risk reduction. Genetic testing may point the way to more rational use of HRT.

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Phytomedicine. 2002 Jul;9(5):468-74.
Clinical trials with hypericum extracts in patients with depression--results, comparisons, conclusions for therapy with antidepressant drugs.
Schulz V.
V.Schulz.Berlin@t-online.de

By the spring of 2002, results from 34 controlled, double-blind trials of Hypericum extracts in some 3000 patients, predominantly with mild to moderate forms of depression, had been published. An overview is given of the studies conducted since 1990. In the majority of them, the efficacy criterion (primary endpoint) was the score and/or response rate on the Hamilton Rating Scale of Depression (HAMD). In ten studies, based on extracts prepared with 50% or 60% ethanol in water (V/V), the dosages ranged from 300 mg to 1050 mg of extract per day. Five of the ten studies were placebo-controlled and in all five cases, the Hypericum extract was shown to be significantly superior. Results with Hypericum were as good or even better than with imipramine or fluoxetine. In the period since 1990, a total of twelve controlled trials have been published with one particular extract prepared with 80% methanol in water (V/V), of which six were placebo-controlled, two compared Hypericum with imipramine and one each with maprotiline, amitriptyline, sertraline or light therapy. Dosages ranged from 450-1200 mg extract per day. Statistical analysis of the total Hamilton scores showed significant differences between Hypericum extract and placebo in four of the six placebo-controlled studies and a trend in favour of the active treatment in the other two. Of the five comparative trials against four different synthetic antidepressants, amitriptyline was significantly superior to Hypericum after six weeks of therapy, whilst there were no significant differences in treatment outcome between Hypericum and the other synthetics in the remaining four studies. The results of the trials conducted to date show no major differences in efficacy of the alcoholic extracts. Taking all the results into account, it can be assumed that the threshold dose for efficacy against individual symptoms and complaints that occur in the course of the depressive illness could be about 300 mg of extract per day. In the medically supervised treatment of mild to moderate depression, doses of approximately 500-1000 mg of extract per day of these preparations of St. John's Wort are of comparable efficacy to synthetic antidepressants in their normally prescribed dosages.

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Eur Neuropsychopharmacol. 2002 Oct;12(5):433-44.
Enantiomers' potential in psychopharmacology--a critical analysis with special emphasis on the antidepressant escitalopram.
Baumann P, Zullino DF, Eap CB.
Departement Universitaire de Psychiatrie Adulte, Unite de Biochimie et Psychopharmacologie Clinique, Hopitalde Cery, CH-1008, Prilly-Lausanne, Switzerland. pierre.baumann@inst.hospvd.ch

Stereochemistry is now influencing most areas of pharmacotherapy, with a growing awareness in the field of psychiatry and, more specifically, depression. This is due to the fact that the enantiomers of many chiral drugs may have distinct pharmacological, pharmacokinetic and/or pharmacogenetic profiles. Consequently, in some instances there may be an advantage in using a single enantiomer over the racemic form-thus providing a basis for the development of new therapeutic agents, as well as the potential to improve current treatments. This review highlights some of the potential advantages and disadvantages that using single enantiomers might offer. The principles are exemplified through reference to the stereoselective properties of several established chiral psychotropic drugs, including thioridazine, methadone, trimipramine, mianserin, mirtazapine, fluoxetine and citalopram. Emphasis is given to the treatment of depression and how the potential of one pure enantiomer-escitalopram, the S-enantiomer of the selective serotonin reuptake inhibitor citalopram-appears to be fulfilling its preclinical promise in the clinic.

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Eur Arch Psychiatry Clin Neurosci. 2002 Jun;252(3):105-9.
Intravenous antidepressant treatment: focus on citalopram.
Kasper S, Muller-Spahn F.
Department of General Psychiatry, University of Vienna, Wahringer Gurtel 18-20, 1090 Wien, Austria. SK@akh-wien.ac.at

During the last decade, the number of patients who consult primary care physicians or psychiatrists for symptoms of depression has doubled. The majority of depressed patients are prescribed oral medication; however, in several European countries antidepressant therapy may be initiated with a daily intravenous infusion. The choice of intravenous antidepressants was previously limited to agents such as dibenzepine, doxepin, clomipramine and viloxazine. More recently, the selective serotonin reuptake inhibitor (SSRI) citalopram has been administered as an intravenous infusion to severely depressed patients. The results from both open and double-blind clinical studies with intravenous citalopram suggest that it is an effective and well-tolerated treatment for depression. Moreover, when treatment is initiated by infusion and continued orally, citalopram is at least as effective as clomipramine, doxepin and viloxazine. As with oral treatment, adverse events experienced by patients are mild to moderate in severity with 50 % of patients reporting no adverse events. The high bioavailability of citalopram indicates that the switch from intravenous to oral citalopram would prevent a deterioration of symptoms as plasma drug concentrations would be maintained. Thus citalopram, the only SSRI available as an intravenous formulation, may be a useful addition for the treatment of severely depressed patients who may benefit from more intensive therapy. The aim of this paper is to review available data detailing the clinical outcome of intravenously administered citalopram in depressed patients.

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Int J Clin Pract. 2002 Jul-Aug;56(6):434-9.
Healthcare expenditure in patients treated with venlafaxine or selective serotonin reuptake inhibitors for depression and anxiety.
Wan GJ, Crown WH, Berndt ER, Finkelstein SN, Ling D.
Wyeth Research, Philadelphia, PA 19087, USA.

We compared healthcare expenditure over a six-month period following initiation of therapy with either venlafaxine (immediate and extended-release) or a selective serotonin reuptake inhibitor (SSRI) in depressed patients with or without anxiety. Patients beginning treatment for a new depressive episode were identified retrospectively using the administrative data of the MEDSTAT MarketScan database for the period 1994-1999. Before beginning therapy, patients prescribed venlafaxine had more non-mental illnesses (0.85 vs 0.76; p<0.01) and hospitalisations for mental illness (0.53 vs 0.29; p<0.05) than patients prescribed SSRIs. In the six months after initiating treatment, venlafaxine was associated with lower hospitalisation expenditure for non-mental illness ($177 vs $526; p<0.01) than SSRIs, although total healthcare expenditure was not significantly different. Venlafaxine was associated with a 50% decrease in the odds of hospitalisation for non-mental illness compared with SSRIs, with significantly lower inpatient expenditure.

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Ugeskr Laeger. 2002 Jun 24;164(26):3435-9.
[The effect of psychotherapy on depression]
[Article in Danish]
Jorgensen MB, Dam OH, Bolwig TG.
Psykiatrisk afdeling O, Rigshospitalet, Blegdamsvej 9, DK-2100 Kobenhavn o.

Over the last decades, numerous studies of the efficacy of psychotherapy on major depression have been carried out. They provide evidence of the effectiveness of cognitive therapy and interpersonal therapy in the treatment of mild to moderate depression. The effectiveness of psychotherapy in in-patients and patients with severe depression has not been documented. Maintenance interpersonal therapy may contribute to prevent new episodes in recurrently depressive patients, where promising studies also indicate that cognitive therapy has a preventive effect on future depressions. This calls for larger and better controlled studies.

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Recenti Prog Med. 2002 Jun;93(6):343-5.
[Long-term treatment of depression: there is more than drugs]
[Article in Italian]
Fava GA, Ruini C.
Dipartimento di Psicologia, Alma Mater Studiorum, Universita, Bologna. dip@psibo.unibo.it

Recent studies have emphasized the chronic nature of depressive disorder, and the need for endorsing the same treatment protocols used for other chronic disease, such as diabetes. But duration of treatment does not seem to affect long-term prognosis of patients with depression, once the drug is stopped. Despite treating depression effectively in the short-term, antidepressant drugs may worsen its course. Treatment of depression by pharmacological means is likely to leave residual symptoms in most patients. Such symptoms are important risk factors for relapse. In randomised controlled studies, cognitive behavioural treatment of residual symptoms significantly improved long-term outcome of recurrent depression. Indeed, depressive disorder has a chronic nature, but antidepressants are not the only possible treatment strategy. Cognitive-behavioral psychotherapy is an alternative, which is effective in engendering a complete and lasting recovery in patients with depression.

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Cochrane Database Syst Rev. 2002;(2):CD003493.
Transcranial magnetic stimulation for treating depression.
Martin JL, Barbanoj MJ, Schlaepfer TE, Clos S, Perez V, Kulisevsky J, Gironell A.
Iberoamerican Cochrane Centre, Department of Epidemiology, Hospital de la Santa Creu i Sant Pau, Sant Antoni M feminine Claret, 171, Barcelona, Catalunya, Spain, 08041. jrodriguezma@hsp.santpau.es

BACKGROUND: Transcranial magnetic stimulation can either excite or inhibit cortical areas of the brain, depending on whether the speed of the repetitive stimulation is applied at high or low frequencies. It has been used for physiological studies and it has also been proposed as a treatment for depression. OBJECTIVES: To assess the clinical efficacy and safety of transcranial magnetic stimulation for treating depression. SEARCH STRATEGY: An electronic search was performed including the Cochrane Collaboration Depression, Neurosis and Anxiety Review Group trials register (last searched June, 2001), the Cochrane Controlled Trials Register (Issue 2, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), PsycLIT (1980-2001), and bibliographies from reviewed articles. Unpublished data and grey literature were searched through personal communications with researchers. SELECTION CRITERIA: Randomised controlled trials assessing the therapeutic efficacy and safety of transcranial magnetic stimulation for depression. DATA COLLECTION AND ANALYSIS: All reviewers independently extracted the information and verified it by cross-checking. Disagreements were resolved through discussion. Continuous data: When similar studies were grouped, the overall standardised mean difference was calculated under a fixed effect model weighted by the inverse variance method with 95% confidence intervals. (In the presence of statistical heterogeneity, a random effects model was to be used.) MAIN RESULTS: Sixteen trials were included in the review and fourteen contained data in a suitable form for quantitative analysis. Most comparisons did not show differences between rTMS and other interventions. No difference was seen between rTMS and sham TMS using the Beck Depression Inventory or the Hamilton Depression Rating Scale, except for one time period (after two weeks of treatment) for left dorsolateral prefrontal cortex and high frequency; and also for right dorsolateral prefrontal cortex and low frequency, both in favour of rTMS and both using the Hamilton scale. Comparison of rTMS (left dorsolateral prefrontal cortex and high frequency) with electroconvulsive therapy showed no difference except for psychotic patients after two weeks treatment, using the Hamilton scale, which indicated that electroconvulsive therapy was more effective than rTMS. REVIEWER'S CONCLUSIONS: The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.

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Adv Ther. 2002 Jan-Feb;19(1):43-52.
Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression.
Behnke K, Jensen GS, Graubaum HJ, Gruenwald J.
PhytoPharm Consulting, Institute for Phytopharmaceuticals, Berlin, Germany.

In a randomized, controlled, double-blind trial, 70 patients (mean age, 49.7 years) suffering from mild to moderate depression received one tablet of either St. John's Wort (Hypericum perforatum) extract (Calmigen) or fluoxetine hydrochloride (Prozac) twice a day for 6 weeks. Efficacy was determined according to the 17-item Hamilton Rating Scale for Depression (HAMD), the von Zerssen depression scale (DS), Clinical Global Impression (CGI), and patients' overall evaluation. Significant decreases (P<.001) of 50% in the Hypericum group and 58% in the fluoxetine group in the HAMD score and of 42% and 52% on the DS spoke to the efficacy of both medications. The Hypericum extract achieved 83% of the efficacy of fluoxetine on the HAMD and 78% on the DS. Assessments by physicians (CGI) and patients indicated considerable improvement with no between-treatment differences. Of the 9 dropouts (13%), 2 in the Hypericum group and 2 in the fluoxetine group were due to adverse reactions. Safety evaluations demonstrated only minor changes. The Hypericum preparation tested in this study is therapeutically equivalent to fluoxetine and is therefore a rational alternative to synthetic antidepressants.

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Life Sci. 2002 May 17;70(26):3077-96.
St. John's wort and depression: efficacy, safety and tolerability—an update.
Bilia AR, Gallori S, Vincieri FF.
Department of Pharmaceutical Science, University of Florence, Via Gino Capponi 9, 50121, Firenze, Italy. ar.bilia@unifi.it

St. John's wort (Hypericum perforatum L.) is a medicinal plant traditionally used, both externally and internally, in all Europe for many pathologies. Paracelsus named it "arnica of the nerves" because of its empirical use in nervous diseases. In the last two decades many studies have proved the efficacy of some St. John's wort extracts in mild to moderate depression and it has been successful as an antidepressant both in Europe and the US. Its high efficacy and tolerability is unquestionable and from the clinical studies the activity is comparable to other antidepressants while lacking major side effects, making it a safe antidepressant.However, recently its potential to induce the metabolism of co-administered medications has been reported because it may potentate certain enzymes of the cytochrome P450 enzyme system. This resulted in a lowering of serum concentration of a number of concomitant drugs, including warfarin, digoxin, theophylline, cyclosporin, and indinavir. Many drugs and also several common foods and drinks can influence this enzyme system. So, even if its safety has been well established, physicians should be aware that St. John's wort administration might significantly affect other prescribed medicines.

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Am J Geriatr Psychiatry. 2002 May-Jun;10(3):344-7.
Citalopram treatment of minor depression in elderly men: an open pilot study.
Kasckow JW, Welge J, Carroll BT, Thalassinos A, Mohamed S.
Department of Psychiatry, University of Cincinnati College of Medicine, and the Cincinnati VAMC, Cincinnati, OH 45267-0559, USA.

Antidepressant pharmacotherapy in elderly patients is challenging. The authors examined the use of citalopram to treat late-life minor depression. Ten men (mean age: 73+/-2 years) with DSM-IV Minor Depression were administered citalopram 20 mg/day. Efficacy was measured with the Geriatric Depression Scale (GDS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions of Severity (CGI-S) scales. Citalopram was well tolerated, and GDS, MADRS, and CGI-S scores decreased after 12 weeks. These findings indicate that citalopram is safe and effective in the treatment of late-life minor depression.
 

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