Panic Disorder Research:
2002-2006
     
J Clin Psychiatry. 2006 Oct;67(10):1573-6.
Safety and efficacy of levetiracetam for patients with panic disorder: results of an open-label, fixed-flexible dose study.
Papp LA.
>From Columbia University, New York State Psychiatric Institute, and Hillside Hospital, New York, N.Y.

OBJECTIVE: To examine the safety and efficacy of the anticonvulsant levetiracetam in the treatment of patients with panic disorder. METHOD: In an open-label, fixed-flexible dose study, 18 patients with panic disorder with or without agoraphobia (DSM-IV diagnostic criteria) were treated with levetiracetam for 12 weeks. Outcome was assessed with standard rating instruments (Clinical Global Impressions-Severity of Illness scale [CGI-S], Clinical Global Impressions-Improvement scale [CGI-I], and the 14-item Hamilton Rating Scale for Anxiety [HAM-A]) and by the number of panic attacks during the previous week. The study was conducted in 2 outpatient clinics in New York City from January 2004 through July 2005. RESULTS: Of the 13 patients completing the study, 11 were rated "very much" or "much" improved on the CGI-I. Panic attack frequency, anxiety (HAM-A), and global severity (CGI-S) ratings also demonstrated significant improvement (all p < .00). For most patients, clinical benefits were apparent after only 1 to 2 weeks of treatment. Levetiracetam was well tolerated with minimal side effects. CONCLUSION: Given its favorable pharmacoki-netics, side effect profile, and, if confirmed, early onset of action and efficacy, levetiracetam might represent significant progress in the pharmacologic management of panic disorder.

-----

Behav Res Ther. 2006 Oct 25; [Epub ahead of print]
Cognitive behavioral therapy for panic disorder and comorbidity: More of the same or less of more?
Craske MG, Farchione TJ, Allen LB, Barrios V, Stoyanova M, Rose R.
Department of Psychology, UCLA., 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA.

This study compared the effects of a higher dose of cognitive behavioral therapy (CBT) for panic disorder versus CBT for panic disorder combined with "straying" to CBT for comorbid disorders in individuals with a principal diagnosis of panic disorder with or without agoraphobia. Sixty-five participants were randomly assigned to one of two treatment conditions, either CBT focused solely upon panic disorder and agoraphobia or CBT that simultaneously addressed panic disorder and agoraphobia and, to a lesser degree, the most severe comorbid condition. Results indicated a significant reduction in panic disorder severity and a decline in severity of comorbid diagnoses across both treatment conditions. However, individuals receiving CBT focused only on panic disorder were more likely to meet high end-state functioning at post-treatment, even in intent-to-treat analyses, and report zero panic attacks at the 1-year follow-up, although this effect was not retained in intent-to-treat analyses. At follow-up, CBT focused only on panic disorder yielded more substantial improvement in the most severe baseline comorbid condition, although not in intent-to-treat analyses, and a greater proportion of individuals in this treatment condition were rated as having no comorbid diagnoses, even in intent-to-treat analyses. These findings raise the possibility that remaining focused on CBT for panic disorder may be more beneficial for both principal and comorbid diagnoses than combining CBT for panic disorder with 'straying' to CBT for comorbid disorders.

-----

CNS Spectr. 2006 Oct;11(10 Suppl 12):29-33.
Efficacy of combined pharmacotherapy and psychotherapy versus monotherapy in the treatment of anxiety disorders.
Black DW.
University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.

Anxiety disorders in the United States are prevalent, widespread, and disabling. These illnesses may account for almost one third of the $148 billion total mental health bill each year. Pharmacologic options include tricyclic antidepressants, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and anxiolytics. Psychological treatments include cognitive-behavioral therapy (CBT), cognitive therapy, exposure, and ritual prevention therapies. Despite insufficient evidence, many experts recommend combined treatment, generally medication with CBT. A literature review was conducted to examine studies with random assignment, adequate methods and sample sizes, blind assessments, sufficient dosages and durations of treatment, and satisfactory reporting of data, to determine whether combined treatment was superior to monotherapy. Twenty-six randomized clinical trials were identified; nine met review criteria. A review of relevant studies could not confirm the superiority of combined treatment over monotherapy. In one of four studies of obsessive-compulsive disorder, combined treatment produced better results than monotherapy. There was no evidence of superiority for combined therapy over monotherapy for the treatment of social phobia or generalized anxiety disorder. There were no studies that met review criteria for either specific phobia or posttraumatic stress disorder (PTSD). With panic disorder, there was evidence that combined treatment might actually lead to worse outcome. Combined treatment is commonly recommended, but empirical support is limited. More research is needed. There are few well-designed studies, and little data regarding PTSD and specific phobias.

-----

Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004515.
Valerian for anxiety disorders.
Miyasaka LS, Atallah AN, Soares BG.
Universidade Federal de Sao Paulo, Emergency medicine department, Sao Paulo, Brazil. lincoln.miyasaka@terra.com.br

BACKGROUND: Anxiety disorders are very common mental health problems in the general population and in primary care settings. Herbal medicines are popular and used worldwide and might be considered as a treatment option for anxiety if shown to be effective and safe. OBJECTIVES: To investigate the effectiveness and safety of valerian for treating anxiety disorders. SEARCH STRATEGY: Electronic searches: The Cochrane Collaboration Depression, Anxiety and Neurosis Cochrane Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) searched on 04/08/2006, MEDLINE, Lilacs. References of all identified studies were inspected for additional studies. First authors of each included study, manufacturers of valerian products, and experts in the field were contacted for information regarding unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials of valerian extract of any dose, regime, or method of administration, for people with any primary diagnosis of general anxiety disorder, anxiety neurosis, chronic anxiety status, or any other disorder in which anxiety is the primary symptom (panic disorder, obsessive compulsive disorder, social phobia, agoraphobia, other types of phobia, postraumatic stress disorder). Effectiveness was measured using clinical outcome measures and other scales for anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, extracted and entered data, and performed the trial quality assessments. Where disagreements occurred, the third review author was consulted. Methodological quality of included trials was assessed using Cochrane Handbook criteria. For dichotomous outcomes, relative risk (RR) was calculated, and for continuous outcomes, the weighted mean difference (WMD) was calculated, with their respective 95% confidence intervals. MAIN RESULTS: One RCT involving 36 patients wih generalised anxiety disorder was eligible for inclusion. This was a 4 week pilot study of valerian, diazepam and placebo. There were no significant differences between the valerian and placebo groups in HAM-A total scores, or in somatic and psychic factor scores. Similarly, there were no significant differences in HAM-A scores between the valerian and diazepam groups, although based on STAI-Trait scores, significantly greater symptom improvement was indicated in the diazepam group. There were no significant differences between the three groups in the number of patients reporting side effects or in dropout rates. AUTHORS' CONCLUSIONS: Since only one small study is currently available, there is insufficient evidence to draw any conclusions about the efficacy or safety of valerian compared with placebo or diazepam for anxiety disorders. RCTs involving larger samples and comparing valerian with placebo or other interventions used to treat of anxiety disorders, such as antidepressants, are needed.

-----

J Clin Psychiatry. 2006 Sep;67(9):1327-40.
Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review.
Gao K, Muzina D, Gajwani P, Calabrese JR.
Department of Psychiatry, the Bipolar Disorders Research Center, University Hospitals of Cleveland/Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA. keming.gao@uhhs.com

OBJECTIVE: The efficacy of antipsychotics in the treatment of primary or comorbid anxiety disorders or anxiety symptoms in major depressive disorder or bipolar disorder was reviewed. DATA SOURCES: English-language literature cited in MEDLINE from January 1, 1968, to December 31, 2005, was searched with the keywords anxiety disorder, anxiety symptoms, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, bipolar disorder, major depressive disorder, Hamilton Rating Scale for Anxiety, antipsychotics, typical antipsychotics, atypical antipsychotics, fluphenazine, haloperidol, perphenazine, pimozide, thiothixene, trifluoperazine, loxapine, molindone, chlorpromazine, mesoridazine, thioridazine, fluspirilene, penfluridol, pipothiazine, flupenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, amisulpride, and clinical trial. Randomized, double-blind, placebo-controlled trials and open-label studies with a minimum of 20 subjects with a DSM-III/IV or ICD-10 diagnosis of anxiety disorder and studies without a DSM-III/IV or ICD-10 diagnosis of anxiety disorder but with Hamilton Rating Scale for Anxiety (HAM-A) scores as an outcome were prioritized. Studies on bipolar disorder or major depressive disorder with the analysis of changes in anxiety symptoms were reviewed. Early studies on neurosis/ anxiety or anxious depression without a HAM-A component were also reviewed. DATA SYNTHESIS: Six trials in primary generalized anxiety disorder (GAD), 15 in refractory obsessive-compulsive disorder (OCD), 8 in posttraumatic stress disorder (PTSD), 6 in neurosis with the HAM-A, 1 in social phobia, and 2 in anxiety symptoms in bipolar depression were identified. Low doses of trifluoperazine were superior to placebo in the treatment of GAD. Most of the less well-designed studies showed that other typical antipsychotics might be superior to placebo or as effective as benzodiazepines in the treatment of GAD and other anxiety conditions. In most studies, risperidone, olanzapine, and quetiapine augmentation to antidepressants was superior to placebo in treating refractory OCD and PTSD. Both olanzapine and quetiapine significantly reduced anxiety compared to placebo in studies of bipolar depression. CONCLUSION: Except for trifluoperazine, there is no large, well-designed study of antipsychotics in the treatment of primary or comorbid anxiety symptoms or disorders. The efficacy of these agents in various anxiety conditions needs to be further investigated with large, well-designed comparison studies.

-----

J Affect Disord. 2006 Sep 29; [Epub ahead of print]
A pragmatic, unblinded randomised controlled trial comparing an occupational therapy-led lifestyle approach and routine GP care for panic disorder treatment in primary care.
Lambert RA, Harvey I, Poland F.
School of Allied Health Professions, University of East Anglia, Norwich, Norfolk, England, NR4 7TJ, UK.

BACKGROUND: Treated anxiety increased in the UK by over 30% since 1994. Medication and psychological treatment is most common, but outcomes are sometimes poor, with high relapse rates. Lifestyle has a potential role in treatment, but is not considered in clinical guidelines. Panic disorder is potentially influenced by lifestyle factors. METHODS: 16 week unblinded pragmatic randomised controlled trial in 15 East of England primary care practices (2 Primary Care Trusts). Participants met DSM-IV criteria for panic disorder with/without agoraphobia. Follow-up at 20 weeks and 10 months. Control arm, unrestricted routine GP care. Trial Arm, Occupational therapy-led lifestyle treatment comprising: lifestyle review of fluid intake, diet pattern, exercise, caffeine, alcohol and nicotine; negotiation of positive lifestyle changes; monitoring and review of impact of changes. Primary outcome measure: Beck Anxiety Inventory. DATA ANALYSIS: Intention-to-treat analysis provided between-group comparisons using analysis of co-variance. Bonferroni method to adjust p-values. RESULTS: From 199 referrals, 36 GP care and 31 lifestyle arm patients completed to final follow-up. Significantly lower lifestyle arm BAI scores at 20 weeks (p<0.001), non-significant (p=0.167) at 10 months after Bonferroni correction. 63.6% lifestyle arm, and 40% GP arm patients (p=0.045) panic-free at 20 weeks; 67.7% and 48.5% (p=0.123) respectively at 10 months. LIMITATIONS: Final study size/power calls for caution in interpreting findings. CONCLUSIONS: A lifestyle approach may provide a clinically effective intervention at least as effective as routine GP care, with significant improvements in anxiety compared with routine GP care at the end of treatment. Further study is required before suggesting practice changes.

-----

Lancet. 2006 Sep 16;368(9540):1023-32.
Panic disorder.
Roy-Byrne PP, Craske MG, Stein MB.
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine at Harborview Medical Center, Seattle, WA 98104-2499, USA. roybyrne@u.washington.edu

Panic disorder is a common mental disorder that affects up to 5% of the population at some point in life. It is often disabling, especially when complicated by agoraphobia, and is associated with substantial functional morbidity and reduced quality of life. The disorder is also costly for individuals and society, as shown by increased use of health care, absenteeism, and reduced workplace productivity. Some physical illnesses (eg, asthma) commonly occur with panic disorder, and certain lifestyle factors (eg, smoking) increase the risk for the disorder, but causal pathways are still unclear. Genetic and early experiential susceptibility factors also exist, but their exact nature and pathophysiological mechanisms remain unknown. Despite an imprecise, although increased, understanding of cause, strong evidence supports the use of several effective treatments (eg, pharmacological, cognitive-behavioural). The adaptation and dissemination of these treatments to the frontlines of medical-care delivery should be urgent goals for the public-health community.

-----

Drug Discov Today. 2006 Jul;11(13-14):623-31.
Creating more effective antidepressants: clues from the clinic.
Rasmussen K.
Lilly Research Laboratories, Eli Lilly & Co, Lilly Corporate Center, Indianapolis, IN 46285, USA. rasmussen_kurt@lilly.com

Antidepressant medications have eased the suffering of millions of people. In addition to treating depression, antidepressant drugs also treat several anxiety disorders. Unfortunately, there are problematic limitations with antidepressant agents, including a delayed therapeutic response and insufficient efficacy. Emerging evidence shows that atypical antipsychotic agents can be used as augmentation therapy in patients with poor responses to antidepressants. Future drugs combining key features of antidepressant and atypical antipsychotic agents could offer new promise for patients suffering from obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, generalized anxiety disorder and depression.

-----

J Nerv Ment Dis. 2006 Jun;194(6):440-5.
An open pilot study of interpersonal psychotherapy for panic disorder (IPT-PD).
Lipsitz JD, Gur M, Miller NL, Forand N, Vermes D, Fyer AJ.
Columbia University, Department of Psychiatry, Anxiety Disorders Clinic, New York State Psychiatric Institute, New York, New York, USA.

Interpersonal psychotherapy (IPT) is a time-limited psychotherapy initially developed to treat depression. It has yet to be studied systematically for treatment of panic disorder. We modified IPT for the treatment of panic disorder and tested this treatment in an open clinical trial with 12 patients seeking treatment of DSM-IV panic disorder. Patients were assessed before during and after treatment. At completion of treatment, nine patients (75%) were independently categorized as responders (i.e., rated as much improved or very much improved on the Clinical Global Impression-Change Scale). Substantial improvement was found for panic symptoms, associated anxiety and depressive symptoms, and physical and emotional well-being. Degree of change in this sample approximated that obtained in studies using established treatments such as cognitive behavioral therapy. Results, though preliminary, suggest that IPT may have efficacy as a primary treatment of panic disorder. Further study is warranted.

-----

J Psychiatry Neurosci. 2006 May;31(3):168-176.
The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs.
Chouinard G.
Fernand-Seguin Research Centre, Louis-H. Lafontaine Hospital; Department of Psychiatry, Universite de Montreal; Clinical Psychopharmacology Unit, Allan Memorial Institute, McGill University Health Centre; and Department of Psychiatry, McGill University, Montreal, Que.

Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, such as in panic disorder and mania, were found with the introduction of 2 high-potency benzodiazepines, clonazepam and alprazolam, which were thought to have serotonergic properties. Our initial clinical trials of fluoxetine and sertraline led to their approved indications in the treatment of obsessive-compulsive disorder, and our trials of gabapentin led to new indications in anxiety disorders (generalized anxiety, panic attack and social phobia) and sleep disorders (insomnia).

-----

Depress Anxiety. 2006 May 10; [Epub ahead of print]
Self-rated importance of religion predicts one-year outcome of patients with panic disorder.
Bowen R, Baetz M, D'Arcy C.
Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Cognitive-behavioral therapy and medication are efficacious treatments for panic disorder, but individual attributes such as coping and motivation are important determinants of treatment response. A sample of 56 patients with panic disorder, treated with group cognitive-behavioral therapy, were reassessed 6 months and 12 months after initial assessment. We studied the effect of self-rated importance of religion, perceived stress, self-esteem, mastery, and interpersonal alienation on outcome as measured by the General Severity Index of the Brief Symptom Inventory (BSI.GSI). Importance of religion was a predictor of BSI.GSI symptom improvement at 1 year. Over time, improvement was seen for the religion is very important subgroup in the BSI.GSI and Perceived Stress Scales. This study suggests that one mechanism by which high importance of religion reduces psychiatric symptoms is through reducing perceived stress. Depression and Anxiety 0:1-8, 2006. (c) 2006 Wiley-Liss, Inc.

-----

Expert Opin Pharmacother. 2006 Apr;7(5):545-54.
Pharmacological treatment options for panic disorder in children and adolescents.
Masi G, Pari C, Millepiedi S.
IRCCS Stella Maris Scientific Institute for Child Neurology and Psychiatry, Via dei Giacinti 2 56018 Calambrone (Pi), Italy. gabriele.masi@inpe.unipi.it

Although panic disorder usually emerges in early to middle adulthood, adults with panic disorder often retrospectively report that their panic symptoms began in childhood or early adolescence. The majority of these juvenile cases are being misdiagnosed, and/or do not come to clinical attention. Awareness of early-onset panic disorder, as well as a more precise definition of early signs and possible clinical subtypes, can favour timely diagnosis and treatment, reduce clinical impairment and improve the prognosis of these patients. In the context of a multimodal approach, pharmacological treatment can be helpful. This review focuses on the empirical evidence of pharmacotherapy in early-onset panic disorder, including selective serotonin re-uptake inhibitors, benzodiazepines and tricyclics. The data supporting efficacy are still limited, and no controlled studies are available. Practical guidelines for the management of these patients are provided, including treatment of the most frequent psychiatric comorbidities.

-----

Int Clin Psychopharmacol. 2006 May;21(3):131-42.
Clonazepam in the treatment of psychiatric disorders: an update.
Nardi AE, Perna G.
aInstitute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil bAnxiety Disorders Clinical and Research Unit, Vita-Salute University, Istituto Scientifico Ospedale San Raffaele, Milan, Italy.

An updated overview over the past decade is provided with respect to the use of clonazepam in a variety of psychiatric disorders. The efficacy of clonazepam monotherapy for the short-term treatment of panic disorder (PD) was fully established in two large pivotal multicentre studies in the late 1990s in a total of >800 patients. Other studies support a role for clonazepam, in association with selective serotonin reuptake inhibitors (SSRIs), to accelerate treatment response in PD. Although some longitudinal data suggest an ability to maintain improvement without tolerance for up to 3 years, long-term controlled studies of clonazepam in PD are lacking. Studies have shown that clonazepam can also block CO2-induced panic and improve certain aspects of quality of life in PD. Clonazepam has shown some efficacy in social phobia; however, because this evidence is based on few studies, further studies are warranted before definitive conclusions can be drawn. Finally, evidence for the use of clonazepam in acute mania and as augmentation therapy with SSRIs to accelerate response in depression is examined. The long half-life and higher potency of clonazepam may allow easier discontinuation with fewer withdrawal symptoms compared to other benzodiazepines and studies using a slow clonazepam taper appear promising.

-----

Br J Psychiatry. 2006 Apr;188:305-12.
Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: Systematic review.
Furukawa TA, Watanabe N, Churchill R.
Department of Psychiatry and Cognitive-Behavioural Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. furukawa@med.nagoya-cu.ac.jp.

BACKGROUND: Panic disorder can be treated with psychotherapy, pharmacotherapy or a combination of both. AIMS: To summarise the evidence concerning the short- and long-term benefits and adverse effects of a combination of psychotherapy and antidepressanttreatment. METHOD: Meta-analyses and meta-regressions were undertaken using data from all relevant randomised controlled trials identified by a comprehensive literature search. The primary outcome was relative risk (RR) of response. RESULTS: We identified 23 randomised comparisons (21 trials involving a total of 1709 patients). In the acute-phase treatment, the combined therapy was superior to antidepressant pharmacotherapy (RR=1.24,95% CI1.02-1.52) or psychotherapy (RR=1.16,95% CI1.03-1.30). After termination of the acute-phase treatment, the combined therapy was more effective than pharmacotherapy alone (RR=1.61,95% CI1.23-2.11) and was as effective as psychotherapy (RR=0.96, 95% CI 0.79-1.16). CONCLUSIONS: Either combined therapy or psychotherapy alone may be chosen as first-line treatment for panic disorder with or without agoraphobia, depending on the patient's preferences.

-----

Behav Res Ther. 2006 Mar 16; [Epub ahead of print]
Effects of perceived criticism on anxiety and depression during behavioral treatment of anxiety disorders.
Steketee G, Lam JN, Chambless DL, Rodebaugh TL, McCullouch CE.
Boston University, School of Social Work, 264 Bay State Rd., Boston, MA 02215, USA.

The present study explored the effect of perceived criticism (PC) on levels of anxiety and depression during behavioral treatment among patients diagnosed with obsessive-compulsive disorder (OCD) or panic disorder with agoraphobia (PDA). We posited that patients' perceptions of relatives' criticism and the degree to which they were upset by the criticism (UC) would be related to negative affect and discomfort during exposure. The sample included 75 patients with a primary diagnosis of OCD (n=43) or PDA (n=32) and their participating relatives. Measures of patients' weekly ratings of PC and upset about the criticism, anxious and depressed mood, and subjective discomfort during exposure treatment were analyzed using a mixed model regression approach (SAS Proc Mixed). Patients' anxious and depressed mood predicted greater discomfort during exposure. Patients who were more UC also had higher weekly ratings of anxiety and depression, and more discomfort during exposure sessions. Findings suggest that treatment outcome may be improved by attention to patients' reactions to their interpersonal environment.

-----

Expert Rev Neurother. 2006 Mar;6(3):269-82.
Treatment of anxiety disorders with venlafaxine XR.
Thase ME.
University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. thaseme@upmc.edu

When venlafaxine was introduced in 1994, it was the first of the newer generation antidepressants to be classified as a serotonin norepinephrine reuptake inhibitor (SNRI). An extended release (XR) formulation of venlafaxine, introduced in 1997, subsequently received regulatory approval for treatment of three anxiety disorders: generalized anxiety disorder, social anxiety disorder and panic disorder. Although less extensively studied, venlafaxine XR also appears to have efficacy for two other anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder. In contrast to the treatment of depression, for which meta-analyses suggest an efficacy advantage relative to selective serotonin reuptake inhibitors (SSRIs), evidence of differential efficacy has not yet been established for any of the anxiety disorders. The overall tolerability profile of venlafaxine XR is generally comparable to that of the SSRIs, although there is greater incidence of noradrenergically mediated side effects (i.e., dry mouth and constipation), as well as a dose-dependent risk of treatment-emergent high blood pressure. Concerns about safety in overdose have also recently emerged. Despite these caveats, venlafaxine XR is an effective and generally well-tolerated option for treatment of anxiety disorders.

-----

Am J Geriatr Psychiatry. 2006 Mar;14(3):255-63.
A randomized, controlled trial of the effectiveness of cognitive-behavioral therapy and sertraline versus a waitlist control group for anxiety disorders in older adults.
Schuurmans J, Comijs H, Emmelkamp PM, Gundy CM, Weijnen I, van den Hout M, van Dyck R.
Department of Psychiatry and Institute for Research in Extramural Medicine, VU Medical Centre, Amsterdam, The Netherlands. j.schuurmans@psy.vu.nl

OBJECTIVE: This study is the first to investigate the relative effectiveness of cognitive-behavioral therapy (CBT) compared with a selective serotonin reuptake inhibitor (SSRI; sertraline) in a randomized, controlled trial on the treatment of anxiety disorders in older adults. METHOD: Eighty-four patients 60 years of age and over with a principal diagnosis of generalized anxiety disorder, panic disorder, agoraphobia, or social phobia were randomly assigned to one of three conditions: 15 sessions of CBT, pharmacologic treatment with an SSRI (sertraline; maximum dosage 150 mg), or a waitlist control group. Participants completed measures of primary outcome (anxiety) and coexistent worry and depressive symptoms at baseline, posttreatment, and at three-month follow up. RESULTS: Attrition rates were high in both treatment groups. Consequently, findings are based on a relatively small sample of completers (N = 52). Although both CBT and sertraline led to significant improvement in anxiety, worry, and depressive symptoms both at posttreatment and at three-month follow up, sertraline showed superior results on worry symptoms. Effect size estimates for CBT were in the small to medium range both at posttreatment (mean d = 0.42) and at three-month follow up (mean d = 0.35), whereas effect sizes for sertraline fell into the large range (posttreatment mean d = 0.94 and three-month follow up mean d = 1.02). The waitlist condition showed virtually no effects (posttreatment mean d = .03). CONCLUSIONS: Our findings strongly suggest that the pharmacologic treatment of late-life anxiety with SSRIs has not been given the proper attention in research to date.

-----

J Clin Psychopharmacol. 2006 Feb;26(1):45-9.
Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial.
Sepede G, De Berardis D, Gambi F, Campanella D, La Rovere R, D'Amico M, Cicconetti A, Penna L, Peca S, Carano A, Mancini E, Salerno RM, Ferro FM.
Department of Oncology and Neurosciences, Institute of Psychiatry, University G. D Annunzio of Chieti, Italy.

The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open-label study, 31 adult outpatients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5 mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed the trial period with a dropout rate of 16.1%. At week 12, 21 patients were responders (81.8%), and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia. Fifteen patients (57.7%) achieved remission. Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal symptoms were reported. Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD, but study limitations must be considered and placebo-controlled studies are needed.

-----

Br J Psychiatry. 2005 Oct;187:352-9.
Venlafaxine extended-release capsules in panic disorder: Flexible-dose, double-blind, placebo-controlled study.
Bradwejn J, Ahokas A, Stein DJ, Salinas E, Emilien G, Whitaker T.
University of Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, 1145 Carling Avenue, Ottawa, Ontario, Canada K1Z 7K4.

BACKGROUND: Venlafaxine extended-release (ER) has proven efficacy in the treatment of anxiety symptoms in major depression, generalised anxiety disorder and social anxiety disorder. AIMS: To evaluate the efficacy, safety and tolerability of venlafaxine ER in treating panic disorder. METHOD: Adult out-patients (n=361) with panic disorder were randomly assigned to receive venlafaxine ER (75-225 mg/day) or placebo for up to 10 weeks in a double-blind study. RESULTS: Venlafaxine ER was not associated with a greater proportion of patients free from full-symptom panic attacks at the final on-therapy evaluation, but was associated with lower mean panic attack frequency and a higher proportion free from limited-symptom panic attacks, higher response and remission rates, and improvements in anticipatory anxiety, fear and avoidance. Adverse events were comparable with those of the drug in depression and anxiety disorders. CONCLUSIONS: Venlafaxine ER seems to be effective and well tolerated in the short-term treatment of panic disorder.

-----

Behav Res Ther. 2005 Oct;43(10):1321-33. Epub 2004 Dec 13.
Treatment of panic disorder: live therapy vs. self-help via the Internet.
Carlbring P, Nilsson-Ihrfelt E, Waara J, Kollenstam C, Buhrman M, Kaldo V, Soderberg M, Ekselius L, Andersson G.
Department of Psychology, Uppsala University, Box 1225, 751 42 Uppsala, Sweden.

A randomized trial was conducted comparing 10 individual weekly sessions of cognitive behaviour therapy for panic disorder (PD) with or without agoraphobia with a 10-module self-help program on the Internet. After confirming the PD diagnosis with an in-person structured clinical interview (SCID) 49 participants were randomized. Overall, the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail can be equally effective as traditional individual cognitive behaviour therapy. Composite within-group effect sizes were high in both groups, while the between-group effect size was small (Cohen's d=16). One-year follow-up confirmed the results, with a within-group effect size of Cohen's d=0.80 for the Internet group and d=0.93 for the live group. The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs.

-----

J Affect Disord. 2005 Sep;88(1):27-45.
A meta-analysis of the efficacy of psycho- and pharmacotherapy in panic disorder with and without agoraphobia.
Mitte K.
University of Jena, Germany. mail@kristin-mitte.de

The efficacy of (cognitive) behavioural ((C)BT) and pharmacological therapy was investigated using meta-analytic techniques. After a comprehensive review of the literature, the results of 124 studies were included. (C)BT was more effective than a no-treatment control and a placebo control. No difference of efficacy was found when using cognitive elements compared to not using them for anxiety; for associated depressive symptoms, additional cognitive elements seems superior. Pharmacotherapy was more effective than a placebo control; there was no superiority of any drug class. Sample size was related to effect size in pharmacotherapy and publication bias was found. (C)BT was at least as effective as pharmacotherapy and depending on type of analysis even significantly more effective. There were no significant differences between (C)BT alone and a combination approach but characteristics of studies have to be considered.

-----

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.

-----

J Behav Ther Exp Psychiatry. 2005 Aug 25; [Epub ahead of print]
Efficacy of internet therapy for panic disorder.
Klein B, Richards JC, Austin DW.
University of Ballarat, Ballarat, Australia.

Fifty-five people with panic disorder (PD) were randomised to internet-based cognitive behavioural panic treatment (CBT) (with email contact), therapist-assisted CBT manual or information-only control (both with telephone contact). Both CBT treatments were more effective in reducing PD symptomatology, panic-related cognition, negative affect, and number of GP visits and improving physical health ratings. Internet treatment was more effective than CBT manual in reducing clinician-rated agoraphobia and number of GP visits at post-assessment. At follow-up, these effects were maintained for both CBT groups, with internet CBT better at improving physical health ratings and reducing GP visits. This study provides support for the efficacy of internet-based CBT.

-----

Behav Res Ther. 2005 Aug 4; [Epub ahead of print]
A pilot study of two-day cognitive-behavioral therapy for panic disorder.
Deacon B, Abramowitz J.
Department of Psychology, University of Wyoming, Dept. 3415, 1000 E. University Ave., Laramie, WY 82071, USA.

The present study investigated the short-term efficacy of brief, intensive cognitive-behavioral therapy (CBT) for panic disorder (PD). The treatment involved 9h of therapist contact over two consecutive days and was developed for the purpose of delivering CBT for PD to a largely rural patient population that must travel long distances to find a treatment provider. Ten patients who elected to participate in brief, intensive CBT instead of weekly CBT were recruited from routine clinical practice in a hospital-based anxiety disorders clinic. Patients were not excluded based on the presence of agoraphobia, diagnostic comorbidity, concurrent use of PRN benzodiazepine medications, or previous nonresponse to psychotherapy for PD. Assessments conducted at pre-treatment and 1-month follow-up revealed large, clinically significant reductions in PD symptoms, anxiety sensitivity, body vigilance, and anxiety and depressive symptoms. Most patients (60%) were panic-free after treatment and evidenced normative levels of symptomatology at follow-up. The present study suggests that brief, intensive treatment may be an effective means of delivering CBT for PD.

-----

Behav Res Ther. 2005 Jul 19; [Epub ahead of print]
One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remission.
Heldt E, Gus Manfro G, Kipper L, Blaya C, Isolan L, Otto MW.
Anxiety Disorders Program, Hospital de Clinicas de Porto Alegre, RS and Post-Graduate Program in Medical Sciences: Psychiatry, Universidade Federal do Rio Grande do Sul, Brazil.

Non-response to pharmacotherapy for panic disorder (PD) is a well-documented problem. However, little information exists to guide next-step strategies for these non-responders. In addition to pharmacologic augmentation strategies, several studies support the efficacy of cognitive-behavior therapy (CBT) for these patients, although data on long-term outcomes has been lacking. In this study, we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy. Sustained significant benefit was found for all dimensional outcome scores, and nearly two-thirds of the sample met remission criteria. This occurred with reductions in medication use over the follow-up period. Negative predictors of remission status included comorbid dysthymia, social phobia, and generalized anxiety disorder. These results provide additional evidence for the efficacy of CBT for medication non-responders with PD.

-----

Expert Rev Neurother. 2005 Jul;5(4):443-9.
Escitalopram in the treatment of generalized anxiety disorder.
Baldwin DS, Nair RV.
Division of Clinical Neurosciences, University Department of Mental Health, RSH Hospital, Graham Road, Southampton, SO14 0YG, UK. dsb1@soton.ac.uk

The selective serotonin reuptake inhibitor escitalopram is the active enantiomer of citalopram and has proven efficacy in the treatment of major depression, panic disorder and social phobia. Accumulating data indicate that it is also efficacious in the treatment of patients with generalized anxiety disorder. This drug profile summarizes the current evidence-base for the treatment of generalized anxiety disorder, describes the findings of a series of randomized placebo-controlled and comparator-controlled trials of escitalopram, examines the strengths and weaknesses of current treatment approaches and considers potential new therapies for the treatment of this common, chronic and impairing anxiety disorder. In summary, escitalopram is effective and well tolerated in both the short- and long-term treatment of generalized anxiety disorder, and has advantages over benzodiazepines and the selective serotonin reuptake inhibitor paroxetine.

-----

Nord J Psychiatry. 2005 Jun;59(3):198-204.
Cognitive-behavioural group treatment of panic disorder and agoraphobia in a psychiatric setting: A naturalistic study of effectiveness.
[No authors listed]

The purpose of the present study was to investigate the effectiveness of cognitive-behavioural group treatment of panic disorder and agoraphobia in a clinical setting. Fifty-three patients were offered treatment and assessed before, after and at follow-up 1(1/2)-2 years after treatment. The study included an informal waiting-list control group of 40 patients. The investigation group achieved better outcome on most analyses with 47.2% found to be panic-free after treatment compared with 12.5% in the control group. Treatment gains were durable with 66.7% without panic attacks at follow-up. Most patients, however, still had major psychological problems after treatment. The outcomes of cognitive-behavioural group treatment of panic disorder in this study were modest compared with most controlled studies, possibly due to an unselected patient group with a high degree of agoraphobia.

-----

Seishin Shinkeigaku Zasshi. 2005;107(7):641-66.
[Intensive Naikan therapy for generalized anxiety disorder and panic disorder: clinical outcomes and background]
[Article in Japanese]
Nukina S, Wang H, Kamei K, Kawahara R.
Division of Neuropsychiatry, Department of Multidisciplinary Internal Medicine, Tottori University.

OBJECT: Intensive Naikan therapy (INT) is used to treat irrational recognition, and to develop awareness of others and self-reflection. Several reports have also shown that INT is effective for treating anxiety disorders. The purpose of the present systematic study was to investigate the factors contributing to the efficacy and clinical outcomes of INT by assessing the background, psychological evolution, and treatment required after such therapy. METHOD: Twenty-eight anxiety disorder inpatients at Tottori University Hospital, 15 with general anxiety disorders (GAD) and 13 with panic disorders (PD), were treated with INT. Age, sex, duration of the present anxiety episode, and diagnosis were investigated. The Tokyo University Egogram (TEG), Yatabe-Guilford personality inventory (YG test) and Rosenzweig picture frustration (PF) study were conducted before and after INT to investigate psychological changes. The long-term efficacy of INT for PD and GAD was assessed with Global Assessment of Functioning (GAF). Whether the patients achieved awareness of others, awareness of egocentricity, feelings of love, and self reflection after INT were investigated. RESULTS: 1) All patients showed improved GAF; the average GAF score increased from 51 +/- 8 (before Naikan therapy) to 83.2 +/- 15 (after therapy). The clinical outcomes of INT were as follows: 17 patients showed extremely effective results (60.7%), 6 were effective (21.4%), 3 were slightly effective (10.7%), and 2 were unchanged (7.1%). Overall, 23 patients (82.1%) showed remarkable improvements as a result of INT (improved group) and 5 showed no remarkable improvements (not improved group). 2) The improved group included significantly more patients with obsessive tendencies or nervous personalities such as a premorbid personality. In addition, significantly more of the patients in this group underwent daily INT and improved more rapidly in the short-term. 3) According to the STAI (state trait anxiety inventory), both state-(S-anxiety), and trait-anxiety (T-anxiety) significantly decreased after INT. The PD group showed significantly reduced S and T-anxiety, but the GAD group only showed significantly reduced T-anxiety. The adult (A) and free child (FC) TEG scales significantly increased, and according to YG, nervousness (N) and depression (D) significantly decreased while general activity (G) and social extraversion (S) significantly increased. Furthermore, according to the PF study, extraggression (E -A) after INT significantly decreased and imaggression (I-A) significantly increased. In the improved group, significantly more patients became more aware of their partners (Naikan) and achieved an objective outlook, awareness of egocentricity, feelings of love and self-reflection after INT. CONCLUSIONS: Our results suggest that INT for PD and GAD is extremely effective, and a very important form of psychotherapy. Attainment of self-reflection caused psychological changes that motivated the patients to continue Naikan therapy daily. We consider this a key factor in maintaining the efficacy of INT.

-----

Prim Care Companion J Clin Psychiatry. 2005;7(3):100-5.
Medications for panic disorder and generalized anxiety disorder during pregnancy.
Rubinchik SM, Kablinger AS, Gardner JS.
Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque , and the Department of Psychiatry and the Psychopharmacology Research Clinic , Louisiana State University Health Sciences Center, Shreveport.

Objective: Approximately 30% of women experience some type of anxiety disorder during their lifetime. In addition, some evidence exists that anxiety disorders can affect pregnancy outcomes. This article reviews the literature on the course of generalized anxiety disorder (GAD) and panic disorder during pregnancy and the postpartum period and presents guidelines for management.Data Sources and Study Selection: An English language electronic search of relevant studies using PubMed (January 1, 1985-January 2004) was performed using the search terms anxiety and pregnancy, maternal mental illness, panic and pregnancy, psychotropic medications in pregnancy, and treatment options in pregnancy. Review articles and primary pharmacologic treatment articles were selected for discussion.Data Extraction and Synthesis: Despite the extensive use of psychotropic drugs such as antidepressants during pregnancy, there is a scarcity of information regarding the effect of such exposure on the developing fetus. Review articles and primary pharmacologic treatment trials were analyzed and incorporated into the review based on adequate methodology, completeness of data, and information on pregnancy outcome.Conclusion: It is important that physicians understand the course of these disorders during pregnancy and available treatments so they appropriately counsel women who are or intend to become pregnant. The goal of treatment during pregnancy and lactation is sufficient treatment for syndrome remission. To minimize the potential for neonatal withdrawal and maternal toxicity after delivery, vigilant monitoring of side effects is indicated. Also, if possible, nonpharmacologic treatment, such as cognitive-behavioral therapy, should be first-line treatment in pregnant women with GAD or panic disorder.

-----

Br J Psychiatry. 2005 Oct;187:352-9.
Venlafaxine extended-release capsules in panic disorder: Flexible-dose, double-blind, placebo-controlled study.
Bradwejn J, Ahokas A, Stein DJ, Salinas E, Emilien G, Whitaker T.
University of Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, 1145 Carling Avenue, Ottawa, Ontario, Canada K1Z 7K4.

BACKGROUND: Venlafaxine extended-release (ER) has proven efficacy in the treatment of anxiety symptoms in major depression, generalised anxiety disorder and social anxiety disorder. AIMS: To evaluate the efficacy, safety and tolerability of venlafaxine ER in treating panic disorder. METHOD: Adult out-patients (n=361) with panic disorder were randomly assigned to receive venlafaxine ER (75-225 mg/day) or placebo for up to 10 weeks in a double-blind study. RESULTS: Venlafaxine ER was not associated with a greater proportion of patients free from full-symptom panic attacks at the final on-therapy evaluation, but was associated with lower mean panic attack frequency and a higher proportion free from limited-symptom panic attacks, higher response and remission rates, and improvements in anticipatory anxiety, fear and avoidance. Adverse events were comparable with those of the drug in depression and anxiety disorders. CONCLUSIONS: Venlafaxine ER seems to be effective and well tolerated in the short-term treatment of panic disorder.

-----

Behav Res Ther. 2005 Oct;43(10):1321-33. Epub 2004 Dec 13.
Treatment of panic disorder: live therapy vs. self-help via the Internet.
Carlbring P, Nilsson-Ihrfelt E, Waara J, Kollenstam C, Buhrman M, Kaldo V, Soderberg M, Ekselius L, Andersson G.
Department of Psychology, Uppsala University, Box 1225, 751 42 Uppsala, Sweden.

A randomized trial was conducted comparing 10 individual weekly sessions of cognitive behaviour therapy for panic disorder (PD) with or without agoraphobia with a 10-module self-help program on the Internet. After confirming the PD diagnosis with an in-person structured clinical interview (SCID) 49 participants were randomized. Overall, the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail can be equally effective as traditional individual cognitive behaviour therapy. Composite within-group effect sizes were high in both groups, while the between-group effect size was small (Cohen's d=16). One-year follow-up confirmed the results, with a within-group effect size of Cohen's d=0.80 for the Internet group and d=0.93 for the live group. The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs.

-----

J Affect Disord. 2005 Sep;88(1):27-45.
A meta-analysis of the efficacy of psycho- and pharmacotherapy in panic disorder with and without agoraphobia.
Mitte K.
University of Jena, Germany. mail@kristin-mitte.de

The efficacy of (cognitive) behavioural ((C)BT) and pharmacological therapy was investigated using meta-analytic techniques. After a comprehensive review of the literature, the results of 124 studies were included. (C)BT was more effective than a no-treatment control and a placebo control. No difference of efficacy was found when using cognitive elements compared to not using them for anxiety; for associated depressive symptoms, additional cognitive elements seems superior. Pharmacotherapy was more effective than a placebo control; there was no superiority of any drug class. Sample size was related to effect size in pharmacotherapy and publication bias was found. (C)BT was at least as effective as pharmacotherapy and depending on type of analysis even significantly more effective. There were no significant differences between (C)BT alone and a combination approach but characteristics of studies have to be considered.

-----

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.

-----

J Behav Ther Exp Psychiatry. 2005 Aug 25; [Epub ahead of print]
Efficacy of internet therapy for panic disorder.
Klein B, Richards JC, Austin DW.
University of Ballarat, Ballarat, Australia.

Fifty-five people with panic disorder (PD) were randomised to internet-based cognitive behavioural panic treatment (CBT) (with email contact), therapist-assisted CBT manual or information-only control (both with telephone contact). Both CBT treatments were more effective in reducing PD symptomatology, panic-related cognition, negative affect, and number of GP visits and improving physical health ratings. Internet treatment was more effective than CBT manual in reducing clinician-rated agoraphobia and number of GP visits at post-assessment. At follow-up, these effects were maintained for both CBT groups, with internet CBT better at improving physical health ratings and reducing GP visits. This study provides support for the efficacy of internet-based CBT.

-----

Behav Res Ther. 2005 Aug 4; [Epub ahead of print]
A pilot study of two-day cognitive-behavioral therapy for panic disorder.
Deacon B, Abramowitz J.
Department of Psychology, University of Wyoming, Dept. 3415, 1000 E. University Ave., Laramie, WY 82071, USA.

The present study investigated the short-term efficacy of brief, intensive cognitive-behavioral therapy (CBT) for panic disorder (PD). The treatment involved 9h of therapist contact over two consecutive days and was developed for the purpose of delivering CBT for PD to a largely rural patient population that must travel long distances to find a treatment provider. Ten patients who elected to participate in brief, intensive CBT instead of weekly CBT were recruited from routine clinical practice in a hospital-based anxiety disorders clinic. Patients were not excluded based on the presence of agoraphobia, diagnostic comorbidity, concurrent use of PRN benzodiazepine medications, or previous nonresponse to psychotherapy for PD. Assessments conducted at pre-treatment and 1-month follow-up revealed large, clinically significant reductions in PD symptoms, anxiety sensitivity, body vigilance, and anxiety and depressive symptoms. Most patients (60%) were panic-free after treatment and evidenced normative levels of symptomatology at follow-up. The present study suggests that brief, intensive treatment may be an effective means of delivering CBT for PD.

-----

Behav Res Ther. 2005 Jul 19; [Epub ahead of print]
One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remission.
Heldt E, Gus Manfro G, Kipper L, Blaya C, Isolan L, Otto MW.
Anxiety Disorders Program, Hospital de Clinicas de Porto Alegre, RS and Post-Graduate Program in Medical Sciences: Psychiatry, Universidade Federal do Rio Grande do Sul, Brazil.

Non-response to pharmacotherapy for panic disorder (PD) is a well-documented problem. However, little information exists to guide next-step strategies for these non-responders. In addition to pharmacologic augmentation strategies, several studies support the efficacy of cognitive-behavior therapy (CBT) for these patients, although data on long-term outcomes has been lacking. In this study, we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy. Sustained significant benefit was found for all dimensional outcome scores, and nearly two-thirds of the sample met remission criteria. This occurred with reductions in medication use over the follow-up period. Negative predictors of remission status included comorbid dysthymia, social phobia, and generalized anxiety disorder. These results provide additional evidence for the efficacy of CBT for medication non-responders with PD.

-----

Expert Rev Neurother. 2005 Jul;5(4):443-9.
Escitalopram in the treatment of generalized anxiety disorder.
Baldwin DS, Nair RV.
Division of Clinical Neurosciences, University Department of Mental Health, RSH Hospital, Graham Road, Southampton, SO14 0YG, UK. dsb1@soton.ac.uk

The selective serotonin reuptake inhibitor escitalopram is the active enantiomer of citalopram and has proven efficacy in the treatment of major depression, panic disorder and social phobia. Accumulating data indicate that it is also efficacious in the treatment of patients with generalized anxiety disorder. This drug profile summarizes the current evidence-base for the treatment of generalized anxiety disorder, describes the findings of a series of randomized placebo-controlled and comparator-controlled trials of escitalopram, examines the strengths and weaknesses of current treatment approaches and considers potential new therapies for the treatment of this common, chronic and impairing anxiety disorder. In summary, escitalopram is effective and well tolerated in both the short- and long-term treatment of generalized anxiety disorder, and has advantages over benzodiazepines and the selective serotonin reuptake inhibitor paroxetine.

-----

Nord J Psychiatry. 2005 Jun;59(3):198-204.
Cognitive-behavioural group treatment of panic disorder and agoraphobia in a psychiatric setting: A naturalistic study of effectiveness.
[No authors listed]

The purpose of the present study was to investigate the effectiveness of cognitive-behavioural group treatment of panic disorder and agoraphobia in a clinical setting. Fifty-three patients were offered treatment and assessed before, after and at follow-up 1(1/2)-2 years after treatment. The study included an informal waiting-list control group of 40 patients. The investigation group achieved better outcome on most analyses with 47.2% found to be panic-free after treatment compared with 12.5% in the control group. Treatment gains were durable with 66.7% without panic attacks at follow-up. Most patients, however, still had major psychological problems after treatment. The outcomes of cognitive-behavioural group treatment of panic disorder in this study were modest compared with most controlled studies, possibly due to an unselected patient group with a high degree of agoraphobia.

-----

Seishin Shinkeigaku Zasshi. 2005;107(7):641-66.
[Intensive Naikan therapy for generalized anxiety disorder and panic disorder: clinical outcomes and background]
[Article in Japanese]
Nukina S, Wang H, Kamei K, Kawahara R.
Division of Neuropsychiatry, Department of Multidisciplinary Internal Medicine, Tottori University.

OBJECT: Intensive Naikan therapy (INT) is used to treat irrational recognition, and to develop awareness of others and self-reflection. Several reports have also shown that INT is effective for treating anxiety disorders. The purpose of the present systematic study was to investigate the factors contributing to the efficacy and clinical outcomes of INT by assessing the background, psychological evolution, and treatment required after such therapy. METHOD: Twenty-eight anxiety disorder inpatients at Tottori University Hospital, 15 with general anxiety disorders (GAD) and 13 with panic disorders (PD), were treated with INT. Age, sex, duration of the present anxiety episode, and diagnosis were investigated. The Tokyo University Egogram (TEG), Yatabe-Guilford personality inventory (YG test) and Rosenzweig picture frustration (PF) study were conducted before and after INT to investigate psychological changes. The long-term efficacy of INT for PD and GAD was assessed with Global Assessment of Functioning (GAF). Whether the patients achieved awareness of others, awareness of egocentricity, feelings of love, and self reflection after INT were investigated. RESULTS: 1) All patients showed improved GAF; the average GAF score increased from 51 +/- 8 (before Naikan therapy) to 83.2 +/- 15 (after therapy). The clinical outcomes of INT were as follows: 17 patients showed extremely effective results (60.7%), 6 were effective (21.4%), 3 were slightly effective (10.7%), and 2 were unchanged (7.1%). Overall, 23 patients (82.1%) showed remarkable improvements as a result of INT (improved group) and 5 showed no remarkable improvements (not improved group). 2) The improved group included significantly more patients with obsessive tendencies or nervous personalities such as a premorbid personality. In addition, significantly more of the patients in this group underwent daily INT and improved more rapidly in the short-term. 3) According to the STAI (state trait anxiety inventory), both state-(S-anxiety), and trait-anxiety (T-anxiety) significantly decreased after INT. The PD group showed significantly reduced S and T-anxiety, but the GAD group only showed significantly reduced T-anxiety. The adult (A) and free child (FC) TEG scales significantly increased, and according to YG, nervousness (N) and depression (D) significantly decreased while general activity (G) and social extraversion (S) significantly increased. Furthermore, according to the PF study, extraggression (E -A) after INT significantly decreased and imaggression (I-A) significantly increased. In the improved group, significantly more patients became more aware of their partners (Naikan) and achieved an objective outlook, awareness of egocentricity, feelings of love and self-reflection after INT. CONCLUSIONS: Our results suggest that INT for PD and GAD is extremely effective, and a very important form of psychotherapy. Attainment of self-reflection caused psychological changes that motivated the patients to continue Naikan therapy daily. We consider this a key factor in maintaining the efficacy of INT.

-----

Prim Care Companion J Clin Psychiatry. 2005;7(3):100-5.
Medications for panic disorder and generalized anxiety disorder during pregnancy.
Rubinchik SM, Kablinger AS, Gardner JS.
Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque , and the Department of Psychiatry and the Psychopharmacology Research Clinic , Louisiana State University Health Sciences Center, Shreveport.

Objective: Approximately 30% of women experience some type of anxiety disorder during their lifetime. In addition, some evidence exists that anxiety disorders can affect pregnancy outcomes. This article reviews the literature on the course of generalized anxiety disorder (GAD) and panic disorder during pregnancy and the postpartum period and presents guidelines for management.Data Sources and Study Selection: An English language electronic search of relevant studies using PubMed (January 1, 1985-January 2004) was performed using the search terms anxiety and pregnancy, maternal mental illness, panic and pregnancy, psychotropic medications in pregnancy, and treatment options in pregnancy. Review articles and primary pharmacologic treatment articles were selected for discussion.Data Extraction and Synthesis: Despite the extensive use of psychotropic drugs such as antidepressants during pregnancy, there is a scarcity of information regarding the effect of such exposure on the developing fetus. Review articles and primary pharmacologic treatment trials were analyzed and incorporated into the review based on adequate methodology, completeness of data, and information on pregnancy outcome.Conclusion: It is important that physicians understand the course of these disorders during pregnancy and available treatments so they appropriately counsel women who are or intend to become pregnant. The goal of treatment during pregnancy and lactation is sufficient treatment for syndrome remission. To minimize the potential for neonatal withdrawal and maternal toxicity after delivery, vigilant monitoring of side effects is indicated. Also, if possible, nonpharmacologic treatment, such as cognitive-behavioral therapy, should be first-line treatment in pregnant women with GAD or panic disorder.

-----

Behav Res Ther. 2005 Jul;43(7):959-70.
Impact of cognitive-behavioral therapy for panic disorder on comorbidity: a controlled investigation.
Tsao JC, Mystkowski JL, Zucker BG, Craske MG.
Department of Pediatrics, David Geffen School of Medicine, UCLA, 10940 Wilshire Blvd., Suite 1450, Los Angeles, CA 90024, USA. jtsao@mednet.ucla.edu

This study examined the effects of cognitive-behavioral therapy (CBT) for principal panic disorder with or without agoraphobia, on comorbidity in 30 individuals (16 female). To test the hypothesis that improvements in co-existing conditions were not due to spontaneous fluctuations across time, patients receiving immediate CBT were compared to those assigned to wait list (n = 11). Results indicated clinician-rated severity of comorbid specific phobia declined significantly following immediate CBT compared to no change after wait list. The number of patients without comorbidity of any severity increased after immediate CBT, with no such increase following wait list. However, the groups did not differ in the frequency of additional diagnoses or overall severity of comorbidity. In the total sample, results indicated reductions in comorbidity by 9-month follow-up, with marked declines in the severity of comorbid generalized anxiety disorder (GAD), social and specific phobia. Our findings suggest that targeted CBT for panic disorder has beneficial effects on comorbidity over the longer term and that some of its immediate effects exceed those due to the passage of time alone.

-----

Sleep Med Rev. 2005 Jun;9(3):173-84. Epub 2005 Apr 8.
Assessment and treatment of nocturnal panic attacks.
Craske MG, Tsao JC.
Department of Psychology, University of California, 405 Hilgard Ave., Los Angeles, CA 90095-1563, USA. craske@psych.ucla.edu

Nocturnal panic (NP), waking from sleep in a state of panic, is a common occurrence among patients with panic disorder, with 44-71% reporting at least one such attack. NP is a non-REM event that is distinct from sleep terrors, sleep apnea, nightmares or dream-induced arousals. This review outlines recent advances in the characterization of NP, as well as current approaches to the assessment and treatment of NP. In contrast to earlier work, more recent studies suggest that patients with NP do not differ from patients without NP on sleep architecture, sleep physiology, self-reported sleep quality and severity of panic disorder. However, more precise measurement of physiological precipitants and features is warranted. Assessment of NP focuses on ruling out other explanations for NP, with differential diagnosis based on interviews, sleep polysomnography and ambulatory recording of sleep. Psychological treatment (cognitive-behavioral therapy) targets misappraisals of anxiety sensations, hyperventilatory response, and conditioned reactions to internal, physical cues. Recent evidence supports the efficacy of this approach, however, controlled studies on pharmacological agents in the treatment of NP are lacking. Research is needed to examine the effects of combined cognitive-behavioral therapy and medications, compared to medication alone in the treatment of NP.

-----

Cogn Behav Ther. 2005;34(2):75-8.
Cognitive behaviour therapy for panic disorder: long-term follow-up.
Kenardy J, Robinson S, Dob R.
Centre of National Research on Disability and Rehabilitation Medicine, School of Medicine, University of Queensland, Herston, Australia. jkenardy@somc.uq.edu.au

This paper describes a long-term follow-up of patients with panic disorder who received cognitive behaviour therapy within a randomized controlled trial. Of 89 patients eligible for follow-up, 28 (31.5%) were reassessed 6-8 years after commencement of treatment in the trial. No differences were found between those who were followed up and those lost to follow-up on most baseline measures including measures of panic-related psychopathology, or depression. Outcomes at long-term follow-up were significantly better than baseline measures of panic, avoidance and depression. In this sub-sample the effect of cognitive behaviour therapy for panic disorder appears to maintain over the long-term.

-----

MMW Fortschr Med. 2005 May 17;147 Spec No 2:12, 14-6.
[Panic attacks and panic disorder: recognition and treatment]
[Article in German]
Boerner RJ.
Zentrum fur Diagnostik und Therapie von Angsterkrankungen, Christliches Krankenhaus e. V., Quakenbruck. psychiatrie@christliches-krankenhaus-ev.de

To recognize and treat panic attacks or a panic disorder are still an important function of the family doctor. For a one-time panic attack, specific counseling is normally sufficient. A panic disorder should be treated early with drugs and/or with psychotherapy and, in particular, with behavioral therapy. It is also recommended that a psychiatric specialist or a neurologist be consulted and to coordinate the differential diagnostics and therapeutic procedure with the specialist.

-----

Expert Rev Neurother. 2005 Mar;5(2):259-66.
Management of panic disorder.
Lader M.
Institute of Psychiatry, Denmark Hill, London, SE5 8AF, UK. m.lader@iop.kcl.ac.uk

Selective serotonin reuptake inhibitors are the first-line treatment for panic disorder. They are effective and well tolerated. Although tricyclic antidepressants are equally effective, they are less well tolerated than the selective serotonin reuptake inhibitors. Monoamine oxidase inhibitors can be efficacious but have a range of unwanted effects that preclude their use as first-line treatments. Benzodiazepines should be reserved for short-term use and for treatment-resistant patients who do not have a history of dependence and tolerance. Also, they can be combined with selective serotonin reuptake inhibitors in the first weeks of treatment to tide the patient over before the onset of the response. Cognitive behavioral therapy is the psychologic treatment of first choice. The methods of combining drug and nondrug treatments need careful and thorough exploration.

-----

J Clin Psychiatry. 2005;66 Suppl 4:23-7.
The pharmacotherapy of panic disorder.
Pollack MH.
Center for Anxiety and Traumatic Stress Related Disorders, Massachusetts General Hospital, Harvard Medical School, Boston, Mass, USA. mpollack@partners.org

Panic disorder is common and associated with significant morbidity and dysfunction. The pharmacologic treatment of panic disorder is aimed at reducing or eliminating panic attacks, avoidance behavior, anticipatory anxiety, and comorbid conditions--and substantially improving and normalizing overall function and quality of life. Antidepressants and benzodiazepines remain the current mainstays of pharmacotherapy for panic disorder, although other novel agents and strategies are becoming available and may add effective alternatives to the therapeutic armamentarium.

-----

Prim Care Companion J Clin Psychiatry. 2005;7(1):5-11.
The Role of High-Potency Benzodiazepines in the Treatment of Panic Disorder.
Susman J, Klee B.
Department of Family Medicine, University of Cincinnati, Cincinnati, Ohio ; and Pfizer Inc, New York, N.Y.

Medication plays a central role in the treatment of panic disorder, with the goal of eliminating panic attacks and restoring normal function (i.e., achieving full remission). Four drug classes have similar efficacy (tricyclic antidepressants, selective serotonin reuptake inhibitors [SSRIs], benzodiazepines, and monoamine oxidase inhibitors). Nonetheless, benzodiazepines remain the most prescribed medication for panic disorder in the United States. The high-potency benzodiaze-pines alprazolam (available as immediate- and extended-release tablets) and clonazepam (available as tablets and orally disintegrating wafers) are the only benzodiazepines approved by the U.S. Food and Drug Administration for the treatment of panic disorder. High-potency benzodiaze-pines, with their proven efficacy in panic disorder exerted through control of the central nervous system excitability by a selective and potent enhancement of inhibitory gamma-aminobutyric acid-mediated neurotransmission, are also a safe and well-tolerated option for potentiation of rapid treatment response when initiating treatment with SSRIs. Judicious use of high-potency benzodiazepines followed by a cautious taper and discontinuation may optimize the benefits and minimize any potential risk associated with this class of drugs.

-----

J Clin Psychiatry. 2005;66 Suppl 2:34-8.
Benzodiazepine use, cognitive impairment, and cognitive-behavioral therapy for anxiety disorders: issues in the treatment
of a patient in need.
Otto MW, Bruce SE, Deckersbach T.
Department of Psychology and Center for Anxiety and Related Disorders, Boston University, Boston, MA 02215, USA.

Cognitive-behavioral therapy (CBT) is effective in the treatment of anxiety disorders when used in conjunction with benzodiazepine pharmacotherapy and when used as a monotherapy. Patients using CBT alone have dropout rates similar to or lower than those patients undergoing other forms of therapy, including benzodiazepines. CBT also works well with patients who do not respond adequately to pharmacotherapy. Combined CBT and benzodiazepine treatment has additive effects when compared with benzodiazepine monotherapy; however, patients receiving combined therapy who subsequently discontinue benzodiazepine treatment experience a loss of efficacy compared with CBT and placebo, perhaps due to fear extinction being context dependent. To avoid this loss of efficacy, CBT may be administered alone or as a bridge between benzodiazepine use and discontinuation during a medication taper. The case report upon which this supplement is based questions the value of CBT for patients experiencing cognitive impairment due to an anxiety disorder, benzodiazepine medication, substance abuse, or a combination of these factors. This article addresses this concern and asserts that CBT is a valuable treatment option in these cases.

-----

Acta Psychiatr Scand. 2005 Apr;111(4):272-85.
A review of self-management interventions for panic disorders, phobias and obsessive-compulsive disorders.
Barlow JH, Ellard DR, Hainsworth JM, Jones FR, Fisher A.
Interdisciplinary Research Centre in Health, School of Health and Social Sciences, Coventry University, Coventry, UK.

Barlow JH, Ellard DR, Hainsworth JM, Jones FR, Fisher A. A review of self-management interventions for panic disorders, phobias and obsessive-compulsive disorders. Acta Psychiatr Scand 2005: 1-14. (c) Blackwell Munksgaard 2005.Objective: To review current evidence for the clinical and cost-effectiveness of self-management interventions for panic disorder, phobias and obsessive-compulsive disorder (OCD). Method: Papers were identified through computerized searches of databases for the years between 1995 and 2003, manual searches and personal contacts. Only randomized-controlled trials were reviewed. Results: Ten studies were identified (one OCD, five panic disorder, four phobias). Effective self-management interventions included cognitive-behavioural therapy (CBT) and exposure to the trigger stimuli for phobias and panic disorders. All involved homework. There was evidence of effectiveness in terms of improved symptoms and psychological wellbeing when compared with standard care, waiting list or relaxation. Brief interventions and computer-based interventions were effective for most participants. In terms of quality, studies were mainly based on small samples, lacked long-term follow-up, and failed to address cost-effectiveness. Conclusion: Despite the limitations of reviewed studies, there appears to be sufficient evidence to warrant greater exploration of self-management in these disorders.

-----

Depress Anxiety. 2005 Mar 22; [Epub ahead of print]
Potential effectiveness and safety of olanzapine in refractory panic disorder.
Hollifield M, Thompson PM, Ruiz JE, Uhlenhuth EH.
University of New Mexico School of Medicine, Albuquerque, New Mexico.

Panic disorder is a common and disabling psychiatric disorder. Despite treatment advances, refractory panic disorder requires novel interventions. One such pharmacologic intervention with theoretical and case study support includes olanzapine, a thienobenzodiazepine medication currently approved for schizophrenia in the United States. Ten people with refractory DSM-IV diagnosed panic disorder completed an 8-week, open-label, flexible-dose clinical trial. Baseline, in-treatment, and end-of-treatment data for panic attacks, anticipatory anxiety, phobic avoidance, and impairment were collected. Data were analyzed using SPSS software. Refractory panic disorder patients required a wide dose range averaging 12.3 mg/day of olanzapine to significantly improve or ablate panic attacks. On the average, number of attacks decreased from 6.1/week at baseline to 1.1/week at the end of treatment, and anticipatory anxiety from 32% of the day to 8% of the day. At treatment end, 5 of 10 participants (50%) were panic free, 4 (40%) had one attack in the previous week, 1 (10%) had seven attacks in the previous week, and 6 of 10 participants (60%) were anticipatory anxiety free. There were also statistically and clinically significant improvements in impairment over the course of the trial. There were no significant changes in vital signs, emergent side effects, or average weight, although 6 of 10 people did gain weight. Olanzapine is potentially effective and safe in panic disorder. Due to study limitations, further clinical trials are needed to demonstrate effectiveness. Depression and Anxiety 00:000-000, 2005. (c) 2005 Wiley-Liss, Inc.

-----

Arch Gen Psychiatry. 2005 Mar;62(3):290-8.
A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder.
Roy-Byrne PP, Craske MG, Stein MB, Sullivan G, Bystritsky A, Katon W, Golinelli D, Sherbourne CD.
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine at Harborview Medical Center, Seattle, USA.

BACKGROUND: Panic disorder is a prevalent, often disabling condition among patients in the primary care setting. Although numerous studies have assessed the effectiveness of treatments for depression in primary care, few such studies have been conducted for panic disorder. OBJECTIVE: To implement and test the effectiveness of a combined pharmacotherapy and cognitive-behavioral intervention for panic disorder tailored to the primary care setting. DESIGN: Randomized, controlled study comparing intervention to treatment as usual. SETTING: Six primary care clinics associated with 3 university medical schools, serving an ethnically and socioeconomically diverse patient population. PARTICIPANTS: Two hundred thirty-two primary care patients meeting DSM-IV criteria for panic disorder. Comorbid mental and physical disorders were permitted, provided these did not contraindicate the treatment to be provided and were not acutely life threatening. INTERVENTION: Patients were randomized to receive either treatment as usual or an intervention consisting of a combination of up to 6 sessions (across 12 weeks) of cognitive-behavioral therapy (CBT) modified for the primary care setting, with up to 6 follow-up telephone contacts during the next 9 months, and algorithm-based pharmacotherapy provided by the primary care physician with guidance from a psychiatrist. Behavioral health specialists, the majority inexperienced in CBT for panic disorder, were trained to deliver the CBT and coordinated overall care, including pharmacotherapy. MAIN OUTCOMES MEASURES: Proportion of subjects remitted (no panic attacks in the past month, minimal anticipatory anxiety, and agoraphobia subscale score <10 on Fear Questionnaire) and responding (Anxiety Sensitivity Index score <20) and change over time in World Health Organization Disability Scale and short form 12 scores. RESULTS: The combined cognitive-behavioral and pharmacotherapeutic intervention resulted in sustained and gradually increasing improvement relative to treatment as usual, with significantly higher rates at all points of both the proportion of subjects remitted (3 months, 20% vs 12%; 12 months, 29% vs 16%) and responding (3 months, 46% vs 27%; 12 months, 63% vs 38%) and significantly greater improvements in World Health Organization Disability Scale (all points) and short form 12 mental health functioning (3 and 6 months) scores. These effects were obtained in spite of similar rates of delivery of guideline-concordant pharmacotherapy to the 2 groups. CONCLUSION: Delivery of evidence-based CBT and medication using the collaborative care model and a CBT-naive, midlevel behavioral health specialist is feasible and significantly more effective than usual care for primary care panic disorder.

-----

CNS Spectr. 2005 Mar;10(3):176-9.
Ziprasidone as an augmenting agent in the treatment of anxiety-spectrum disorders.
Crane DL.
Mental Illness Prevention Center, New York University, New York, NY, USA.

Anxiety disorders are currently one of the most common health concerns in the United States. Overall, they are the single largest cost to the healthcare system. They are also underdiagnosed and undertreated. Selective serotonin reuptake inhibitors and benzodiazepines appear to be the most common pharmacologic treatment approaches. Unfortunately, not all patients respond to these treatments. Many augmentation strategies have been tried in the past with varying levels of success or safety. This article describes a safe and highly effective augmentation technique in patients suffering from some of the most serious and debilitating forms of anxiety disorders, namely obsessive-compulsive disorder and panic disorder.

-----

Am Fam Physician. 2005 Feb 15;71(4):733-9.
Treatment of panic disorder.
Ham P, Waters DB, Oliver MN.
Department of Family Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA. ph2t@virginia.edu

Panic disorder with or without agoraphobia occurs commonly in patients in primary care settings. This article assesses multiple evidence-based reviews of effective treatments for panic disorder. Antidepressant medications successfully reduce the severity of panic symptoms and eliminate panic attacks. Selective serotonin reuptake inhibitors and tricyclic antidepressants are equally effective in the treatment of panic disorder. The choice of medication is based on side effect profiles and patient preferences. Strong evidence supports the effectiveness of cognitive behavior therapy in treating panic disorder. Family physicians who are not trained in cognitive behavior therapy may refer patients with panic disorder to therapists with such training. Cognitive behavior therapy can be used alone or in combination with antidepressants to treat patients with panic disorder. Benzodiazepines are effective in treating panic disorder symptoms, but they are less effective than antidepressants and cognitive behavior therapy.

-----

Pharmacopsychiatry. 2005 Jan;38(1):24-9.
Randomized, double-blind study of SR142801 (Osanetant). A novel neurokinin-3 (NK3) receptor antagonist in panic disorder with pre- and posttreatment cholecystokinin tetrapeptide (CCK-4) challenges.
Kronenberg G, Berger P, Tauber RF, Bandelow B, Henkel V, Heuser I.
Psychiatric Department, Charite-CBF, Free University of Berlin, Germany.

OBJECTIVE: The present study was designed to examine the efficacy and tolerability of the non-peptide neurokinin-3 (NK3) receptor antagonist SR142801 in outpatients suffering from panic disorder. METHODS: In a pilot study, 52 patients who were responders to a cholecystokinin tetrapeptide (CCK-4) challenge were randomized to four weeks of treatment with SR142801 (n = 36) or placebo (n = 16). Panic symptoms were assessed on weekly visits and a second CCK-4 challenge was performed at the end of the double-blind placebo controlled treatment period. Tolerability of SR142801 was generally good. RESULTS: The proportion of patients who had at least one adverse event (AE) in the SR142801 group and the placebo group was similar (58.3 and 50 %, respectively). Independent of treatment group, patients' overall panic symptomatology was substantially improved at the end of the treatment. CONCLUSION: With regard to efficacy of outcome, the compound was not significantly different from placebo. However, post-CCK-4 plasma prolactin concentrations showed a significant difference between placebo and SR142801.

-----

J Clin Psychiatry. 2005 Jan;66(1):34-40.
Efficacy and tolerability of controlled-release paroxetine in the treatment of panic disorder.
Sheehan DV, Burnham DB, Iyengar MK, Perera P; Paxil CR Panic Disorder Study Group.
Institute for Research in Psychiatry, Department of Psychiatry, University of South Florida, Tampa, FL 33613-4788, USA. dsheehan@hsc.usf.edu

OBJECTIVE: To assess the efficacy and tolerability of controlled-release paroxetine (paroxetine CR) in the treatment of adults with panic disorder. METHOD: Paroxetine CR (25-75 mg/day; N = 444) was compared with placebo (N = 445) in patients with DSM-IV panic disorder with or without agoraphobia in 3 identical, double-blind, placebo-controlled, 10-week clinical trials that were pooled for analysis. RESULTS: Paroxetine CR was statistically superior to placebo in the primary outcome measure, percentage of patients who were free of panic attacks in the 2 weeks prior to endpoint. Of the total population that completed or prematurely terminated treatment, 63% and 53% of paroxetine CR-and placebo-treated patients, respectively, were panic-free during the final 2 weeks (p < .005; odds ratio [OR] = 1.63; 95% CI = 1.21 to 2.19). For week 10 completers (72% of total), 73% and 60% of paroxetine CR- and placebo-treated patients, respectively, were panic-free at week 10 (p < .005; OR = 2.11; 95% CI = 1.45 to 3.07). Paroxetine CR was also statistically superior to placebo on the global improvement and severity items of the Clinical Global Impressions scale and in reducing anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety total score and total fear and avoidance on the Marks-Sheehan Phobia Scale. Adverse events leading to study withdrawal were minimal and occurred in 11% of the paroxetine CR group and 6% of the placebo group. Most of the treatment-emergent adverse events were rated as mild to moderate in severity and occurred early in the study. There were no unexpected adverse events, and serious adverse events were uncommon (10 [2.3%] of the 444 patients treated with paroxetine CR vs. 8 [1.8%] of the 445 patients treated with placebo). CONCLUSION: Paroxetine CR is an effective and well-tolerated treatment for panic disorder. Paroxetine CR is associated with low rates of treatment-emergent anxiety as well as low dropout rates from adverse events.

-----

Int Clin Psychopharmacol. 2005 Jan;20(1):9-11.
Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients.
Worthington JJ 3rd, Kinrys G, Wygant LE, Pollack MH.
aCenter for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston, Massachusetts cDepartment of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA bAnxiety Disorders Research Program, Cambridge Health Alliance, Cambridge, Massachusetts.

More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve. We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic, aripiprazole. We report on patients with depression and anxiety disorders, including panic disorder, generalized anxiety disorder, social anxiety and post-traumatic stress disorder, who had an incomplete response to a variety of selective serotonin reuptake inhibitors (SSRIs) and who received augmentation with aripiprazole. The primary outcome measure was the Clinical Global Impression of Improvement (CGI-I). In the intent-to-treat analysis, the mean+/-SD CGI-S was 3.8+/-1.3 at endpoint. Fifty-nine percent of subjects received CGI-I ratings of 1 or 2, 'much improved' or 'very much improved,' in terms of their depression and anxiety symptoms at the end of 12 weeks. Several patients showed an early (weeks 1-5), as well as sustained, response to augmentation with doses of aripiprazole between 15 and 30 mg/day. The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment. Because this is a retrospective case review, further prospective studies are required to confirm these findings.

-----

J Clin Psychiatry. 2004;65 Suppl 14:22-6.
Overview of panic and social anxiety disorders.
Westenberg HG, Liebowitz MR.
>From the Department of Psychiatry, University Medical Centre, Utrecht, the Netherlands (Dr. Westenberg), and the Anxiety Disorders Program, New York State Psychiatric Institute, New York, N.Y. (Dr. Liebowitz).

Panic disorder and social anxiety disorder are often-overlooked but debilitating disorders that share some common symptoms and treatments. Patients with panic disorder experience unexpected panic attacks and then worry about having more attacks. Those with social anxiety disorder fear doing or saying something embarrassing in social situations. The prevalence of these conditions is about 3% for panic disorder and 13% for social anxiety disorder in the United States and is higher in women than in men. Both disorders are thought to have a familial link and to be related to dysregulation of neurotransmitter systems. Panic and social anxiety disorders are often comorbid with other psychiatric disorders. Medication treatment and/or cognitive-behavioral therapy might need to be continued over the long term to prevent relapse.

-----

MMW Fortschr Med. 2004 Oct 14;146(42):45-6, 48.
[Diagnosis and treatment of panic disorder]
[Article in German]
Rupprecht R, Moller HJ.
Klinik fur Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universitat Munchen. Rainer.Rupprecht@psy.med.uni-muenchen.de

Panic disorder is defined as, recurrent, unexpected panic attacks. Panic attack means a period of intensive fear or discomfort, accompanied by a range of physical or psychological symptoms. Subsequently, anticipatory anxiety and avoidance behavior often develop. Panic disorder may or may not be accompanied by agoraphobia. Panic disorder can be treated both by psychotherapeutic and pharmacological measures. An ideal approach is combination therapy in the sense of a multimodal concept; with regard to cognitive behavioral therapy in particular, its effectiveness in the treatment of panic disorder is well documented. For pharmacotherapy, antidepressive agents, in particular selective serotonin reuptake inhibitors, are the drugs of first choice. Benzodiazepines should be given for only a few weeks until the antipanic effect of the antidepressants kicks in. With appropriate treatment, the prognosis is favorable.

-----

Med J Aust. 2004 Oct 4;181(7 Suppl):S29-46.
Effectiveness of complementary and self-help treatments for anxiety disorders.
Jorm AF, Christensen H, Griffiths KM, Parslow RA, Rodgers B, Blewitt KA.
Centre for Mental Health Research, Australian National University, Building 63, Eggleston Road, Acton, ACT 0200, Australia. anthony.jorm@anu.edu.au.

OBJECTIVES: To review the evidence for the effectiveness of complementary and self-help treatments for anxiety disorders. DATA SOURCES: Systematic literature search using PubMed, PsycLit, and the Cochrane Library. DATA SYNTHESIS: 108 treatments were identified and grouped under the categories of medicines and homoeopathic remedies, physical treatments, lifestyle, and dietary changes. We give a description of the 34 treatments (for which evidence was found in the literature searched), the rationale behind the treatments, a review of studies on effectiveness, and the level of evidence for the effectiveness studies. CONCLUSIONS: The treatments with the best evidence of effectiveness are kava (for generalised anxiety), exercise (for generalised anxiety), relaxation training (for generalised anxiety, panic disorder, dental phobia and test anxiety) and bibliotherapy (for specific phobias). There is more limited evidence to support the effectiveness of acupuncture, music, autogenic training and meditation for generalised anxiety; for inositol in the treatment of panic disorder and obsessive-compulsive disorder; and for alcohol avoidance by people with alcohol-use disorders to reduce a range of anxiety disorders.

-----

Drugs. 2004;64(19):2199-220.
Antiepileptic drugs in the treatment of anxiety disorders: role in therapy.
Van Ameringen M, Mancini C, Pipe B, Bennett M.
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada. vanamer@mcmaster.ca

Pharmacotherapy for anxiety disorders is an active area of research. A variety of drug groups have been shown to be effective in treating many of the anxiety disorders, with selective serotonin reuptake inhibitors (SSRIs) being considered first-line agents for virtually all anxiety disorders. There is a clinical need for alternative drug treatments, as many patients do not achieve a complete response and experience significant adverse effects. The successful use of antiepileptic drugs in mood disorders has led clinicians and researchers to investigate their potential efficacy in other psychiatric disorders, particularly in anxiety disorders. There have been a number of investigations conducted in the form of case reports, case series and open-label trials, suggesting the potential usefulness of antiepileptic drug treatment in a variety of anxiety disorders. More reliable evidence for the use of antiepileptic drugs in anxiety disorders can be gleaned from recent placebo-controlled trials. Thus far, the strongest placebo-controlled evidence has demonstrated the efficacy of pregabalin in treating social phobia and generalised anxiety disorder, while smaller or less robust controlled trials have suggested the potential efficacy of gabapentin in social phobia, lamotrigine in post-traumatic stress disorder, and valproic acid in panic disorder. Antiepileptic drugs may have a place in the treatment of anxiety disorders; however, further investigation is warranted to determine in what circumstances they should be used as monotherapy or as augmenting agents in individuals who are partially or non-responsive to conventional therapy.

-----

CNS Spectr. 2004 Oct;9(10):725-39.
Treatment-resistant panic disorder.
Bandelow B, Ruther E.
Department of Psychiatry and Psychotherapy, University of Gottingen, Germany. bbandel@gwdg.de

A substantial number of patients with panic disorder and agoraphobia may remain symptomatic after standard treatment (including selective serotonin reuptake inhibitors, tricyclic antidepressants, benzodiazepines, or irreversible monamine oxidase inhibitors). In this review, recommendations for the treatment of patients with panic disorder and agoraphobia who do not respond to these drugs are provided. Nonresponse to drug treatment could be defined as a failure to achieve a 50% reduction on a standard rating scale after a minimum of 6 weeks of treatment in adequate dose. When initial treatments have failed, the medication should be changed to other standard treatments. In further attempts at treatment, drugs should be used that have shown promising results in preliminary studies, such as venlafaxine. Combination treatments may be used, such as the combination of an selective serotonin reuptake inhibitor and a benzodiazepine. Psychological treatments such as cognitive-behavioral therapy have to be considered in all patients, regardless whether they are nonresponders or not. According to existing studies, a combination of pharmacologic treatment with cognitive-behavioral therapy can be recommended.

-----

Behav Res Ther. 2004 Oct;42(10):1105-27.
Cognitive behavior therapy vs exposure in vivo in the treatment of panic disorder with agrophobia.
Ost LG, Thulin U, Ramnero J.
Department of Psychology, Stockholm University, S-106 91 Stockholm, Sweden.

Seventy-three psychiatric outpatients with DSM-IV diagnosis of panic disorder with agoraphobia were assessed with a battery of independent assessor, self-observation, self-report and behavioral measures before and after therapy, and at a 1-yr follow-up. They were randomly assigned to Exposure in vivo (E; [Formula: see text] ), Cognitive Behavior Therapy (CBT; [Formula: see text] ), or a Wait-list control (WLC; [Formula: see text] ) and received 12-16 individual therapy sessions, once weekly. The treatments yielded significant improvements, both on panic/agoraphobia measures and on measures of general anxiety, depression, social adjustment and quality of life, which were maintained at follow-up. However, there were no significant differences between E and CBT. The three criteria of clinically significant improvement were achieved by 67% of the E-patients and 79% of the CBT-patients at post-treatment, and 74% and 76%, respectively, at follow-up. The conclusion that can be drawn is that adding cognitive therapy to exposure did not yield significantly better results than for exposure alone.

-----

J Psychiatr Res. 2004 Sep-Oct;38(5):491-5.
Changes in anxiety sensitivity with pharmacotherapy for panic disorder.
Simon NM, Otto MW, Smits JA, Nicolaou DC, Reese HE, Pollack MH.
Anxiety Disorders Program, Massachusetts General Hospital and Harvard Medical School, WACC-812, 15 Parkman Street, Boston, MA 02114, USA.

Fear of anxiety symptoms (anxiety sensitivity) has been implicated in the etiology and maintenance of panic disorder, and has been shown to improve with cognitive-behavioral treatment. The impact of pharmacotherapy on anxiety sensitivity is less clear. We administered the Anxiety Sensitivity Index (ASI) during a 12-week randomized controlled trial investigating the relative efficacy of paroxetine, paroxetine plus sustained clonazepam, and paroxetine plus brief clonazepam for patients with panic disorder. We found a mean reduction in ASI scores of 9.6 points, which correlated with symptomatic improvement, and did not differ significantly between groups. Our data provides further evidence that pharmacotherapy leads to significant acute reductions in fears of anxiety symptoms in patients with panic disorder, albeit at levels that may be somewhat less than the changes associated with CBT. Implications of these findings are discussed relative to optimizing pharmacologic treatment of panic disorder.

-----

Pharmacopsychiatry. 2004 Sep;37(5):206-10.
Comparison of the treatment with paroxetine and reboxetine in panic disorder: a randomized, single-blind study.
Bertani A, Perna G, Migliarese G, Di Pasquale D, Cucchi M, Caldirola D, Bellodi L.
Anxiety Disorder Clinical and Research Unit, Department of Neuropsychiatric Sciences, Vita-Salute University, Istituto Scientifico Ospedale San Raffaele, Milan, Italy.

INTRODUCTION:: Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder (PD). However preliminary studies suggested that reboxetine might be effective in the treatment of PD. We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD. METHODS: Sixty-eight patients with PD were assigned to treatment groups in a single-blind, randomized design. Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale (PASS), the Sheehan Disability Scale (SDS) and the Fear Questionnaire (FQ). Side effects were also recorded. RESULTS: Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one. Vice versa we did not find any significant differences for other outcome measures. Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group. CONCLUSIONS: The results showed a greater effect of paroxetine on panic attacks than reboxetine, while no differences for anticipatory anxiety and avoidance were found, suggesting a different role of noradrenaline and serotonin in the treatment of PD.

-----

Am J Psychiatry. 2004 Aug;161(8):1485-7.
Differential response to placebo among patients with social phobia, panic disorder, and obsessive-compulsive disorder.
Huppert JD, Schultz LT, Foa EB, Barlow DH, Davidson JR, Gorman JM, Shear MK, Simpson HB, Woods SW.
Center for Treatment and Study of Anxiety, University of Pennsylvania School of Medicine, 6th Floor, 3535 Market St., Philadelphia, PA 19104, USA. huppert@mail.med.upenn.edu

OBJECTIVE: Placebo effects in treatment of three anxiety disorders were compared. METHOD: Treatment response and patients' treatment expectancy were examined by using data from 70 patients with obsessive-compulsive disorder, social phobia, or panic disorder who received placebo in three randomized, controlled trials comparing cognitive behavior therapy, medication, and their combination to placebo. RESULTS: Patients with obsessive-compulsive disorder were less likely to respond to placebo than patients with generalized social phobia or panic disorder. Differential expectancy did not account for these findings. CONCLUSIONS: Further examination of the placebo effect across the anxiety disorders may elucidate maintenance mechanisms of these disorders and have implications for development of more effective treatments.

-----

Stud Health Technol Inform. 2004;99:73-90.
The use of VR in the treatment of panic disorders and agoraphobia.
Botella C, Villa H, Garcia Palacios A, Quero S, Banos RM, Alcaniz M.
Department of Clinical Psychology, Universitat Jaume I, Castellon, Spain.

Panic disorder with agoraphobia (PDA) is considered an important public health problem. The efficacy of cognitive-behavioral therapy (CBT) for PDA has been widely demonstrated. The American National Institute of Health recommended Cognitive-Behavioral programs as the treatment of choice for this disorder. This institution also recommended that researchers develop treatments whose mode of delivery increases the availability of these programs. Virtual Reality based treatments can help to achieve this goal. VR has several advantages compared with conventional techniques. One of the essential components to treat these disorders is exposure. In VR the therapist can control the feared situations at will and with a high degree of safety for the patient, as it is easier to grade the feared situations. Another advantage is that VR is more confidential because treatment takes place in the therapist's office. It is also less time consuming as it takes place in the therapist's office. Considering the wide number of situations and activities that agoraphobic patients use to avoid, VR can save time and money significantly. Another advantage in treating PDA using VR is the possibility of doing VR interoceptive. VR could be a more natural setting for interoceptive exposure than the consultation room because we can elicit bodily sensations while the patient is immerse in VR agoraphobic situations. Finally, we think that VR exposure can be a useful intermediate step for those patients who refuse in vivo exposure because the idea of facing the real agoraphobic situations is too aversive for them. In this chapter we offer the work done by our research team at the VEPSY-UPDATED project. We describe the VR program we have developed for the treatment of PDA and we summarize the efficacy and effectiveness data of a study where we compare a cognitive-behavioral program including VR for the exposure component with a standard cognitive-behavioral program including in vivo exposure and with a waiting list control condition. Our findings support the efficacy and effectiveness of VR for the treatment of PDA.

-----

Expert Opin Pharmacother. 2004 Jul;5(7):1599-611.
Alprazolam extended-release in panic disorder.
Rickels K.
University of Pennsylvania, Department of Psychiatry, University of Pennsylvania Medical Center, PA 19104-3309, USA. krickels@mail.med.upenn.edu

Alprazolam-XR is an extended-release formulation of alprazolam designed to deliver sustained therapeutic concentrations for 24 h after once-daily dosing. Plasma concentrations gradually decline as the time for the next dose approaches, but still remain above therapeutic minimum levels. The anti-panic efficacy of alprazolam-XR appears to be comparable to the original formulation of alprazolam. The main advantage of the new extended-release formulation appears to be its greater tolerability and safety. The speed with which high-potency benzodiazepines are absorbed, and rise to peak concentrations is correlated with both abuse potential and with the incidence and severity of common adverse events, such as sedation and cognitive and psychomotor impairment. Alprazolam-XR does not exhibit the sudden increases in plasma concentration characteristic of the original formulation of alprazolam. This pharmacokinetic difference appears to translate into a reduced liability of abuse and a reduced incidence of sedation and cognitive and psychomotor impairment during acute therapy. This would appear to give alprazolam-XR a more favourable benefit:risk profile than the original formulation of alprazolam. In addition, the once-daily dosing (as opposed to three or four times per day) reduces clock-watching, increases compliance and it eliminates the penalty of breakthrough anxiety and panic that many patients experience if they inadvertently miss a dose. It should be noted that long-term therapy with alprazolam-XR carries the same risk of dependence and withdrawal during discontinuation as the original formulation of alprazolam.

-----

BMC Psychiatry. 2004 Jun 11;4(1):16.
Three year naturalistic outcome study of panic disorder patients treated with paroxetine.
Dannon PN, Iancu I, Cohen A, Lowengrub K, Grunhaus L, Kotler M.
The Rehovot Community Mental Health Care & Rehabilitation Center affiliated to Tel Aviv University, 76449, Israel. pinhasd@post.tau.ac.il

BACKGROUND: This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment, 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia, 3) To observe paroxetine's tolerability over a 24 month period. METHODS: 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner. RESULTS: Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase. CONCLUSIONS: The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment.

-----

Nihon Shinkei Seishin Yakurigaku Zasshi. 2004 Jun;24(3):133-6.
[Recent trends in pharmacotherapy for anxiety disorders]
[Article in Japanese]
Tajima O.
Department of Mental Health, Kyorin University, School of Health Sciences, Miyashita-cho, Hachioji, Tokyo, 192-8508 Japan.

Since the introduction of SSRIs, pharmacotherapy for anxiety disorders has significantly changed. Although the SSRIs are considered to be a first-line treatment for the most of anxiety disorders benzodiazepines are still widely used in clinical practice despite the risk of dependence and strong recommendation for their use as a second-line. The SSRIs only replaced tricyclic antidepressants and the MAO inhibitors especially in the treatment of panic disorder, obsessive-compulsive disorder and social phobia. Combination of the SSRIs and the benzodiazepines is widely used. Recently it has been suggested that the combination of SSRI and benzodiazepine is rational, because each drug has a different mechanism of action, the benzodiazepines enhancing GABAergic transmission, and the SSRIs stimulating the 5-HT1A receptor that may inhibit the postsynaptic neuronal excitability in the amygdala and the prefrontal cortex that comprise the brain circuit of fear and anxiety. Recent imaging studies suggested the hyperactivity of the amygdala in the patients with generalized social anxiety disorder and successful treatment with cognitive behavioral therapy or SSRI might significantly reduce the hyperactivity of the amygdala. It was suggested that the rational combination of SSRIs and benzodiazepines seems to be an effective and practical way of treatment for most anxiety disorders.

-----

J Am Dent Assoc. 2004 Jun;135(6):771-8; quiz 796-7.
Panic disorder: psychopathology, medical management and dental implications.
Friedlander AH, Marder SR, Sung EC, Child JS.
VA Greater Los Angeles Healthcare System, Calif 90073, USA. arthur.friedlander@med.va.gov

BACKGROUND: This article reviews the clinical features, epidemiology, pathophysiology, dental findings, and dental and medical management of the care of patients with panic disorder, or PD. TYPES OF STUDIES REVIEWED: The authors conducted a MEDLINE search for the period 1998 through 2003, using the key term "panic disorder" to define the pathophysiology of the disorder, its epidemiology and dental implications. The articles they selected for further review included those published in peer-reviewed journals. RESULTS: PD is a common and debilitating psychiatric disease in which a person experiences sudden and unpredictable panic attacks, or PAs, with symptoms of overwhelming anxiety, chest pain, palpitations and shortness of breath. Persistent concern about having another attack and worry that it may indicate a heart attack or "going crazy" impairs the person's social, family and working lives. Frequently accompanying the disorder is agoraphobia, depression and mitral valve prolapse, or MVP. CLINICAL IMPLICATIONS: In patients with PD, the prevalence of dental disease may be extensive because of the xerostomic effects of psychiatric medications used to treat it. Dental treatment consists of preventive dental education and prescribing saliva substitutes and anticaries agents. Precautions must be taken when prescribing or administering analgesics, antibiotics or sedative agents that may have an adverse interaction with the psychiatric medications. Because there is a connection between PAs and MVP, the dentist needs to consult with the patient's physician to determine the presence of MVP and whether there is associated mitral valve regurgitation. Patients with MVP and accompanying mitral valve regurgitation require prophylactic antibiotics when undergoing dental procedures known to cause a bacteremia and heightened risk of endocarditis.

-----

J Psychiatr Pract. 2004 Mar;10(2):88-94.
Switching from imipramine to sertraline in panic disorder.
Mavissakalian MR.
Case Western Reserve University, Cleveland, Ohio, USA.

BACKGROUND: There are no systematic switching studies of antidepressants in the treatment of panic disorder. The present pilot study examined the usefulness of switching from imipramine to sertraline in 18 patients diagnosed with panic disorder with agoraphobia. METHOD: 15 patients who had had an unsatisfactory outcome in a 24-week, open, weight-adjusted fixed-dose imipramine treatment study and 3 patients who had had a very satisfactory outcome but had subsequently relapsed following imipramine discontinuation were systematically switched to protocolized, 24-week open treatment with sertraline, 50-100 mg/day. Uniform measures of efficacy and side effects were used throughout the study. The net benefit obtained from the switch was assessed using an operationalized outcome grade ranging from 0-2, where 0 = inadequate duration of trial (dropouts) or non-response, 1 = partial response or full responders with side effects necessitating a change in treatment, and 2 = full response without complications. RESULTS: Based on paired t-tests, following the switch from imipramine to sertraline, a significant improvement was seen on phobic and panic symptomatologies, side effects, and overall outcome grade (from 0.67 [+/- 0.77] to 1.17 [+/- 0.92], p < or = 0.05]. Of the 18 patients who were switched to sertraline treatment, 9 (50%) clearly gained from the switch, 6 (33.3%) had an outcome similar to that achieved with imipramine, and 3 (16.7%) had a worse outcome following the switch. Of the 9 patients who failed to respond to or were unable to tolerate treatment with imipraminel (rating of 0), 3 patients (33.3%) achieved full and 2 patients (22.2%) achieved partial response after switching to sertraline. CONCLUSION: The findings in this study suggest that switching between antidepressants with established antipanic efficacy may be an effective strategy in the management of patients with panic disorder who have had an unsatisfactory outcome with the first antidepressant tried.

-----

Psychiatry Clin Neurosci. 2004 Apr;58(2):173-178.
Coping behavior in patients with panic disorder.
Yamada K, Fujii I, Akiyoshi J, Nagayama H.
Department of Neuropsychiatry, Oita Medical University, Oita, Japan.

The purpose of the present paper was to investigate the role of coping behavior in patients with panic disorder (PD). This was done by evaluating three items of coping behavior (seeking of social support, wishful thinking and avoidance) in the Ways of Coping Checklist. The subjects consisted of 30 patients with PD (26 with agoraphobia). Coping behavior and the severity of PD was investigated at baseline and at 24 months (the final outcome). At baseline there were no gender differences in coping behavior. The severity of panic attacks significantly correlated with that of agoraphobia. The baseline severity of PD (panic attacks and agoraphobia) did not correlate with coping behavior. At the outcome assessment there was no significant correlation between the severity of panic attack and coping behavior. The severity of agoraphobia at final outcome and the coping behavior (seeking of social support) at baseline were significantly correlated. In the group that had remission in agoraphobia (the good outcome group), the severity of agoraphobia at baseline was significantly lower and the seeking of social support coping behavior was significantly higher than that of the poor outcome group. No significant difference in panic attack severity was noted between the good and poor outcome groups. Discriminant analysis revealed that seeking of social support coping behavior was a significant discriminant factor of agoraphobia. Although these are preliminary data, special coping behavior might be related to improvement of agoraphobia in patients with PD.

-----

J Clin Psychiatry. 2004 Feb;65(2):244-8.
Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder.
Seedat S, Stein MB.
Anxiety and Traumatic Stress Disorders Program, Psychiatry Service, VA San Diego Healthcare System, San Diego, Calif.

BACKGROUND: Generalized social anxiety disorder (GSAD) is a pervasive form of social anxiety that affects approximately 5% of persons in the community. Among evidence-based pharmacologic treatments for the disorder, selective serotonin reuptake inhibitors (SSRIs) have become widely used and are known to be efficacious. Monotherapy with the benzodiazepine clonazepam is also efficacious for GSAD, but the adjunctive use of clonazepam with an SSRI to potentially improve outcomes has not been studied to date. METHOD: Twenty-eight patients (22 men and 6 women) with DSM-IV-defined GSAD were randomly assigned to receive double-blind clonazepam (or placebo), 1.0 to 2.0 mg/day (divided b.i.d.) along with open-label paroxetine, 20 to 40 mg/day, for 10 weeks. A 2-week taper of double-blind medication was followed by an additional 8 weeks of open-label paroxetine treatment (during which the dose of paroxetine could be increased to a maximum of 50 mg/day). Twenty-three patients (82%) met DSM-IV criteria for avoidant personality disorder. The patients' mean +/- SD age was 31.2 +/- 7.7 years, and their mean duration of illness was 12.1 +/- 5.8 years. Data were gathered from August 2001 to April 2002. RESULTS: Nineteen (68%) of 28 patients completed treatment. At the end of the 10-week double-blind treatment, there was a trend (p <.06) favoring the paroxetine/clonazepam group, who had a 79% response rate (Clinical Global Impressions-Global Improvement scale [CGI-I] score of 1 or 2) compared with a 43% response rate for the paroxetine/placebo group. However, no significant differences on other outcome measures were noted between the 2 groups in an intent-to-treat analysis, in terms of either very early (2-4 weeks) or not as early (5-10 weeks) responses during treatment. Dropout rates due to adverse events were rare (1 patient in each group), indicating that the paroxetine/clonazepam combination was well tolerated. CONCLUSION: Coadministration of clonazepam with an SSRI, in contrast to findings in panic disorder, did not lead to more rapid resolution of symptoms in GSAD. On the other hand, there is some evidence that the clonazepam-added group had superior global outcomes (e.g., as measured on the CGI-I), although power to detect such differences in this study was small. These observations suggest that a role for adjunctive benzodiazepines in patients with GSAD (e.g., for augmenting SSRI partial response or nonresponse) is deserving of further controlled investigation.

-----

CNS Spectr. 2003 May;8(5):356-62.
Cognitive-behavioral therapy for panic disorder: a review of treatment elements, strategies, and outcomes.
Rayburn NR, Otto MW.
Cognitive-Behavior Program, Department of Psychology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

This article provides an overview of cognitive-behavioral therapy (CBT) for panic disorder. CBT is currently considered a first-line treatment for panic disorder. It offers benefit after short-term intervention, typically consisting of 12-15 sessions conducted in either an individual or a group format. The treatment focuses on the elimination of the patterns that underlie and perpetuate the disorder. Through CBT, patients learn about the nature of the disorder and acquire a set of strategies that counter the fears of panic attacks themselves, and break the recurring cycle of anticipatory anxiety, panic, and agoraphobic avoidance. The collaborative format of treatment, and a focus on elimination of core fears may be factors in enhancing longer-term outcome. In this article, we review the efficacy of CBT as a first-line treatment, a strategy for medication nonresponders, a replacement strategy for patients who wish to discontinue pharmacotherapy, and a potential preventive strategy for at-risk individuals. We also discuss some of the complex issues involved with combination-treatment strategies.

-----

Eur Neuropsychopharmacol. 2003 May;13(3):153-64.
5-HT1A responsivity in patients with panic disorder before and after treatment with aerobic exercise, clomipramine or placebo.
Broocks A, Meyer T, Opitz M, Bartmann U, Hillmer-Vogel U, George A, Pekrun G, Wedekind D, Ruther E, Bandelow B.
Department of Psychiatry and Psychotherapy, University of Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany. broocks.a@psychiatry.mu-luebeck.de

Blunted neuroendocrine and physiological responses to the selective 5-HT(1A) receptor agonist, ipsapirone, have been observed in patients with panic disorder and/or agoraphobia (PDA). In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions, challenges with an oral dose of ipsapirone (0.3 mg/kg) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine, aerobic exercise and placebo. Before treatment, administration of ipsapirone was followed by significant increases of cortisol, anxiety and other psychopathological symptoms in comparison to the placebo challenge. In addition, a significant decrease of body temperature was observed. After the 10-week treatment period, the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group. In contrast, there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment. The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment. In conclusion, our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological, neuroendocrine and temperature responses to ipsapirone.

-----

Yonsei Med J. 2003 Feb;44(1):174-9.
Panic disorder in children and adolescents.
Diler RS.
Child Psychiatry Department, Cukurova University Faculty of Medicine, Balcali, Adana, Turkey. dilerrs@yahoo.com

Panic disorder (PD) in children and adolescents is a disabling and chronic condition, which is accompanied by psychosocial and academic difficulties both during adolescence and into adulthood. In this article, the prevalence, clinical characteristics, risk factors, comorbid states, differential diagnosis, and treatment of PD are reviewed. Although PD was thought to be rare in children and adolescents, the prevalence of PD in community samples ranges between 0.5% and 5.0, and in pediatric psychiatric clinics from 0.2% to 10%. Panic attacks are reported to be equally prevalent in males and females. Clinical studies have shown that the majority of the PD pediatric patients receiving consultation in clinics are older adolescents, Caucasian, female, and middle class. Up to 90% of children and adolescents with PD have other anxiety disorders (generalized anxiety disorder/overanxious disorder, separation anxiety disorder, social phobia or agoraphobia), or mood disorders (major depressive disorder or bipolar disorder). PD patients can be misdiagnosed or having neurologic, cardiovascular, pulmonary, or gastrointestinal illness. Psychoeducation and psychosocial treatments are recommended, and it appears that selective serotonin reuptake inhibitors (SSRIs) are a safe and promising treatment for children and adolescents with PD. The clinical characteristics, long-term course, and treatment of PD in children and adolescents needs to be further assessed by well-designed studies.

-----

Am J Psychiatry. 2003 Mar;160(3):513-21.
Capsulotomy for refractory anxiety disorders: long-term follow-up of 26 patients.
Ruck C, Andreewitch S, Flyckt K, Edman G, Nyman H, Meyerson BA, Lippitz BE, Hindmarsh T, Svanborg P, Mindus P, Asberg M.
Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden. christianrueck@home.se

OBJECTIVE: The objective of the present study was to evaluate the long-term efficacy and safety of capsulotomy in patients with anxiety disorders. METHOD: Twenty-six patients who had undergone bilateral thermocapsulotomy were followed up 1 year after the procedure and after a mean of 13 years. Primary diagnoses were generalized anxiety disorder (N=13), panic disorder (N=8), and social phobia (N=5). Measures of psychiatric status included symptom rating scales and neuropsychological testing. Ratings were done by psychiatrists not involved in patient selection or postoperative treatment. A quantitative magnetic resonance imaging (MRI) evaluation was conducted to search for common anatomic denominators. Seventeen of the 23 patients who were alive at long-term follow-up were followed up in person, and one was interviewed by telephone; the relatives of these 18 patients were interviewed. RESULTS: The reduction in anxiety ratings was significant both at 1-year and long-term follow-up. Seven patients, however, were rated as having substantial adverse symptoms; the most prominent adverse symptoms were apathy and dysexecutive behavior. Neuropsychological performance was significantly worse in the patients with adverse symptoms. No common anatomic denominator could be found in responders in the analysis of MRI scans. CONCLUSIONS: Thermocapsulotomy is an effective treatment for selected cases of nonobsessive anxiety but may carry a significant risk of adverse symptoms indicating impairment of frontal lobe functioning. These findings underscore the importance of face-to-face assessments of adverse symptoms.

-----

Int Clin Psychopharmacol. 2003 Jan;18(1):35-8.
Mirtazapine in the treatment of panic disorder: an open-label trial.
Sarchiapone M, Amore M, De Risio S, Carli V, Faia V, Poterzio F, Balista C, Camardese G, Ferrari G.
Institute of Psychiatry, Catholic University of Sacred Heart, Rome, Italy.

The aim of this open label trial was to evaluate mirtazapine tolerability and effectiveness in controlling symptomatology of patients with panic disorder. Forty-five patients with panic disorder, with or without agoraphobia, 11 of them with a comorbid diagnosis of major depression, were included. Patients were assessed with a structured psychiatric interview and their symptomatology evaluated with specific psychometric scales. Three study participants dropped out due to adverse events. Mirtazapine was administered at an established dose of 30 mg daily for 3 months. Patients were assessed at weeks 2 and 4, and then at monthly intervals. All psychometric measures showed statistically significant reductions in total scores at the rated time points, with a pronounced decline in number and intensity of panic attacks and anticipatory anxiety throughout the study. Mirtazapine was well tolerated as signified by the low discontinuation rate (6.3%), and all patients showed a significant symptomatic improvement. The improvement did not appear to be linked to the concurrent presence of a depressive illness.

-----

J Clin Psychiatry. 2003 Jun;64(6):654-62.
Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder.
Lepola U, Arato M, Zhu Y, Austin C.
Kuopio Psychiatric Research Clinic, Kuopio, Finland. ulla.lepola@iwn.fi

OBJECTIVE: To evaluate the efficacy and tolerability of sertraline and imipramine in patients with comorbid panic disorder and major depressive disorder. METHOD: Outpatients meeting a DSM-IV diagnosis of panic disorder and concurrent major depressive disorder were randomized in a 2:1 ratio to 26 weeks of double-blind treatment with either sertraline, in daily doses of 50 to 100 mg, or imipramine, in daily doses of 100 to 200 mg. Primary outcome measures were panic attack frequency (derived from patient diaries) and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: 138 patients were treated with sertraline (76% female; mean age = 40 years) and 69 with imipramine (70% female; mean age = 40 years). The symptoms of both major depressive disorder and panic disorder responded significantly and equivalently to both drugs. Endpoint improvement with sertraline versus imipramine, respectively, on the MADRS was 11.1 +/- 10.8 versus 11.2 +/- 10.4, and on the Clinical Global Impressions-Improvement scale (CGI-I) was 2.1 +/- 1.3 versus 2.4 +/- 1.6. Among study completers, CGI-I responder rates were 88% with sertraline and 91% with imipramine. Treatment outcome was concordant for both diagnoses in approximately 70% of patients and discordant in approximately 30%. Overall, sertraline was significantly better tolerated with significantly fewer discontinuations due to adverse events (11% vs. 22%; chi(2) = 4.39, df = 1, p =.04). CONCLUSION: Both sertraline and imipramine were found to be highly effective treatments for both major depressive disorder and panic disorder, with sertraline showing significantly greater tolerability and compliance during long-term treatment than imipramine.

-----

Hum Psychopharmacol. 2003 Apr;18(3):185-90.
Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a review.
Bourin M.
Neurobiology of Anxiety and Depression, Faculty of Medicine, Nantes, France.

Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. There is wide interindividual variation in the pharmacokinetics of paroxetine in adults as well as in the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment, however, serious adverse events are extremely rare even in overdose. A Pub Med search was used to collect information on the efficacy and tolerability in elderly patients. There are few studies of depression in the elderly and only one study in the old-old. In anxiety disorders including general anxiety disorder, panic disorder, obsessive-compulsive disorder and social anxiety, there are no studies at all in the elderly. However, the safety of the drug allows its prescription in the elderly. In summary, paroxetine is well tolerated in the treatment of depression in those between the ages of 65 and 75, although few studies have examined its use in those of 75 and older. Copyright 2002 John Wiley & Sons, Ltd.

-----

CNS Drugs. 2003;17(5):343-62.
Escitalopram : a review of its use in the management of major depressive and anxiety disorders.
Waugh J, Goa KL.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Asberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1-2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8-12 weeks in individual, randomised, placebo-controlled, double-blind investigations.The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use.CONCLUSIONS: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selective inhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders.

-----

CNS Drugs. 2003;17(3):143-51.
Role of pharmacogenomics in individualising treatment with SSRIs.
Mancama D, Kerwin RW.
Clinical Neuropharmacology, Institute of Psychiatry, Denmark Hill, London, England. d.mancama@iop.kcl.ac.uk

The introduction of the SSRIs has significantly transformed the pharmacological treatment of a range of psychiatric disorders. In particular, individuals affected by depression, panic disorder, obsessive-compulsive disorder and social phobia have benefited substantially from their use. Compared with the previous generation of psychotropic drugs, SSRIs offer an improved tolerability to therapy while maintaining a high level of efficacy. Nevertheless, despite these advantages, not all patients benefit from treatment; an appreciable proportion do not respond adequately, while others may react adversely. This necessitates a review of the initial treatment choice, often involving extended periods of illness while a more suitable therapy is sought. Such a scenario could be avoided were it possible to determine the most suitable drug prior to treatment. Several factors are postulated to influence outcome of drug therapy; most recently, pharmacogenetic studies have demonstrated a significant influence of genetic mechanisms on the efficacy of clinically prescribed drugs. This contribution, which is primarily a reflection of alterations in genes that encode drug-metabolising enzymes, drug receptors, transporters and second messengers, may be pertinent to the success of SSRI therapy. Attesting to this potential, studies to elucidate the influence of genetic processes on SSRI efficacy now represent a major focus of pharmacogenetics research. Current evidence emerging from the field suggests that gene variants within the serotonin transporter and cytochrome P450 drug-metabolising enzymes may bear a particular importance, though further corroboration of these findings is still warranted. At the same time, it appears likely that further key participating genes remain to be identified. By comprehensively delineating these genetic components, it is envisaged that this will eventually facilitate the development of highly sensitive protocols for individualising SSRI treatment.

-----

CNS Drug Rev. 2003 Spring;9(1):97-140.
Moclobemide: therapeutic use and clinical studies.
Bonnet U.
Department of Psychiatry and Psychotherapy, University of Essen, Germany. udo.bonnet@uni-essen.de

Moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA) and has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively studied in anxiety disorders. Nearly all meta-analyses and most comparative studies indicated that in the acute management of depression this drug is more efficacious than placebo and as efficacious as tricyclic (or some heterocyclic) antidepressants or selective serotonin reuptake inhibitors (SSRIs). There is a growing evidence that moclobemide is not inferior to other antidepressants in the treatment of subtypes of depression, such as dysthymia, endogenous (unipolar and bipolar), reactive, atypical, agitated, and retarded depression as with other antidepressants limited evidence suggests that moclobemide has consistent long-term efficacy. However, more controlled studies addressing this issue are needed. For patients with bipolar depression the risk of developing mania seems to be not higher with moclobemide than with other antidepressants. The effective therapeutic dose range for moclobemide in most acute phase trials was 300 to 600 mg, divided in 2 to 3 doses. While one controlled trial and one long-term open-label study found moclobemide to be efficacious in social phobia, three controlled trials subsequently revealed either no effect or less robust effects with the tendency of higher doses (600 - 900 mg/d) to be more efficacious. Two comparative trials demonstrated moclobemide to be as efficacious as fluoxetine or clomipramine in patients suffering from panic disorder. Placebo-controlled trials in this indication are, however, still lacking. A relationship between the plasma concentration of moclobemide and its therapeutic efficacy is not apparent but a positive correlation with adverse events has been found. Dizziness, nausea and insomnia occurred more frequently on moclobemide than on placebo. Due to negligible anticholinergic and antihistaminic actions, moclobemide has been better tolerated than tri- or heterocyclic antidepressants. Gastrointestinal side effects and, especially, sexual dysfunction were much less frequent with moclobemide than with SSRIs. Unlike irreversible MAO-inhibitors, moclobemide has a negligible propensity to induce hypertensive crisis after ingestion of tyramine-rich food ("cheese-reaction"). Therefore, dietary restrictions are not as strict. However, with moclobemide doses above 900 mg/d the risk of interaction with ingested tyramine might become clinically relevant. After multiple dosing the oral bioavailability of moclobemide reaches almost 100%. At therapeutic doses, moclobemide lacks significant negative effects on psychomotor performance, cognitive function or cardiovascular system. Due to the relative freedom from these side effects, moclobemide is particularly attractive in the treatment of elderly patients. Moclobemide is a substrate of CYP2C19. Although it acts as an inhibitor of CYP1A2, CYP2C19, and CYP2D6, relatively few clinically important drug interactions involving moclobemide have been reported. It is relatively safe even in overdose. The drug has a short plasma elimination half-life that allows switching to an alternative agent within 24 h. Since it is well tolerated, therapeutic doses can often be reached rapidly upon onset of treatment. Steady-state plasma levels are reached approximately at one week following dose adjustment. Patients with renal dysfunction require no dose reduction in contrast to patients with severe hepatic impairment. Cases of refractory depression might improve with a combination of moclobemide with other antidepressants, such as clomipramine or a SSRI. Since this combination has rarely been associated with a potentially lethal serotonin syndrome, it requires lower entry doses, a slower dose titration and a more careful monitoring of patients. Combination therapy with moclobemide and other serotonergic agents, or opioids, should be undertaken with caution, although no serious adverse events have been published with therapeutic doses of moclobemide to date. On the basis of animal data the combined use of moclobemide with pethidine or dextropropoxyphene should be avoided. There is no evidence that moclobemide would increase body weight or produce seizures. Some preclinical data suggest that moclobemide may have anticonvulsant property.

-----

Depress Anxiety. 2003;17(2):58-64.
Review of the long-term effectiveness of cognitive behavioral therapy compared to medications
in panic disorder.
Nadiga DN, Hensley PL, Uhlenhuth EH.
Department of Psychiatry, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.

Panic disorder is a recurrent and disabling illness. It is believed that Cognitive Behavioral Therapy (CBT) has a long-term protective effect for this disorder. This would offer CBT considerable advantage over medication management of panic disorder, as patients often relapse when they are tapered off their medications. This is a review of the literature about the long-term effectiveness of CBT. We searched for follow-up studies of panic disorder using CBT. Of the 78 citations produced in the initial search, most had major methodological flaws, including ignoring losses to follow-up, not accounting for interval treatment, and unclear reporting. Three papers met strict methodological criteria, and two of these demonstrated a modest protective effect of CBT in panic disorder patients. We make recommendations for well-designed studies involving comparisons of medications and cognitive behavior therapy. Depression and Anxiety 17:58-64, 2003. Copyright 2003 Wiley-Liss, Inc.

-----

Am Fam Physician. 2003 Feb 1;67(3):547-54.
Antidepressants: update on new agents and indications.
Ables AZ, Baughman OL 3rd.
Spartanburg Family Medicine Residency Program, Spartanburg, South Carolina 29303, USA. aables@srhs.com

A number of antidepressants have emerged in the U.S. market in the past two decades. Selective serotonin reuptake inhibitors have become the drugs of choice in the treatment of depression, and they are also effective in the treatment of obsessive-compulsive disorder, panic disorder, and social phobia. New indications for selective serotonin reuptake inhibitors include post-traumatic stress disorder, premenstrual dysphoric disorder, and generalized anxiety disorder. Extended-release venlafaxine has recently been approved by the U.S. Food and Drug Administration for the treatment of generalized anxiety disorder. Mirtazapine, which is unrelated to the selective serotonin reuptake inhibitors, is unique in its action--stimulating the release of norepinephrine and serotonin. The choice of antidepressant drug depends on the agent's pharmacologic profile, secondary actions, and tolerability. Sexual dysfunction related to the use of antidepressants may be addressed by reducing the dosage, switching to another agent, or adding another drug to overcome the sexual side effects. Augmentation with lithium or triiodothyronine may be useful in patients who are partially or totally resistant to antidepressant treatment. Finally, tapering antidepressant medication may help to avoid discontinuation syndrome or antidepressant withdrawal.

-----

J Clin Psychiatry. 2002;63 Suppl 14:17-21.
The management of panic disorder.
Sheehan DV.
University of South Florida Institute for Research in Psychiatry, Tampa 33613, USA. dsheehan@hsc.usf.edu

The evidence for benzodiazepines in panic disorder is compelling; along with the selective serotonin reuptake inhibitors (SSRIs), they are a standard treatment for panic and other anxiety disorders. However, extended-release formulations of these agents may prove to be as effective as the immediate-release formulations, and extended-release agents have clinical benefits that may make them more attractive treatments than the currently available, shorter-acting benzodiazepines. Because of their longer duration of action, extended-release benzodiazepines can protect against breakthrough anxiety and need to be taken only once or twice a day, which may improve compliance in some patients. Because the other standard treatments of panic disorder, the SSRIs, have a slow onset of action, adding an extended-release benzodiazepine to the treatment regimen for the initial 6 to 8 weeks could serve as an effective bridge until the desired SSRI effect is realized.

-----

Hum Psychopharmacol. 2002 Oct;17(7):329-33.
The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study.
Dannon PN, Iancu I, Grunhaus L.
Chaim Sheba Medical Center, Psychiatry Division, Tel Hashomer, Affiliated with the Sackler School of Medicine, Tel Aviv University, Israel. dannon@attglobal.net

BACKGROUND AND OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line treatment for panic disorder, although up to 30% of patients either do not respond to SSRIs or withdraw due to adverse events. Reboxetine, a selective norepinephrine reuptake inhibitor (selective NRI), is effective in treating depression and may alleviate depression-related anxiety. This study aimed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs. METHOD: In this 6-week, open-label study, 29 adult outpatients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day, titrated to a maximum of 8 mg/day over the first 10 days. Efficacy was assessed using the Panic Self-Questionnaire (PSQ), the Hamilton Rating Scale for Anxiety (HAM-A), the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment of Functioning (GAF) Scale. RESULTS: The 24 patients who completed the study responded well to reboxetine treatment. Significant improvement (p < 0.001) was observed in the number of daily panic attacks, and on the scales measuring anxiety, depression and functioning. Reboxetine was generally well tolerated. Five patients withdrew due to adverse events. CONCLUSIONS: Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation. Copyright 2002 John Wiley & Sons, Ltd.

-----

Am Fam Physician. 2002 Oct 15;66(8):1477-84.
What to do when SSRIs fail: eight strategies for optimizing treatment of panic disorder.
Zamorski MA, Albucher RC.
University of Michigan Medical School, Ann Arbor, USA.

Selective serotonin reuptake inhibitors (SSRIs) are the drug of choice for treatment of patients with panic disorder. Most patients have a favorable response to SSRI therapy; however, 30 percent will not be able to tolerate these drugs or will have an unfavorable or incomplete response. Strategies to improve management of such patients include optimizing SSRI dosing (starting at a low dose and slowly increasing the dose to reach the target dose) and ensuring an adequate trial before switching to a different drug. Benzodiazepines should be avoided but, when necessary, may be used for a short duration or may be used long-term in patients for whom other treatments have failed. Slower-onset, longer-acting benzodiazepines are preferred. All patients should be encouraged to try cognitive behavior therapy. Augmentation therapy should be considered in patients who do not have a complete response. Drugs to consider for use in augmentation therapy include benzodiazepines, buspirone, beta blockers, tricyclic antidepressants, and valproate sodium.

-----

J Clin Psychiatry. 2002 Sep;63(9):772-7.
A randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone.
Kampman M, Keijsers GP, Hoogduin CA, Hendriks GJ.
Department of Clinical Psychology and Personality, University of Nijmegen, The Netherlands. Kampman@psych.kun.nl

BACKGROUND: Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors (SSRIs) have proved to be effective in the treatment of panic disorder. The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone. METHOD: 161 patients with panic disorder with or without agoraphobia (DSM-IV criteria) underwent a manual-guided cognitive-behavioral therapy of 15 sessions. Forty-three unsuccessfully treated patients from this group were included in a double-blind, placebo-controlled, next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo. RESULTS: Overall, patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior (p < .05) and anxiety discomfort (p < .01), whereas patients in the cognitive-behavioral therapy plus placebo condition did not. Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition, from 0.4 to 1.0. CONCLUSION: Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality. The importance of timely evaluation of treatment results is emphasized.

-----

Acta Psychiatr Scand. 2002 Sep;106(3):163-7.
SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis.
Bakker A, van Balkom AJ, Spinhoven P.
Sint Lucas Andreas Hospital, Amsterdam, The Netherlands. a.bakker@slaz.nl

OBJECTIVE: To compare the short-term efficacy of selective serotonin reuptake inhibitors (SSRIs) vs. tricyclic antidepressants (TCAs) in the treatment of panic disorder (PD) a meta-analysis was conducted. METHOD: Included were 43 studies (34 randomized, nine open), pertaining to 53 treatment conditions, 2367 patients at pretest and 1804 at post-test. Outcome was measured with the proportion of patients becoming panic-free, and with pre/post Cohen's d effect sizes, calculated for four clinical variables: panic, agoraphobia, depression, and general anxiety. RESULTS: There were no differences between SSRIs and TCAs on any of the effect sizes, indicating that both groups of antidepressants are equally effective in reducing panic symptoms, agoraphobic avoidance, depressive symptomatology and general anxiety. Also the percentage of patients free of panic attacks at post-test did not differ. The number of drop-outs, however, was significantly lower in the group of patients treated with SSRIs (18%) vs. TCAs (31%). CONCLUSION: SSRIs and TCAs are equal in efficacy in the treatment of panic disorder, but SSRIs are tolerated better. Copyright Blackwell Munksgaard 2002.

-----

J Affect Disord. 2002 May;69(1-3):201-8.
Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder.
Simon NM, Safren SA, Otto MW, Sharma SG, Lanka GD, Pollack MH.
Anxiety Disorders Program, Massachusetts General Hospital and Harvard Medical School, 15 Parkman Street, WAC 815, Boston, MA 02114, USA. nsimon@partners.org

BACKGROUND: Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [Am. J. Psychiatry 155 (1998) 1], despite a paucity of data systematically examining outcome for periods greater than 3-6 months. It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder. METHODS: Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder, a prospective, naturalistic study. Participants were categorized by their maintenance treatment condition at remission: benzodiazepine alone (N = 45, 58%), antidepressant alone (N = 12, 16%), and combined treatment with a benzodiazepine and an antidepressant (N = 21, 27%). RESULTS: Approximately half (N = 36, 46%) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period, despite continued and adequate pharmacotherapy. There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy. LIMITATIONS: Interpretation of the data is limited by the naturalistic nature of the study, and by the relatively low sample size.CONCLUSIONS: This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy, despite continued treatment. In addition, the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy.

-----

J Psychopharmacol. 2002 Mar;16(1):5-14.
Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine.
Bell C, Forshall S, Adrover M, Nash J, Hood S, Argyropoulos S, Rich A, Nutt DJ.
Psychopharmacology Unit, School of Medical Sciences, University of Bristol, UK.

The neurobiological basis of panic disorder has not been clearly established, although a role for serotonin (5-HT) has been postulated. It is clear that drugs which increase 5-HT neurotransmission are effective in treating the condition but how they do so remains a point of debate. The aim of this study was to determine if lowering brain serotonin activity using the technique of tryptophan depletion provoked a short-term relapse of panic symptoms in patients with panic disorder who had responded to drug treatment. Fourteen patients with panic disorder who had responded to treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received an infusion of flumazenil (used as a pharmacological challenge) and placebo on each day. The tryptophan depleted drink produced an 87% reduction in plasma tryptophan concentration. Flumazenil produced a panic attack (defined by changes in the panic inventory) in seven out of 14 patients when tryptophan depleted and one out of 14 on the control day (p < 0.02). Three patients also experienced temporary depressive symptoms when tryptophan depleted, with no mood changes being seen on the control days. We conclude that rapid lowering of brain serotonin function can allow the precipitation of panic symptoms in response to flumazenil in panic disorder patients who have responded to treatment with an SSRI. This implies that in panic disorder increased 5-HT availability is important in maintaining the response to SSRIs.

-----

J Clin Psychiatry. 2002 Jan;63(1):31-7.
Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder.
Versiani M, Cassano G, Perugi G, Benedetti A, Mastalli L, Nardi A, Savino M.
Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil.

BACKGROUND: Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder. The introduction of SSRIs has enabled a greater understanding of the role of serotonin in the etiology of panic disorder; however, the role of norepinephrine has been more challenging to ascertain. The aim of this study was to determine the efficacy and tolerability of reboxetine, a novel selective norepinephrine reuptake inhibitor, in patients with panic disorder with and without agoraphobia. METHOD: Eighty-two patients (aged 18-65 years) with DSM-III-R panic disorder, with or without agoraphobia, were randomly assigned to receive 6 to 8 mg/day of reboxetine (42 patients) or placebo (40 patients) for 8 weeks in this placebo-controlled, parallel-group, double-blind clinical trial. RESULTS: Of the 82 patients enrolled in the trial, 75 were considered in the analysis (37 patients in the reboxetine group and 38 patients in the placebo group). At last assessment, there was a significant reduction in the mean number of panic attacks (range, 9.3-1.2) and phobic symptoms (range, 8.1-3.2) in the reboxetine group compared with the placebo group (ranges, 8.5-5.8 and 7.7-5.2, respectively; p < .05). Improvement in Hamilton Rating Scale for Depression, Hopkins Symptom Checklist-90, and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group. Adverse events reported more frequently with reboxetine than placebo included dry mouth (36% vs. 16%), constipation (27% vs. 22%), and insomnia (26% vs. 22%). CONCLUSION: Reboxetine was effective and well tolerated in the treatment of panic disorder.

-----

Hum Psychopharmacol. 2002 Oct;17(7):329-33.
The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study.
Dannon PN, Iancu I, Grunhaus L.
Chaim Sheba Medical Center, Psychiatry Division, Tel Hashomer, Affiliated with the Sackler School of Medicine, Tel Aviv University, Israel. dannon@attglobal.net

BACKGROUND AND OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line treatment for panic disorder, although up to 30% of patients either do not respond to SSRIs or withdraw due to adverse events. Reboxetine, a selective norepinephrine reuptake inhibitor (selective NRI), is effective in treating depression and may alleviate depression-related anxiety. This study aimed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs. METHOD: In this 6-week, open-label study, 29 adult outpatients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day, titrated to a maximum of 8 mg/day over the first 10 days. Efficacy was assessed using the Panic Self-Questionnaire (PSQ), the Hamilton Rating Scale for Anxiety (HAM-A), the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment of Functioning (GAF) Scale. RESULTS: The 24 patients who completed the study responded well to reboxetine treatment. Significant improvement (p < 0.001) was observed in the number of daily panic attacks, and on the scales measuring anxiety, depression and functioning. Reboxetine was generally well tolerated. Five patients withdrew due to adverse events. CONCLUSIONS: Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation. Copyright 2002 John Wiley & Sons, Ltd.

-----

Clin Pharmacokinet. 2002;41(15):1247-66.
Clinical pharmacokinetics of sertraline.
DeVane CL, Liston HL, Markowitz JS.
Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, Charleston, SC 29425-0742, USA. devanel@musc.edu

Sertraline is a naphthalenamine derivative with the predominant pharmacological action of inhibiting presynaptic reuptake of serotonin from the synaptic cleft. It was initially marketed for the treatment of major depressive disorder and is now approved for the management of panic disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Sertraline is slowly absorbed following oral administration and undergoes extensive first-pass oxidation to form N-desmethyl-sertraline, a weakly active metabolite that accumulates to a greater concentration in plasma than the parent drug at steady state. Sertraline is eliminated from the body by other metabolic pathways to form a ketone and an alcohol, which are largely excreted renally as conjugates. The elimination half-life of sertraline ranges from 22-36 hours, and once-daily administration is therapeutically effective. Steady-state plasma concentrations vary widely, up to 15-fold, in patients receiving usual antidepressant dosages between 50 and 150 mg/day. However, only sparse data have been published that support useful correlations between sertraline plasma concentrations and therapeutic or adverse effects to justify therapeutic drug monitoring. Sertraline has minimal inhibitory effects on the major cytochrome P450 enzymes, and few drug-drug interactions of clinical significance have been documented. Like other selective serotonin reuptake inhibitors, sertraline is well tolerated in therapeutic dosages and relatively safe in overdosage.

-----

Br J Psychiatry. 2001 Dec;179:514-8.
Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial.
Michelson D, Allgulander C, Dantendorfer K, Knezevic A, Maierhofer D, Micev V, Paunovic VR, Timotijevic I, Sarkar N, Skoglund L, Pemberton SC.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.

BACKGROUND: Although serotonin reuptake inhibitors are effective in panic disorder, questions concerning whether doses associated with antidepressant efficacy are also effective for panic disorder remain. AIMS: To assess the efficacy of the usual antidepressant dose of fluoxetine in treating full panic attacks. METHOD: Patients with panic disorder were randomised to placebo or to fluoxetine initiated at 10 mg daily for 1 week and then increased to 20 mg daily. The trial lasted 12 weeks, but after 6 weeks patients who had failed to achieve a satisfactory response were eligible for dose escalation to a maximum of 60 mg of fluoxetine daily. RESULTS: Fluoxetine was associated with a statistically significantly greater proportion of panic-free patients compared with placebo after 6 weeks and at end-point. CONCLUSIONS: Fluoxetine at a dose of 20 mg daily is safe and efficacious in reducing symptoms of panic disorder. Patients who fail to obtain a satisfactory response at 20 mg daily may benefit from further dose increases.

-----

Am J Psychiatry. 2001 Dec;158(12):1993-8.
Emotion-focused psychotherapy for patients with panic disorder.
Shear MK, Houck P, Greeno C, Masters S.
Anxiety Disorders Prevention Program, Department of Psychiatry, University of Pittsburgh Medical Center, PA, USA. shearmk@msx.umpc.edu

OBJECTIVE: Recent studies have suggested that most patients treated for panic disorder receive forms of psychotherapy other than cognitive behavior therapy, even though there is little information about the efficacy of such treatments or how they compare to proven active treatments. The authors compared one of these other forms, emotion-focused psychotherapy (given to 30 patients with panic disorder), to results obtained with recommended standard treatment (either cognitive behavior therapy [N=36] or imipramine [N=22]). The authors also compared emotion-focused psychotherapy to results obtained in subjects given pill placebo (N=24). METHOD: Subjects met DSM-IV criteria for panic disorder with no more than mild agoraphobia. Treatment consisted of approximately 3 months of weekly visits followed by 6 monthly maintenance visits. Assessments were conducted after each treatment phase and at a follow-up visit after 6 months of no treatment. RESULTS: Emotion-focused psychotherapy was less effective for symptoms of panic disorder than treatment with either cognitive behavior therapy or imipramine; results obtained with emotion-focused psychotherapy after the acute and maintenance phases were similar to those seen with placebo. Treatment expectations were not different among the different groups. Patients receiving emotion-focused psychotherapy had the highest completion rate. CONCLUSIONS: The results suggest that emotion-focused psychotherapy (a supportive form of psychotherapy) has low efficacy for the treatment of panic disorder. However, emotion-focused psychotherapy may be superior to medical management in helping patients stay in treatment.

-----

Acta Psychiatr Scand. 2001 Oct;104(4):289-98.
Sertraline treatment of panic disorder: results of a long-term study.
Rapaport MH, Wolkow R, Rubin A, Hackett E, Pollack M, Ota KY.
Department of Psychiatry, University of California at San Diego and Psychiatric Service San Diego Veterans, Affairs Healthcare System, 8950 Villa La Jolla Dr., La Jolla, CA 92037, USA.

OBJECTIVE: To investigate the long-term efficacy, prevention of relapse and safety of sertraline in the treatment of panic disorder. METHOD: This study consisted of 52 weeks of open-label sertraline treatment (n=398) followed by a 28 weeks of a double-blind, placebo-controlled discontinuation trial (n=183). RESULTS: Ninety-three patients were randomized to sertraline and 90 were randomized to placebo. Discontinuation due to insufficient clinical response occurred in 23.6% of placebo-treated patients and 12.0% of sertraline-treated patients (log-rank test, P=0.040). Thirty-three per cent of placebo-treated patients had an exacerbation of panic symptomatology, versus 13% of sertraline-treated patients (log-rank test, P=0.005). Abrupt cessation of sertraline resulted in dizziness (4.3% sertraline vs. 16.9% placebo; P=0.007) and insomnia (4.3% sertraline vs. 15.7% placebo; P=0.013) occurring at significantly higher rates. CONCLUSION: Long-term sertraline treatment was effective in preventing relapse of panic disorder, well tolerated and associated with minimal discontinuation symptoms.

-----

Int Clin Psychopharmacol. 2001 Nov;16(6):363-8.
The effect of mirtazapine in panic disorder: an open label pilot study with a single-blind placebo
run-in period.
Boshuisen ML, Slaap BR, Vester-Blokland ED, den Boer JA.
Department of Psychiatry, AZG, Groningen, The Netherlands.

In this open label pilot study, we studied the efficacy of mirtazapine (Remeron) in panic disorder. Twenty-eight patients with a DSM-IV diagnosis of panic disorder, with or without agoraphobia (10 males/18 females), were included and 19 patients completed the study. The 15-week trial started with a 3-week single-blind placebo run-in period. After this run-in period, the 12-week active treatment phase started. As primary efficacy measures, we studied the decrease in the number of full symptom panic attacks and the number of patients completely free of panic during the last 3 weeks of the study. Seventy-four percent of the patients were considered responders, according to a decrease of at least 50% in panic attack frequency. All primary and secondary efficacy measures showed a significant improvement from the second week of active treatment onwards to endpoint. The main side-effects were different from the usual side-effects in selective serotonin reuptake inhibitors (SSRIs) (initial drowsiness, weight gain and pain in the legs). The results of this open label study in panic disorder suggest that mirtazapine seems to be a fast and effective treatment alternative for SSRIs in panic disorder.

-----

J Psychother Pract Res. 2001 Fall;10(4):239-45.
A pilot open trial of brief psychodynamic psychotherapy for panic disorder.
Milrod B, Busch F, Leon AC, Aronson A, Roiphe J, Rudden M, Singer M, Shapiro T, Goldman H, Richter D, Shear MK.
Weill Medical College of Cornell University, Payne Whitney Clinic, New York, NY 10021, USA.

This is a complete report of an open trial of manualized psychodynamic psychotherapy for treatment of panic disorder, Panic-Focused Psychodynamic Psychotherapy (PFPP). Twenty-one patients with PD were entered into a trial of twice-weekly, 24-session treatment. Sixteen of 21 experienced remission of panic and agoraphobia. Treatment completers with depression also experienced remission of depression. Improvements in symptoms and in quality of life were substantial and consistent across all measured areas. Symptomatic gains were maintained over 6 months. This report was prepared specifically to describe 6-month follow-up on these patients. Psychodynamic psychotherapy appears to be a promising nonpharmacological treatment for panic disorder.

The Panic Disorder FileSM Compiled and Maintained by    The Center for Current Research, Inc. 708 Aubrey Avenue • Ardmore PA USA 19003 Phone: 610-649-3165 • Email: customerservice@lifestages.com Website: www.lifestages.com

©Copyright 1992-date by The Center for Current Research. The Panic Disorder File is a proprietary compilation of the Center for Current Research. The information in the File is solely for your use, and the use of your family, friends, and doctors. The information is the property of the individual researchers and institutions that produced it. It is an infringement of copyright law to attempt to "resell" the information as it is presented here.