RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL THERAPY FOR PANIC DISORDER.
Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT.



We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects.



DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition.



Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation.
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
Michael W
MW
Otto
Department of Psychiatry, Rush University Medical Center, Chicago, Illinois.
Mark H
MH
Pollack
Department of Psychiatry, Rush University Medical Center, Chicago, Illinois.
Sheila M
SM
Dowd
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
Stefan G
SG
Hofmann
Institute of Living and Yale University School of Medicine, Hartford, Connecticut.
Godfrey
G
Pearlson
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
Kristin L
KL
Szuhany
Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Ralitza
R
Gueorguieva
Department of Psychiatry, Yale University School of Medicine and Yale-New Haven Hospital, New Haven, Connecticut.
John H
JH
Krystal
Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Naomi M
NM
Simon
Institute of Living and Yale University School of Medicine, Hartford, Connecticut.
David F
DF
Tolin
D000328:Adult; D000963:Antimetabolites / Q000494:pharmacology*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003131:Combined Modality Therapy; D003523:Cycloserine / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000188:drug therapy / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
D000963:Antimetabolites; D003523:Cycloserine
CBT; anxiety; clinical trials; panic attacks/agoraphobia; pharmacotherapy