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Latest Research on Panic Disorder
     
Acta Psychiatr Scand. 2008 Apr;117(4):260-70. Epub 2008 Feb 26.
Is a combined therapy more effective than either CBT or SSRI alone? Results of a multicenter trial on panic disorder with or without agoraphobia.
van Apeldoorn FJ, van Hout WJ, Mersch PP, Huisman M, Slaap BR, Hale WW 3rd, Visser S, van Dyck R, den Boer JA.
University Medical Center Groningen, Groningen, The Netherlands. f.j.van.apeldoorn@psy.umcg.nl

OBJECTIVE: To establish whether the combination of cognitive-behavioral therapy (CBT) and pharmacotherapy (SSRI) was more effective in treating panic disorder (PD) than either CBT or SSRI alone, and to evaluate any differential effects between the mono-treatments. METHOD: Patients with PD (n = 150) with or without agoraphobia received CBT, SSRI or CBT + SSRI. Outcome was assessed after 9 months, before medication taper. RESULTS: CBT + SSRI was clearly superior to CBT in both completer and intent-to-treat analysis (ITT). Completer analysis revealed superiority of CBT + SSRI over SSRI on three measures and no differences between CBT and SSRI. ITT analysis revealed superiority of SSRI over CBT on four measures and no differences between CBT + SSRI and SSRI. CONCLUSION: Both the mono-treatments (CBT and SSRI) and the combined treatment (CBT + SSRI) proved to be effective treatments for PD. At post-test, CBT + SSRI was clearly superior to CBT, but differences between CBT + SSRI and SSRI, and between SSRI and CBT, were small.

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J Clin Psychiatry. 2008 Feb 13;:e1-e7 [Epub ahead of print]
Predictors and Time Course of Response Among Panic Disorder Patients Treated With Cognitive-Behavioral Therapy.
Aaronson CJ, Shear MK, Goetz RR, Allen LB, Barlow DH, White KS, Ray S, Money R, Saksa JR, Woods SW, Gorman JM.
From the Department of Psychiatry, Mount Sinai School of Medicine, New York, N.Y. (Dr. Aaronson); Columbia University School of Social Work, New York, N.Y., and the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pa. (Dr. Shear); the Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, N.Y. (Dr. Goetz); the Center for Anxiety and Related Disorders at Boston University, Boston, Mass. (Drs. Allen and Barlow); the Department of Psychology, University of Missouri–Saint Louis (Dr. White); North Shore/Long Island Jewish Health System, Zucker Hillside Hospital, Glen Oaks, N.Y. (Ms. Ray); the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. (Mr. Money and Drs. Saksa and Woods); and Comprehensive NeuroScience, Inc., White Plains, N.Y. (Dr. Gorman).

OBJECTIVE: Cognitive-behavioral therapy (CBT) is well documented as an efficacious treatment for panic disorder. We provided open CBT treatment to patients who subsequently participated in a maintenance treatment study. This article reports on predictors and trajectory of response in 381 participants who completed treatment at 4 sites. METHOD: Participants who met criteria for panic disorder with or without agoraphobia (N = 381) completed assessment and entered treatment. Of these, 256 completed 11 sessions of CBT delivered by trained and supervised research therapists. Raters trained to reliability obtained demographic data and administered structured diagnostic interviews and the Hamilton Rating Scales for Depression and Anxiety and the Panic Disorder Severity Scale (PDSS) measures at baseline and posttreatment. We obtained self-report (SR) measures of anxiety sensitivity and adult separation anxiety at baseline and posttreatment and PDSS-SR ratings weekly. The study was conducted between November 1999 and July 2002. RESULTS: Treatment response rate was 65.6% for completers and 44.1% for the intent-to-treat sample. Greater severity of panic disorder and lower levels of adult separation anxiety predicted response. Beginning at week 4, responders showed greater mean decreases in PDSS scores than non-responders and maintained the advantage throughout the treatment. By week 6, 76% of responders, compared to 36% of nonresponders, recorded PDSS scores at least 40% below baseline on 2 consecutive weeks (odds ratio = 5.42, 95% CI = 3.10 to 9.48). CONCLUSION: These results suggest that CBT is just as effective for more severe panic disorder patients as it is for those with less severe panic disorder, regardless of other comorbid disorders, including agoraphobia. However, patients experiencing adult separation anxiety disorder are less likely to respond. Our results further inform clinicians that many people who will respond to 11 weeks of treatment will have done so by the middle of the treatment.

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J Anxiety Disord. 2008 Jan 18 [Epub ahead of print]
Is internet-based CBT for panic disorder and agoraphobia as effective as face-to-face CBT?
Kiropoulos LA, Klein B, Austin DW, Gilson K, Pier C, Mitchell J, Ciechomski L.
Department of General Practice, School of Primary Health Care, Monash University, Building 1, 270 Ferntree Gully Road, Notting Hill, Victoria 3168, Australia.

This study compared Panic Online (PO), an internet-based CBT intervention, to best-practice face-to-face CBT for people with panic disorder with or without agoraphobia. Eighty-six people with a primary diagnosis of panic disorder were recruited from Victoria, Australia. Participants were randomly assigned to either PO (n=46) or best practice face-to-face CBT (n=40). Effects of the internet-based CBT program were found to be comparable to those of face-to-face CBT. Both interventions produced significant reductions in panic disorder and agoraphobia clinician severity ratings, self reported panic disorder severity and panic attack frequency, measures of depression, anxiety, stress and panic related cognitions, and displayed improvements in quality of life. Participants rated both treatment conditions as equally credible and satisfying. Participants in the face-to-face CBT treatment group cited higher enjoyment with communicating with their therapist. Consistent with this, therapists' ratings for compliance to treatment and understanding of the CBT material was higher in the face-to-face CBT treatment group. PO required significantly less therapist time than the face-to-face CBT condition.

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Curr Opin Psychiatry. 2008 Jan;21(1):51-64.
Anxiety disorders and suicidal behaviour: an update.
Hawgood J, De Leo D.
Australian Institute for Suicide Research & Prevention, Griffith University, World Collaborating Centre for Suicide Research and Training, Brisbane, Australia.

PURPOSE OF REVIEW: The primary aim of this review is to present the main findings from the literature published between January 2006 and May 2007 on anxiety and suicidal behaviour. The secondary aim is to present critical comments on methodological issues, highlighting areas for future research. RECENT FINDINGS: Traditionally, anxiety disorders have not been viewed as independent risk factors for suicidal behaviour, and therefore assessment of anxiety disorders has not been particularly emphasized in clinical enquiries and suicide screening tools. This review identifies evidence suggesting that specific anxiety disorders (e.g. generalized anxiety disorder, panic disorder and obsessive-compulsive disorder) may be independently associated with suicidality, to which they particularly contribute when they are co-morbid with bipolar disorder, depression, schizophrenia, or post-traumatic stress disorder, in both child/adolescent and adult populations. SUMMARY: Despite methodological issues preventing firm conclusions from being drawn in most cases, these findings should prompt clinicians to evaluate more specifically the impact of anxiety disorders on suicidal behaviour, particularly when they are co-morbid. Further research into treatment of anxiety disorders in relation to preventing suicide is required.

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Respir Med. 2008 Jan 25 [Epub ahead of print]
Mental disorders in chronic obstructive pulmonary disease (COPD).
Vögele C, von Leupoldt A.
Clinical and Health Psychology Research Centre, School of Human and Life Sciences, Whitelands College, Roehampton University, Holybourne Avenue, London SW15 4JD, UK.

Recent research using questionnaire measures has demonstrated high prevalence rates of mental disorders in chronic obstructive pulmonary disease (COPD). However, clinical interviews and clinical rather than healthy control groups have rarely been employed. The aim of the present study was to assess mental disorders in patients with COPD with advanced methodology, to identify moderating factors explaining mental co-morbidities and to compare results with a clinical control group without COPD. A standardized clinical interview (F-DIPS) and a range of questionnaires were used to assess mental disorders, perceived physical symptoms and cognitions in 20 hospitalized patients with mild-to-moderate COPD (mean FEV(1)/VC (%)=61.3). Results were compared with a hospitalized clinical control group without pulmonary dysfunction (CCG; N=20). Results showed that 55% of patients with COPD received a diagnosis of a mental disorder compared to 30% of CCG patients. All principal mental diagnoses in the COPD group were anxiety disorders (especially Panic Disorder with Agoraphobia), while CCG patients received a wider range of diagnoses (anxiety, pain, alcohol abuse). There was no systematic association between anxiety levels and respiratory function in the whole COPD group, but a positive correlation between anxiety levels and perceived physical symptoms (p<0.001) as well as negative cognitions (p<0.001 and p<0.05, respectively) for COPD patients with anxiety disorder (N=11). The present results confirm the high prevalence rate of anxiety in patients with COPD and suggest further that anxiety in COPD patients may be mediated by cognitive processes. These findings are discussed in terms of their implications for treatment.

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BMC Psychiatry. 2007 Dec 20;7(1):73 [Epub ahead of print]
Can pill placebo augment cognitive-behavior therapy for panic disorder?
Furukawa TA, Watanabe N, Omori IM, Churchill R.

ABSTRACT: BACKGROUND: In a number of drug and psychotherapy comparative trials, psychotherapy-placebo combination has been assumed to represent psychotherapy. Whether psychotherapy plus pill placebo is the same as psychotherapy alone is an empirical question which however has to date never been examined systematically. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) that directly compared cognitive-behavior therapy (CBT) alone against CBT plus pill placebo in the treatment of panic disorder. RESULTS: Extensive literature search was able to identify three relevant RCTs. At the end of the acute phase treatment, patients who received CBT plus placebo had 26% (95%CI: 2 to 55%) increased chances of responding than those who received CBT alone. At follow-up the difference was no longer statistically significant (22%, 95%CI: -10% to 64%). CONCLUSIONS: The act of taking a pill placebo may enhance the placebo effect already contained in the effective psychotherapeutic intervention during the acute phase treatment. Theoretically this is an argument against the recently claimed null hypothesis of placebo effect in general and clinically it may point to some further room for enhancing the psychotherapeutic approach for panic disorder.

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Clin Neuropharmacol. 2007 November/December;30(6):326-334.
A Naturalistic Long-Term Comparison Study of Selective Serotonin Reuptake Inhibitors in the Treatment of Panic Disorder.
Dannon PN, Iancu I, Lowengrub K, Gonopolsky Y, Musin E, Grunhaus L, Kotler M.
*Rehovot Community Mental Health and Rehabilitation Clinic (affiliated to Ness Ziona-Beer Yaakov Medical Complex), †Tel Aviv University Sackler School of Medicine, and ‡Psychiatry Department C, Chaim Sheba Medical Center, Tel Hashomer, Israel.

OBJECTIVES:: Selective serotonin reuptake inhibitors (SSRIs) are currently considered as the first drug of choice in the treatment of panic disorder (PD). The aim of this long-term, naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD. Outcome measures included relapse rates and adverse effects. METHODS:: Two hundred patients with PD were enrolled in our study. All subjects met DSM-IV criteria for PD or PD with agoraphobia (PDA). All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram (n = 50), fluoxetine (n = 50), fluvoxamine (n = 50), or paroxetine (n = 50) in a randomized, nonblinded fashion. Both the treating psychiatrist and the patients were not blind to the assigned treatment, but the clinician raters were blind to the study medication. The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists. The Panic Self-Questionnaire, which is a self-report scale, was administered at baseline and then once per month during the duration of the 12-month study. The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study. Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits. The body weight of study subjects was measured at baseline, and then at the 12th month visit end point. RESULTS:: Of 200 patients who entered the study, 127 patients (63.5%) completed the full 12-month protocol. Retention rates were highest for paroxetine (76% [38/50]), intermediate for citalopram (68% [34/50]) and fluvoxamine (60% [30/50]), and lowest for fluoxetine (50% [25/50]). Patients who completed the 12-month protocol responded favorably to the study treatment. The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8. At visits on months 3, 6, 9, and 12, however, there were no statistically significant differences between the 4 groups in relapse rates (defined as the occurrence of 1 or more panic attacks during the previous week of treatment) (F1,127 = 0.17; P = 0.13 [not statistically significant]). At the 12th month end point, patients in all 4 treatment groups had a statistically significant increase in body weight. Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment. Reports of sexual adverse effects at the 12th month visit were similar in the citalopram, fluoxetine, and paroxetine groups, but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit. CONCLUSIONS:: Most of our PD patients responded well to 12-month treatment with either citalopram, fluoxetine, fluvoxamine, or paroxetine, and the overall response rate was equal after the first 4 weeks of treatment. Although patients treated with paroxetine had the lowest dropout rates during the initiation phase, they had the highest rate of adverse effects as measured at the 12th month visit. Conversely, patients in the fluvoxamine group had the highest dropout rate (which was primarily caused by adverse effects in the initiation phase of treatment.); however, patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents. Overall, when measured at the 12th month visit, monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine. In addition, monotherapy with paroxetine, citalopram, and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine.

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J Clin Psychiatry. 2007 Nov;68(11):e26.
Recognition and treatment of panic disorder.
Lydiard RB.
Southeast Health Consultants, Charleston, SC, USA.

Panic disorder is a common, disabling condition that affects 3% to 5% of the world's population. Although it is treatable, panic disorder goes unrecognized and untreated in many patients. Patients with panic disorder have an increased risk for other psychiatric disorders, especially other anxiety disorders, and panic disorder is associated with other medical conditions such as migraines, fibromyalgia, and irritable bowel syndrome. Clinicians treating panic disorder must be able to recognize the disorder, differentiate it from other disorders in which panic attacks are part of the symptomatology, and map out an individualized treatment plan for each patient. This presentation discusses the importance of collaboration between doctor and patient and details available treatment options, including antidepressants, benzodiazepines, and cognitive-behavioral therapy.

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Psychopharmacol Bull. 2007;40(3):32-40.
An open-label study of tiagabine in panic disorder.
Sheehan DV, Sheehan KH, Raj BA, Janavs J.
University of South Florida College of Medicine, Tampa, FL.

gamma-aminobutyric acid (GABA) has been implicated in the pathophysiology of anxiety disorders, including panic. Tiagabine, a selective GABA reuptake inhibitor (SGRI), has been shown to reduce symptoms of anxiety. This pilot study evaluated the efficacy and safety of tiagabine in patients with panic disorder. Male and female outpatients aged 18-64 years with a DSM-IV diagnosis of severe to moderately severe panic disorder (with or without agoraphobia) received open-label tiagabine 2-20 mg/day for 10 weeks. Outcome assessments included the Sheehan Panic Disorder Scale (SPS), Panic Disorder Severity Scale (PDSS), Bandelow Panic and Agoraphobia Scale (PAS), Hamilton Rating Scale for Anxiety (HAM-A), 21-point Clinician Global Improvement Scale (CGI-21), 21-point Patient Global Improvement (PGI-21) and the Sheehan Disability Scale (SDS). Scores were recorded at baseline and weekly intervals thereafter. Adverse events were monitored throughout the study. Of the 28 patients who enrolled in the study, 23 had one post-baseline visit and were available for LOCF outcome analysis. Although statistically significant reductions from baseline were observed for all of the outcome measures, the percentage improvements on individual scales were only in the 25-32% range which is not clinically significant. Tiagabine was generally well tolerated; the most common adverse events were nausea, dizziness and headaches. Only one patient discontinued tiagabine due to adverse events. These findings suggest that administration of tiagabine may be of little benefit in patients with panic disorder.

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Depress Anxiety. 2007 Oct 25 [Epub ahead of print]
Cognitive style, alprazolam plasma levels, and treatment response in panic disorder.
Uhlenhuth EH, Starcevic V, Qualls C, Antal EJ, Matuzas W, Javaid JI, Barnhill J.
Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico.

This study investigated an anxiety-prone cognitive style (measured by the Anxious Thoughts and Tendencies Questionnaire, AT&T) as a predictor of the acute response to increasing alprazolam plasma levels in panic disorder. Panic disorder patients (n=26) were treated with escalating doses of alprazolam for 4 weeks, then a fixed dose of 1 mg four times a day for 4 weeks. At 0, 1, 2, 3, 4, 6, and 8 weeks, trough alprazolam plasma levels; clinical, self-report, and performance measures; and vital signs were assessed. Panic attack data were from daily diaries. The repeated response measures were analyzed in relation to alprazolam plasma levels using SAS GENMOD, with patients classified as high or low on the baseline AT&T. Panic attacks, anticipatory anxiety, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, and clinicians' global ratings improved with increasing alprazolam plasma levels. Hopkins Symptom Checklist-90 Anger-Hostility; Profile of Mood States Vigor, Confusion, and Friendliness; and speed and accuracy of performance worsened. Patients with high AT&T scores were worse throughout the study on situational panics, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, the Hamilton Rating Scale for Depression, and Clinical Global Improvement; most Hopkins Symptom Checklist-90 clusters; Profile of Mood States Anxiety, Depression, and Confusion; and Continuous Performance Task omissions. We conclude that in panic disorder: (1) alprazolam has a broad spectrum of clinical activity related to plasma levels in individual patients; (2) sedation, disinhibition, and performance deficits may persist for at least a month after dose escalation ends; (3) marked anxiety-prone cognitions predict more symptoms throughout treatment, but do not modify the response to alprazolam and therefore should not influence the choice of alprazolam as treatment. Depression and Anxiety 0:1-9, 2007. Published 2007 Wiley-Liss, Inc.

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Can Fam Physician. 2007 Oct;53(10):1686-93.
[Early detection and treatment of panic disorder with or without agoraphobia: update]
[Article in French]
Foldes-Busque G, Marchand A, Landry P.
Département de psychologie, Université du Québec à Montréal, C.P. 8888 succursale Centre-ville, Montréal, QC. marchand.andre@uqam.ca

OBJECTIVE: To describe for family physicians screening, diagnosis, and treatment of panic disorder with or without agoraphobia (PD/A). QUALITY OF EVIDENCE: Articles were identified through PsycLIT, PsyINFO, and MEDLINE (1985 to 2006) using the terms panic disorder, psychotherapy, psychosocial treatment, treatment, and pharmacotherapy. Recommendations on treatment choices and guidelines are based on data from high-quality studies only. Information about assessment and diagnosis of PD/A is supported by the most recent epidemiologic studies, as well as expert consensus and opinion. MAIN MESSAGE: Panic disorder with or without agoraphobia is a psychiatric disease frequently encountered in primary care. It appears to be underdiagnosed and undertreated in this medical setting. Early successful screening requires a focus on unexplained symptoms and specific questions aimed at identifying panic attacks and their meaning for patients. The treatment of choice for PD/A is cognitive-behavioral therapy administered by a specialized psychologist or psychiatrist. When such therapy is hard to come by or unavailable, family physicians can prescribe drug therapy. CONCLUSION: Family physicians can contribute greatly to early detection and treatment of PD/A.

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J Consult Clin Psychol. 2007 Aug;75(4):513-22.
Specificity of treatment effects: Cognitive therapy and relaxation for generalized anxiety and panic disorders.
Siev J, Chambless DL.
Department of PsychologyUniversity of Pennsylvania, Philadelphia, PA, US. jsiev@psych.upenn.edu.

The aim of this study was to address claims that among bona fide treatments no one is more efficacious than another by comparing the relative efficacy of cognitive therapy (CT) and relaxation therapy (RT) in the treatment of generalized anxiety disorder (GAD) and panic disorder without agoraphobia (PD). Two fixed-effects meta-analyses were conducted, for GAD and PD separately, to review the treatment outcome literature directly comparing CT with RT in the treatment of those disorders. For GAD, CT and RT were equivalent. For PD, CT, which included interoceptive exposure, outperformed RT on all panic-related measures, as well as on indices of clinically significant change. There is ample evidence that both CT and RT qualify as bona fide treatments for GAD and PD, for which they are efficacious and intended to be so. Therefore, the finding that CT and RT do not differ in the treatment of GAD, but do for PD, is evidence for the specificity of treatment to disorder, even for 2 treatments within a CBT class, and 2 disorders within an anxiety class. ((c) 2007 APA, all rights reserved).

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Acupunct Med. 2007 Jun;25(1-2):1-10.
Acupuncture for anxiety and anxiety disorders--a systematic literature review.
Pilkington K, Kirkwood G, Rampes H, Cummings M, Richardson J.
School of Integrated Health, University of Westminster, London, UK. K.Pilkington@westminster.ac.uk

INTRODUCTION: The aim of this study was to evaluate the evidence for the efficacy of acupuncture in the treatment of anxiety and anxiety disorders by systematic review of the relevant research. METHODS: Searches of the major biomedical databases (MEDLINE, EMBASE, ClNAHL, PsycINFO, Cochrane Library) were conducted between February and July 2004. Specialist complementary medicine databases were also searched and efforts made to identify unpublished research. No language restrictions were imposed and translations were obtained where necessary. Study methodology was appraised and clinical commentaries obtained for studies reporting clinical outcomes. RESULTS: Twelve controlled trials were located, of which 10 were randomised controlled trials (RCTs). Four RCTs focused on acupuncture in generalised anxiety disorder or anxiety neurosis, while six focused on anxiety in the perioperative period. No studies were located on the use of acupuncture specifically for panic disorder, phobias or obsessive-compulsive disorder. In generalised anxiety disorder or anxiety neurosis, it is difficult to interpret the findings of the studies of acupuncture because of the range of interventions against which acupuncture was compared. All trials reported positive findings but the reports lacked many basic methodological details. Reporting of the studies of perioperative anxiety was generally better and the initial indications are that acupuncture, specifically auricular acupuncture, is more effective than acupuncture at sham points and may be as effective as drug therapy in this situation. The results were, however, based on subjective measures and blinding could not be guaranteed. CONCLUSIONS: Positive findings are reported for acupuncture in the treatment of generalised anxiety disorder or anxiety neurosis but there is currently insufficient research evidence for firm conclusions to be drawn. No trials of acupuncture for other anxiety disorders were located. There is some limited evidence in favour of auricular acupuncture in perioperative anxiety. Overall, the promising findings indicate that further research is warranted in the form of well designed, adequately powered studies.

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Psychopharmacology (Berl). 2007 Jun 23; [Epub ahead of print]
A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder.
Pollack M, Mangano R, Entsuah R, Tzanis E, Simon NM.
Massachusetts General Hospital, Simches Research Building, 185 Cambridge Street, Suite 2200, 2nd Floor, Boston, MA, 02114-2790, USA, mpollack@partners.org.

RATIONALE: Few randomized, placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder. OBJECTIVES: The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release (ER) with placebo in treating panic disorder. Secondary objectives included comparing paroxetine with venlafaxine ER and placebo. METHODS: Outpatients aged >/=18 years (placebo, n = 157; venlafaxine ER 75 mg, n = 156; venlafaxine ER 225 mg, n = 160; paroxetine, n = 151), with a primary diagnosis of panic disorder (+/-agoraphobia) based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for >/=3 months were randomly assigned to receive venlafaxine ER (titrated to 75 mg/day or 225 mg/day), paroxetine (titrated to 40 mg/day), or placebo for 12 weeks. The primary efficacy measure was the percentage of patients free of full-symptom panic attacks (>/= four symptoms) at endpoint. Key secondary outcomes included the Panic Disorder Severity Scale (PDSS) mean score change and response. RESULTS: At endpoint, all active treatment groups showed a significantly (P < 0.01) greater proportion of patients free of full-symptom panic attacks, compared with placebo, and were superior (P < 0.05) on most secondary measures. The venlafaxine ER 225 mg group had significantly (P < 0.05) greater mean PDSS score improvement than the paroxetine group (-12.58 vs -11.87) and a significantly higher proportion of patients free of full symptom panic attacks (70.0 vs 58.3%). Both drugs were generally well tolerated. CONCLUSION: Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder.

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Appl Psychophysiol Biofeedback. 2007 Jun;32(2):89-98. Epub 2007 May 23.
Psychophysiological effects of breathing instructions for stress management.
Conrad A, Müller A, Doberenz S, Kim S, Meuret AE, Wollburg E, Roth WT.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, and the Veterans Affairs Health Care System, Palo Alto, CA, USA.

Stressed and tense individuals often are recommended to change the way they breathe. However, psychophysiological effects of breathing instructions on respiration are rarely measured. We tested the immediate effects of short and simple breathing instructions in 13 people seeking treatment for panic disorder, 15 people complaining of daily tension, and 15 controls. Participants underwent a 3-hour laboratory session during which instructions to direct attention to breathing and anti-hyperventilation instructions to breathe more slowly, shallowly, or both were given. Respiratory, cardiac, and electrodermal measures were recorded. The anti-hyperventilation instructions failed to raise end-tidal pCO(2) above initial baseline levels for any of the groups because changes in respiratory rate were compensated for by changes in tidal volume and vice versa. Paying attention to breathing significantly reduced respiratory rate and decreased tidal volume instability compared to the other instructions. Shallow breathing made all groups more anxious than did other instructions. Heart rate and skin conductance were not differentially affected by instructions. We conclude that simple and short instructions to alter breathing do not change respiratory or autonomic measures in the direction of relaxation, except for attention to breathing, which increases respiratory stability. To understand the results of breathing instructions for stress and anxiety management, respiration needs to be monitored physiologically.

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J Clin Psychopharmacol. 2007 Jun;27(3):263-72.
The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence.
Mula M, Pini S, Cassano GB.
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Pisa, Italy. marcomula@yahoo.it

Antiepileptic drugs (AEDs) have been successfully used in the treatment of mood disturbances, leading clinicians and researchers to investigate their use in other psychiatric disorders. This article reviews the literature about the potential efficacy of AEDs in anxiety disorders. An updated MEDLINE search (January 1970 to September 2006) using the terms "panic disorder," "agoraphobia," "posttraumatic stress disorder," "obsessive-compulsive disorder," "generalized anxiety disorder," "social phobia," "phobia," "carbamazepine," "phenobarbital," "phenytoin," "valproate," "lamotrigine," "topiramate," "vigabatrin," "tiagabine," "gabapentin," "levetiracetam," and "pregabalin" showed more than 70 articles and 38 published studies. Only articles published in English were reviewed. We have assigned level 1 of evidence to meta-analysis and replicated randomized controlled trials, level 2 to at least 1 randomized controlled trial, level 3 to uncontrolled trials with 10 or more subjects, and level 4 to anecdotal case reports. The strongest evidence has been demonstrated for pregabalin in social phobia and generalized anxiety disorder, lamotrigine in posttraumatic stress disorder, and gabapentin in social anxiety. The available data about gabapentin in panic disorder are somewhat mixed, and more definitive conclusion would require additional studies. This review suggests that AEDs can be an alternative treatment in some anxiety disorders. Further investigation is needed to determine in what circumstances they should be used in individuals who are partially responsive or nonresponsive to conventional therapy.

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BMC Psychiatry. 2007 May 14;7:18.
Combination of psychotherapy and benzodiazepines versus either therapy alone for panic disorder: a systematic review.
Watanabe N, Churchill R, Furukawa TA.
Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. noriow@med.nagoya-cu.ac.jp

BACKGROUND: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone. METHODS: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials. RESULTS: Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6-12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment.One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials. CONCLUSION: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects.

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J Clin Psychol. 2007 Apr;63(4):409-16.
Cognitive-Behavioral group treatment for panic disorder with agoraphobia.
Galassi F, Quercioli S, Charismas D, Niccolai V, Barciulli E.
University of Florence.

Cognitive-behavioral therapy (CBT) is well documented in the treatment of panic disorder with or without agoraphobia; however, little is known about the efficacy of group treatment. The purpose of this open study is to investigate the benefits of a combination of the major cognitive and behavioral techniques used in the several specific versions of CBT thus far developed, in a psychotherapeutic group approach for panic and agoraphobia. Seventy-six outpatients meeting the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R; American Psychiatric Association, 1987) criteria for panic disorder with or without agoraphobia were included in the study. The treatment consisted of 14 weekly 2-hr group sessions and included: (a) an educational component, (b) interoceptive exposure, (c) cognitive restructuring, (d) problem solving, and (e) in vivo exposure. Patients achieved significant treatment gains on all dimensions assessed with a high rate of panic remission and significant improvement in the associated symptoms. Furthermore, these gains were maintained at 6-months' follow-up. Our results suggest the feasibility of this combination of cognitive and behavioral techniques. The findings raise questions about the specificity and the impact of each technique. (c) 2007 Wiley Periodicals, Inc. J Clin Psychol 63: 409-416, 2007.

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Nervenarzt. 2007 Mar;78(3):349-360.
[Anxiety disorders : Causes, clinical picture and treatment.]
[Article in German]
Zwanzger P, Deckert J.
Spezialambulanz fur Angsterkrankungen und Forschungsbereich Angst, Klinik fur Psychiatrie und Psychotherapie, Westfalische Wilhelms-Universitat Munster, Albert-Schweitzer-Strasse 11, 48149, Munster, Deutschland, Zwanzger@ukmuenster.de.

Anxiety disorders are among the most frequent mental disorders together with affective disorders with a lifetime prevalence of 18%. The pathogenesis of these disorders is complex and includes biological and psychosocial factors. Modern diagnostic classification systems (ICD-10, DSM-IV) differentiate between panic disorder with or without agoraphobia, generalized anxiety disorder, social phobia and specific phobia. Recommended treatment approaches include psychotherapy as well as pharmacotherapy, which have to be preceded by an empathic psychoeducation. Today, cognitive behavioural psychotherapy and modern antidepressants such as selective serotonin reuptake inhibitors represent the first-line therapy of most anxiety disorders. This review gives an overview of pathogenesis, clinical presentation and current treatment standards.

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Expert Rev Neurother. 2007 Feb;7(2):107-20.
Paroxetine: current status in psychiatry.
Pae CU, Patkar AA.
Department of Psychiatry & Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA. pae@catholic.ac.kr

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anxiolytic properties. It is commercially available in both an immediate-release (paroxetine) and a controlled-release formulation (paroxetine CR). The latter product was developed to improve gastrointestinal tolerability. Paroxetine is the most potent inhibitor of the reuptake of serotonin among the available SSRIs. It has approved indications for the treatment of major depression, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, post-traumatic stress disorder and social phobia in adults. Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults. While the overall efficacy of paroxetine appears to be comparable with other SSRIs in the treatment of major depression, it is approved for use in a wider variety of anxiety disorders than any other antidepressant. Long-term data suggest that paroxetine is effective in preventing relapse or recurrence of depression for up to 1 year. Limited data show that paroxetine maintains a therapeutic response over 1 year in obsessive-compulsive disorder and up to 6 months in panic disorder. The side-effect profile of paroxetine is largely similar to that of the other SSRIs, although paroxetine tends to be more sedating and constipating in some patients, perhaps due to its anticholinergic activity. The potential for discontinuation syndrome and weight gain appears to be slightly higher with paroxetine than with other SSRIs. This review focuses on the immediate release and controlled-release formulations of paroxetine. It summarizes the efficacy and tolerability data for both formulations, with a particular emphasis on paroxetine CR which was introduced in 2002. It also discusses emerging evidence in other clinical areas and recent data that have led to modifications in the safety profile of paroxetine.

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Am J Psychiatry. 2007 Feb;164(2):265-72.
A randomized controlled clinical trial of psychoanalytic psychotherapy for panic disorder.
Milrod B, Leon AC, Busch F, Rudden M, Schwalberg M, Clarkin J, Aronson A, Singer M, Turchin W, Klass ET, Graf E, Teres JJ, Shear MK.
Weill Medical College of Cornell University, 525 East 68th St., New York, NY 10021, USA. bmilrod@med.cornell.edu

OBJECTIVE: The purpose of this study was to determine the efficacy of panic-focused psychodynamic psychotherapy relative to applied relaxation training, a credible psychotherapy comparison condition. Despite the widespread clinical use of psychodynamic psychotherapies, randomized controlled clinical trials evaluating such psychotherapies for axis I disorders have lagged. To the authors' knowledge, this is the first efficacy randomized controlled clinical trial of panic-focused psychodynamic psychotherapy, a manualized psychoanalytical psychotherapy for patients with DSM-IV panic disorder. METHOD: This was a randomized controlled clinical trial of subjects with primary DSM-IV panic disorder. Participants were recruited over 5 years in the New York City metropolitan area. Subjects were 49 adults ages 18-55 with primary DSM-IV panic disorder. All subjects received assigned treatment, panic-focused psychodynamic psychotherapy or applied relaxation training in twice-weekly sessions for 12 weeks. The Panic Disorder Severity Scale, rated by blinded independent evaluators, was the primary outcome measure. RESULTS: Subjects in panic-focused psychodynamic psychotherapy had significantly greater reduction in severity of panic symptoms. Furthermore, those receiving panic-focused psychodynamic psychotherapy were significantly more likely to respond at treatment termination (73% versus 39%), using the Multicenter Panic Disorder Study response criteria. The secondary outcome, change in psychosocial functioning, mirrored these results. CONCLUSIONS: Despite the small cohort size of this trial, it has demonstrated preliminary efficacy of panic-focused psychodynamic psychotherapy for panic disorder.

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Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004518.
Passiflora for anxiety disorder.
Miyasaka L, Atallah A, Soares B.

BACKGROUND: Anxiety is a very common mental health problem in the general population and in the primary care setting. Herbal medicines are popularly used worldwide and could be an option for treating anxiety if shown to be effective and safe. Passiflora (passionflower extract) is one of these compounds. OBJECTIVES: To investigate the effectiveness and safety of passiflora for treating any anxiety disorder. SEARCH STRATEGY: The following sources were used: electronic databases: Cochrane Collaboration Depression, Anxiety and Neurosis Cochrane Controlled Trials Register (CCDANCTR-Studies), Medline and Lilacs; Cross-checking references; contact with authors of included studies and manufacturers of passiflora. SELECTION CRITERIA: Relevant randomised and quasi-randomised controlled trials of passiflora using 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 mental health disorder in which anxiety is a core symptom (panic disorder, obsessive compulsive disorder, social phobia, agoraphobia, other types of phobia, postraumatic stress disorder). Effectiveness was measured using clinical outcome measures such as Hamilton Anxiety Scale (HAM-A) and other scales for anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials found through the search strategy, extracted data, performed the trial quality analyses and entered data. Where any disagreements occured, the third reviewer was consulted. Methodological quality of the trials included in this review was assessed using the criteria described in the Cochrane Handbook. For dichotomous outcomes, relative risk with 95% confidence intervals (CI) were calculated, and for continuous outcomes, weighted mean difference with 95%CI was used. MAIN RESULTS: Two studies, with a total of 198 participants, were eligible for inclusion in this review. Based on one study, a lack of difference in the efficacy of benzodiazepines and passiflora was indicated. Dropout rates were similar between the two interventions. Although the findings from one study suggested an improvement in job performance in favour of passiflora (post-hoc outcome) and one study showed a lower rate of drowsiness as a side effect with passiflora as compared with mexazolam, neither of these findings reached statistical significance. AUTHORS' CONCLUSIONS: RCTs examining the effectiveness of passiflora for anxiety are too few in number to permit any conclusions to be drawn. RCTs with larger samples that compare the effectiveness of passiflora with placebo and other types of medication, including antidepressants, are needed.

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Behav Res Ther. 2007 Jan 28; [Epub ahead of print]
Implications of naturalistic use of pharmacotherapy in CBT treatment for panic disorder.
Arch JJ, Craske MG.
Department of Psychology, Franz Hall, University of California, Los Angeles, CA 90095-1563, USA.

This study examined naturalistic medication use and cognitive behavioral therapy (CBT) treatment outcomes in 105 patients meeting DSM-IV criteria for panic disorder (PD), assessed by structured clinical interview. The association between pre- and post-treatment use of SSRIs, benzodiazepines (BZs), and any anti-anxiety or anti-depressant (A/D) medication were investigated for three indicators of treatment outcome (PD severity, presence of agoraphobia (AG), anxiety sensitivity) at post-treatment and 6-month follow-up. Controlling for pre-treatment severity, pre-treatment SSRI use was associated with worse outcomes for AG (p=.04) and anxiety sensitivity (p=.047); post-treatment SSRI use was associated with delayed improvements in PD severity (p=.05). Pre-treatment use of A/D was associated with poorer PD severity outcomes (p=.04). Post-treatment use of A/D was associated with higher anxiety sensitivity scores across post-treatment and 6-month follow-up (p=.03). BZ use was not associated with significantly worse outcomes. However, there was a decrease in the number of patients using BZs from pre-treatment to post-treatment (p=.06) and follow-up (p=.006). In conclusion, controlling for pre-treatment severity, pre- and post-treatment use of SSRIs and A/D was associated with poorer outcomes, particularly for PD severity and anxiety sensitivity.

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J Clin Psychiatry. 2007 Jan;68(1):58-68.
Relapse prevention of panic disorder in adult outpatient responders to treatment with venlafaxine extended release.
Ferguson JM, Khan A, Mangano R, Entsuah R, Tzanis E.
University of Utah School of Medicine, Psychiatry, Salt Lake City, UT 84103, USA. Drjimferguson@yahoo.com

OBJECTIVE: To compare the long-term efficacy of venlafaxine extended release (ER) with placebo in preventing panic disorder relapse in out-patient treatment responders. METHOD: Outpatients aged > or = 18 years who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for panic disorder with or without agoraphobia for at least the previous 3 months, with > or = 6 full symptom panic attacks in the 2 weeks prior to screening and > or = 3 in the 2 weeks before baseline and a Clinical Global Impressions-Severity of Illness rating > or = 4 at screen were eligible to participate. Outpatients received flexible-dose (75-225 mg/day) venla-faxine ER for 12 weeks. Treatment responders were randomly assigned to venlafaxine ER or placebo for 26 weeks. Criteria for response were < or = 1 panic attack per week during the last 2 weeks of open-label treatment and a Clinical Global Impressions-Improvement score of 1 or 2. The primary endpoint, time to relapse during double-blind treatment, defined as > or = 2 full symptom panic attacks per week for 2 consecutive weeks or discontinuation due to loss of effectiveness, was evaluated using Kaplan-Meier survival analysis. The study was conducted between December 2001 and August 2003. RESULTS: The intent-to-treat population had 291 patients in the open-label phase and 169 in the double-blind phase (placebo, N = 80; venlafaxine ER, N = 89; mean daily dose 165-171 mg). Time to relapse was significantly longer with venlafaxine ER than placebo (p < .001). All secondary measures of panic attack treatment efficacy, quality of life, and disability were significantly better with venlafaxine ER than placebo (p < or = .005). CONCLUSION: Venlafaxine ER was safe, well tolerated, and effective in preventing relapse in outpatients with panic disorder.

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Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004364.
Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia.
Furukawa T, Watanabe N, Churchill R.

BACKGROUND: Panic disorder can be treated with pharmacotherapy, psychotherapy or in combination, but the relative merits of combined therapy have not been well established. OBJECTIVES: To review evidence concerning short- and long-term advantages and disadvantages of combined psychotherapy plus antidepressant treatment for panic disorder with or without agoraphobia, in comparison with either therapy alone. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) were searched on 11/10/2005, together with a complementary search of the Cochrane Central Register of Controlled Trials and MEDLINE, using the keywords antidepressant and panic. A reference search, SciSearch and personal contact with experts were carried out. SELECTION CRITERIA: Two independent review authors identified randomised controlled trials comparing the combined therapy against either of the monotherapies among adult patients with panic disorder with or without agoraphobia. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data using predefined data formats, including study quality indicators. The primary outcome was relative risk (RR) of "response" i.e. substantial overall improvement from baseline as defined by the original investigators. Secondary outcomes included standardised weighted mean differences in global severity, panic attack frequency, phobic avoidance, general anxiety, depression and social functioning and relative risks of overall dropouts and dropouts due to side effects. MAIN RESULTS: We identified 23 randomised comparisons (representing 21 trials, 1709 patients), 21 of which involved behaviour or cognitive-behaviour therapies. In the acute phase treatment, the combined therapy was superior to antidepressant pharmacotherapy (RR 1.24, 95% confidence interval (CI) 1.02 to 1.52) or psychotherapy (RR 1.17, 95% CI 1.05 to 1.31). The combined therapy produced more dropouts due to side effects than psychotherapy (number needed to harm (NNH) around 26). After the acute phase treatment, as long as the drug was continued, the superiority of the combination over either monotherapy appeared to persist. After termination of the acute phase and continuation treatment, the combined therapy was more effective than pharmacotherapy alone (RR 1.61, 95% CI 1.23 to 2.11) and was as effective as psychotherapy (RR 0.96, 95% CI 0.79 to 1.16). AUTHORS' CONCLUSIONS: Either combined therapy or psychotherapy alone may be chosen as first line treatment for panic disorder with or without agoraphobia, depending on patient preference.
 

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