Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder: A Randomized Clinical Trial

Importance Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD. Objective To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD. Design, Setting, and Participants The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019. Interventions All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo. Main outcomes and Measures Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life. Results The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (allP  Conclusions and Relevance In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. Trial Registration ClinicalTrials.gov identifier:NCT02656342