D-cycloserine in the treatment of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a common and serious psychiatric illness. Exposure therapy is a type of cognitive behavioral therapy that is considered a first-line treatment option for PTSD. D-cycloserine (DCS) enhances fear extinction/exposure therapy in patients with various anxiety disorders, presumably via its N-methyl-D-aspartate receptor partial agonist effects. The aim of this paper is to review the published literature regarding the efficacy of DCS in the treatment of PTSD.

A literature search for placebo-controlled trials assessing the use of DCS as the primary study drug in PTSD was conducted for trials published before June 2015 using PubMed, Ovid International Pharmaceutical Abstracts, and www.clinicaltrials.gov. The search terms were variations of "cycloserine" and "posttraumatic stress disorder."

Seven clinical trials were analyzed, including 2 trials comparing DCS with placebo as add-on treatment to ongoing stable pharmacotherapy and 5 trials that compared DCS with placebo given prior to exposure therapy. D-cycloserine as adjunctive therapy showed no benefit in 1 trial and limited benefit in the other. As an enhancement of exposure therapy, DCS showed beneficial effects in 1 trial, detrimental effects in 1 trial, and inconclusive effects in 3 trials.

Current literature does not adequately support the use of DCS as adjunctive therapy without psychotherapy, but limitations of the 2 studies that exist make firm conclusions unfeasible. D-cycloserine might have a role in augmentation of exposure therapy. Future studies should consider receptor selectivity, administration time with respect to peak cerebrospinal fluid concentrations, number of exposure therapy sessions, and dose.