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Exposure and response prevention is the most effective treatment for obsessive-compulsive disorder (OCD). However, at least one fourth of patients avoid or drop out of treatment early on because it is anxiety-provoking and requires considerable effort. Synergy between SSRIs and behavioral therapy for OCD has not been reported. A possible enhancer of early response to behavioral therapy might be D-cycloserine (DCS), an antibiotic used to treat tuberculosis that boosts glutamate signaling by acting on the glycine site of the N-methyl-d-aspartate (NMDA) receptor.
Researchers randomized 32 patients with OCD to receive DCS (125 mg) or placebo 2 hours before each of 10 sessions of standard behavioral therapy. The sessions involved increasingly upsetting, ritual-evoking stimuli (e.g., touching a toilet seat). Once therapy reduced distress from a stimulus by 50%, the next stimulus was introduced.
By the fourth session, but not at the end of treatment, significantly greater reduction in subjective distress in response to the stimuli was associated with DCS than with placebo. Treatment groups had equivalent reductions in OCD symptoms at the end of treatment and 3 months later. Fewer DCS recipients than placebo recipients dropped out (6% vs. 35%).
Kushner MG et al. D-cycloserine augmented exposure therapy for obsessive-compulsive disorder. Biol Psychiatry 2007 Oct 15; 62:835.
Krystal JH. Neuroplasticity as a target for the pharmacotherapy of psychiatric disorders: New opportunities for synergy with psychotherapy. Biol Psychiatry 2007 Oct 15; 62:833.
Comment
Behavioral therapy promotes extinction of conditioned fear by repeatedly pairing the feared stimulus with relaxation and mastery. A commentator theorizes that enhanced glutamate neurotransmission facilitates the neuroplasticity that is necessary to reorder connections between perception and the fear response. If this finding is confirmed, clinicians might use cycloserine to promote faster reduction of distress, motivating patients to remain in therapy until it becomes effective. Patients who are leery of starting or continuing behavioral therapy may be candidates for early use of DCS — once compulsions decrease, the medication appears to have no further benefit.