Efficacy of d-cycloserine for enhancing response to cognitive-behavior therapy for panic disorder.
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.


METHODS
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.
Otto
Michael W
MW
Center for Anxiety and Related Disorders at Boston University, Massachusetts 02215, USA. mwotto@bu.edu
Tolin
David F
DF
Simon
Naomi M
NM
Pearlson
Godfrey D
GD
Basden
Shawnee
S
Meunier
Suzanne A
SA
Hofmann
Stefan G
SG
Eisenmenger
Katherine
K
Krystal
John H
JH
Pollack
Mark H
MH
D000328:Adult; D000704:Analysis of Variance; D000963:Antimetabolites / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003523:Cycloserine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000628:therapy*; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D055815:Young Adult
D000963:Antimetabolites; D003523:Cycloserine