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One of the most effective treatments for post-traumatic stress disorder (PTSD) is prolonged exposure (PE) to reminders of the traumatic event. A co-agonist of the N-methyl-d-aspartate (NMDA) receptor, D-cycloserine (DCS), has been used to promote glutamate neurotransmission in the amygdala, which facilitates fear extinctions, a primary mechanism of PE (JW Psychiatry Jan 14 2008). In this Dutch, randomized, double-blind, placebo-controlled trial, researchers aimed to determine whether DCS (50 mg, taken 1 hour before each session) would improve PE in 75 patients with PTSD.
PE consisted of describing the traumatic event in the present tense and, as homework, listening to the recorded description. In the 67 patients who entered treatment, PE reduced PTSD ratings significantly from baseline. DCS and placebo improved ratings similarly. However, patients who needed a full course of PE because they did not improve quickly had a significantly better response to DCS than to placebo, and this benefit was maintained at 3 months after treatment.
de Kleine RA et al. A randomized placebo-controlled trial of D-cycloserine to enhance exposure therapy for posttraumatic stress disorder. Biol Psychiatry 2012 Jun 1; 71:962.
Comment
These results suggest that patients who improve rapidly with prolonged exposure will respond completely without additional help and do not need treatment augmentation, whereas those who need a full course of treatment have more persistent symptoms and respond better with activation of the NMDA receptor. Still, the D-cycloserine dose was quite a bit lower than that used in other studies; a higher dose might produce more robust responses in all patients. Patients with persistent PTSD might be considered for this strategy.