D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial.
Viewing post-traumatic stress disorder (PTSD) as a disorder of emotional learning, this study used a cognitive enhancer synergistically with virtual reality exposure (VRE) therapy for the treatment of PTSD. The main objective was to determine if a novel pharmacotherapy, D-cycloserine (DCS), enhanced the efficacy of the psychotherapy. Pre-clinical studies suggest that when fear extinction occurs during DCS administration, neuroplasticity may be enhanced. VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning, as sensory fear cues are standardized across patients. In a pilot randomized, double-blind, placebo-controlled trial, 100 mg of DCS or placebo was administered 90 min before each weekly VRE session, to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Beck Depression Inventory-II and the State-Trait Anger Expression Inventory-2. Assessments occurred at pre-treatment, following sessions 3, 6, 10, post-treatment, and at 6 months. The difference in CAPS between the VRE-DCS (n=13) and VRE-placebo (n=12) groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later (d=0.68 and d=1.13, respectively). A similar pattern was observed for depression, anger expression, and sleep. PTSD remission rates were significantly greater for the VRE-DCS group (46% vs 8% at post-treatment; 69% vs 17% at 6 months). Patients in the VRE-DCS group showed earlier and greater improvement in PTSD symptoms compared with the VRE-placebo group. These results suggest a promising new treatment for PTSD.
1] Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA [2] NewYork-Presbyterian Hospital, New York, NY, USA.
JoAnn
J
Difede
1] Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA [2] NewYork-Presbyterian Hospital, New York, NY, USA.
Judith
J
Cukor
Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
Katarzyna
K
Wyka
1] Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA [2] NewYork-Presbyterian Hospital, New York, NY, USA.
Megan
M
Olden
Department of Mechanical Engineering, Human Interface Technology Laboratory, and Human Photonics Laboratory, University of Washington, Seattle, WA, USA.
Hunter
H
Hoffman
1] Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA [2] NewYork-Presbyterian Hospital, New York, NY, USA.
Francis S
FS
Lee
1] Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA [2] NewYork-Presbyterian Hospital, New York, NY, USA.
Margaret
M
Altemus
D000328:Adult; D000368:Aged; D000786:Anger / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002908:Chronic Disease; D003523:Cycloserine / Q000097:blood / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy / Q000628:therapy; D004311:Double-Blind Method; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005260:Female; D006801:Humans; D007171:Implosive Therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000097:blood / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D011619:Psychotropic Drugs; D003523:Cycloserine