Subject:
PTSD

Short Description:
Study Suggests DCS Not Effective in PTSD Treatment

Background:

Exposure therapy is a cognitive behavioral strategy that serves as a core treatment for anxiety disorders. Animal and human studies alike have supported the use of D-cycloserine (DCS) as an agent to augment the effectiveness of exposure therapy in specific phobia, social phobia, panic disorder, and obsessive-compulsive disorder. D-cycloserine, also known as Seromycin, is an antituberculosis drug that also acts as a partial agonist of the NMDA receptor. It is hypothesized that stimulation of NMDA receptors helps enable “extinction learning,” or the remodeling of pathways in the amygdala to decrease conditioned fear responses.

A new study, however, finds that DCS does not improve treatment responses in patients undergoing prolonged exposure therapy for posttraumatic stress disorder, or PTSD. Sixty-seven patients with PTSD underwent a standardized program of up to 10 sessions of prolonged exposure therapy. Half (33) received 50 mg of D-cycloserine one hour before each exposure session while the others received placebo. Most of the patients completing the trial reported a decrease in symptoms as measured by the Post traumatic Stress Symptom Scale (PSS-SR). Patients taking DCS had higher response rates (odds ratio for response was 2.83, 95%CI=1.05–7.61), but statistical tests showed that this could not be attributed to DCS, probably because of differences in baseline severity between groups.

Patients were allowed to continue their other medications during the study, and the events underlying each patient’s PTSD varied from sexual assault to traffic accidents. Also, nearly one-third of the patients dropped out of the study. These factors might explain the lack of an obvious benefit of DCS. A subgroup analysis, however, showed that those patients who required the full 10 sessions of therapy were significantly more likely to benefit from DCS: mean PSS-SR scores decreased by 43.9% in those receiving DCS, vs only 7.8% in those receiving placebo (de Kleine RA et al, Biol Psychiatry 2012;71:962–968).

TCPR's Take:
DCS does not appear to enhance treatment response in patients undergoing exposure therapy for PTSD. There was some suggestion that it may help patients with serious symptoms who require longer treatment, compared with those who complete treatment earlier. But previous, smaller studies on DCS in exposure therapy for other anxiety disorders showed effects in just a few sessions, and another recent paper shows that patients undergoing short-term exposure for war-related PTSD actually did worse with DCS (Litz BT et al, J Psychiatr Res 2012:online ahead of print). Whether DCS has a place in treating PTSD is still not clear, but these studies suggest that it probably contributes little to a good, evidence-based modality like exposure therapy.