Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder

Michael W. Otto, David F. Tolin, Naomi M. Simon, Godfrey D. Pearlson, Shawnee Basden, Suzanne A. Meunier, Stefan G. Hofmann, Katherine Eisenmenger, John H. Krystal, Mark H. Pollack

Research output: Contribution to journalArticlepeer-review

206 Scopus citations


Background: Traditional combination strategies of cognitive-behavior therapy plus pharmacotherapy have met with disappointing results for anxiety disorders. Enhancement of cognitive-behavior therapy with d-cycloserine (DCS) pharmacotherapy represents a novel strategy for improving therapeutic learning from cognitive-behavior therapy that remains untested in panic disorder. Method: This is a randomized, double-blind, placebo-controlled augmentation trial examining the addition of isolated doses of 50 mg d-cycloserine or pill placebo to brief exposure-based cognitive-behavior therapy. Randomized participants were 31 outpatients meeting DSM-IV criteria for panic disorder with or without agoraphobia, who were offered five sessions of manualized cognitive-behavior therapy emphasizing exposure to feared internal sensations (interoceptive exposure) but also including informational, cognitive, and situational exposure interventions. Doses of study drug were administered 1 hour before cognitive-behavior therapy sessions 3 to 5. The primary outcome measures were the Panic Disorder Severity Scale (PDSS) and Clinicians' Global Impressions of Severity. Results: Results indicated large effect sizes for the additive benefit of d-cycloserine augmentation of cognitive-behavior therapy for panic disorder. At posttreatment and 1 month follow-up, participants who received d-cycloserine versus placebo had better outcomes on the PDSS and global severity of disorder and were significantly more likely to have achieved clinically significant change status (77% vs. 33%). There were no significant adverse effects associated with DCS administration. Conclusions: This pilot study extends support for the role of d-cycloserine in enhancing therapeutic learning from exposure-based cognitive-behavior therapy and is the first to do so in a protocol emphasizing exposure to feared internal sensations of anxiety in panic disorder.

Original languageEnglish (US)
Pages (from-to)365-370
Number of pages6
JournalBiological psychiatry
Issue number4
StatePublished - Feb 15 2010
Externally publishedYes


  • Cognitive-behavior therapy
  • d-cycloserine
  • panic disorder

ASJC Scopus subject areas

  • Biological Psychiatry


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