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D-cycloserine may improve CBT outcomes for anxiety, OCD, PTSD

Recent findings suggested short-term efficacy of D-cycloserine augmentation of cognitive behavioral therapy for anxiety, obsessive-compulsive disorder, PTSD and phobia disorders.

“Anxiety, obsessive-compulsive, and posttraumatic stress disorders constitute the most prevalent group of mental disorders, collectively affecting up to 30% of individuals at some point in their lives,” David Mataix-Cols, PhD, of Karolinska Institutet, Stockholm, and colleagues wrote. “One promising strategy is the administration of D-cycloserine, a partial N-methyl-D-aspartate agonist that facilitates fear extinction in animals and reduces return of fear when given before or shortly after extinction training. Despite several initial trials showing promising results in humans with anxiety disorders, larger trials conducted within the past 5 years have produced mixed results.”

To assess efficacy of D-cycloserine in augmenting CBT for anxiety, OCD and PTSD and interactions between antidepressants and D-cycloserine, researchers conducted a systematic review and meta-analysis of 21 double-blind randomized clinical trials among 1,047 study participants. Analysis included studies that explored D-cycloserine as an augmentation strategy for exposure-based CBT among individuals with a specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, OCD or PTSD.

When controlling for antidepressant use, participants who received D-cycloserine exhibited greater improvement from pre- to posttreatment (mean difference = –3.62), but not from pre- to mid-treatment (mean difference = –1.66) or from pretreatment to follow-up (mean difference = –2.98).

Participants who received D-cycloserine had lower symptom severity at posttreatment and follow-up, compared with those who received placebo.

Analysis indicated antidepressants did not moderate D-cycloserine effects.

“We found evidence supporting the short-term superiority of [D-cycloserine] vs. placebo in the augmentation of exposure-based CBT for anxiety-related disorders and mixed support for the maintenance of these benefits at follow-up,” the researchers wrote. “While statistically significant, the effect sizes were small. Concomitant antidepressant medication did not significantly moderate the effects of [D-cycloserine]. None of the prespecified patient-level (eg, age and sex) or study-level (eg, primary diagnosis, number of exposure sessions, [D-cycloserine] dose, timing of administration, and number of [D-cycloserine] administrations) moderators were clearly associated with outcomes.” – by Amanda Oldt

Disclosure: All authors with the exception of Fernández de la Cruz, Frumento and Pérez-Vigil were investigators on at least one of the original randomized clinical trials that contributed data to the individual participant data and secured grant funding for these trials. Please see the study for a full list of relevant financial disclosures.