Abstract
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. To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD. 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. 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. 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. 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 (all P < .001). However, there was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, -0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, -0.08 to 0.79), symptoms of depression and anxiety (eg, Patient Health Questionnaire-9 score among 250 mg group at 12-month follow-up: d = 0.30; 95% CI, -0.17 to 0.76; Generalized Anxiety Disorder-7 score among 100 mg group at 12-month follow-up: d = 0.27; 95% CI, -0.19 to 0.73), and well-being (250 mg group: d = 0.10; 95% CI, -0.42 to 0.63; 100 mg group: d = 0.34; 95% CI, -0.19 to 0.86). No serious adverse effects were reported. In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. ClinicalTrials.gov identifier: NCT02656342.
Highlights
Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder with a lifetime prevalence of 1% to 2%,1,2 often with onset in childhood.[3]
There was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, −0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, −0.08 to 0.79), symptoms of depression and anxiety
In this study, DCS did not potentiate Exposure and response prevention (ERP) treatment effect, but concentrated ERP treatment was associated with improvement
Summary
Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder with a lifetime prevalence of 1% to 2%,1,2 often with onset in childhood.[3]. The DCS studies included in meta-analyses are based on samples in which a treatment response would be expected for 62% to 68% of the sample.[4] Potentiation by DCS may be more evident in patients who have a documented history of being difficult to treat, ie, those who have not responded to ERP or who have responded but relapsed. These patients constitute the group most in need of alternative treatment approaches. One study[18] reported that DCS accelerated the rate of recovery in children with difficult-to-treat OCD, suggesting that DCS might be helpful for adults with difficult-to-treat OCD
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