10006247 J Clin Psychiatry / Document Archive

Psychiatrist.com Home    Keyword Search

Close [X]

Search Our Sites

Enter search terms below (keywords, titles, authors, or subjects). Then select a category to search and press the Search button. All words are assumed to be required. To search for an exact phrase, put it in quotes. To exclude a term, precede it with a minus sign (-).

Keyword search:

Choose a category:

Choosing the appropriate category will greatly improve your chances of finding the best match.

All files at our sites: J Clin Psychiatry, Primary Care Companion, CME Institute, and MedFair

Search materials from our journals:

Abstracts from The Journal of Clinical Psychiatry, 1996–present, both regular issues and supplements

PDFs of the full text of The Journal of Clinical Psychiatry, 1996–present, both regular issues and supplements (Net Society Platinum [paid subscribers])

PDFs of the full text of The Primary Care Companion to The Journal of Clinical Psychiatry, 1999–present

Search CME offerings:

CME Institute, including CME from journals , supplements, and Web activities for instant CME credit (Net Society Gold [registered users]); also includes information about our CME program

CME activities from regular issues of The Journal of Clinical Psychiatry (Net Society Gold [registered users])

CME Supplements from The Journal of Clinical Psychiatry (Net Society Gold [registered users])


The article you requested is

Next-Step Strategies for Panic Disorder Refractory to Initial Pharmacotherapy: A 3-Phase Randomized Clinical Trial

J Clin Psychiatry 2009;70(11):1563-1570
Copyright 2009 Physicians Postgraduate Press, Inc.

To view this item, select one of the options below.

    1. Purchase this PDF for $40
      If you are not a paid subscriber, you may purchase the PDF.
      (You'll need the free Adobe Acrobat Reader.)
    2. Subscribe
      Receive immediate full-text access to JCP. You can subscribe to JCP print + online for $166 individual.
      JCP's 75th AnniversaryCelebrate!
      Celebrate JCP's 75th Anniversary with a special online-only subscription price of $75.
    1. Activate
      If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
    2. Sign in
      As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
  1. Did you forget your password?

Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send an email


Background: More data are needed to guide next-step interventions for panic disorder refractory to initial intervention.

Method: This 24-week randomized clinical trial (RCT) enrolled 46 patients with DSM-IV–defined panic disorder from November 2000 to April 2005 and consisted of 3 phases. Patients who failed to meet remission criteria were eligible for randomization in the next treatment phase. Phase 1 was a 6-week lead-in with open-label sertraline flexibly dosed to 100 mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 was a 6-week double-blind RCT of (1) increased-dose selective serotonin reuptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 was a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to “medication optimization” with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent-to-treat sample in each phase.

Results: In phase 1, 20.5% (8/39) of the patients achieved remission, and only baseline severity predicted endpoint PDSS score (β [SE]=1.04 [0.15], t=6.76, P<.001). In phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n=2] vs increased dose 9% [n=1]: Fisher exact test P=NS). In phase 3, remission was minimal (medication optimization=11% [n=1]; CBT=10% [n=1]), with a lack of group difference in PDSS score reduction (t17=0.51, P>.60) consistent with a small effect size (d=0.24).

Conclusions: Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in nonremitted panic after 12 weeks of an SSRI did not differ, suggesting that both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest that better predictors of response to specific treatments over time and additional interventions are needed.

Trial Registration: clinicaltrials.gov Identifier: NCT00118417

Submitted: June 20, 2008; accepted October 9, 2008.

Online ahead of print: October 6, 2009.

Corresponding author: Naomi M. Simon, MD, MSc, Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Simches Research Building, 2nd Floor, 185 Cambridge St, Boston, MA 02114 (nsimon@partners.org).