d-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants

Abstract

IMPORTANCE It is unclear whether D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). OBJECTIVES To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS. DESIGN, SETTING, AND PARTICIPANTS A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population. INTERVENTIONS All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks. MAIN OUTCOMES AND MEASURES Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS. RESULTS In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = −1.08; Z = −2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t 62 = −3.00; P = .004; and t 61 = −3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups). CONCLUSIONS AND RELEVANCE The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.

Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjustedd-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder

“…Preliminary data among youth 29,30 and adults 24 with OCD, a recent fully powered study 28 among adults with OCD not taking an antidepressant, and several studies 12–16 of non-OCD anxiety highlight the potential for D-cycloserine to safely augment CBT. However, we found no evidence in the present study that D-cycloserine augmentation of CBT was more effective than CBT monotherapy or that concomitant antidepressant medication adversely moderated outcomes.…”

“…D-cycloserine and matching pill placebo were encapsulated by a site-specific investigational pharmacy using the same procedures into 25 mg with identical placebo capsules and, consistent with other research, 12,15,24,28,29 were taken 1 hour before sessions 4 through 10 supervised by a research coordinator to ensure compliance. Two dosing levels were used, based on weight ranges, to ensure comparable levels (milligrams per kilogram).…”

“…No significant group Yale-Brown Obsessive Compulsive Scale score differences existed posttreatment ( d = −0.19) or in the rate of response. Andersson et al 28 found no main effect of 50 mg of D-cycloserine relative to placebo augmentation (n = 128) of 12 internet CBT sessions. Concomitant serotonin reuptake inhibitor medication moderated effects such that among patients randomized to D-cycloserine augmentation those who were not taking a serotonin reuptake inhibitor were significantly more likely to achieve remission at follow-up (60% vs 24%).…”

“…More recent evidence suggests that beneficial effects may be adversely moderated by concomitant antidepressant medication. 28 Accordingly, we evaluated in a double-blind, placebo-controlled design whether D-cycloserine augments CBT efficacy to a greater extent than placebo. We hypothesized that D-cycloserine vs placebo augmentation would be associated with greater overall response and a faster rate of treatment response.…”

Dose timing of d -cycloserine to augment cognitive behavioral therapy for social anxiety: Study design and rationale

“…There is some evidence to suggest that antidepressants interact with DSC to block its augmentation effect on fear extinction. 47 Therefore, consistent with our earlier trial 12 we decided to exclude participants with concurrent psychotropic medication use. Our experience with this earlier trial indicates that this exclusion criterion is unlikely to negatively affect recruitment or generalizability of the findings.…”