Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder

Abstract

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 triplemasked 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 (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 (continued) Key Points Question Does D-cycloserine potentiate the effect of concentrated exposure and response prevention in difficult-to-treat obsessive-compulsive disorder? Findings In this randomized clinical trial of 163 participants, D-cycloserine did not significantly affect treatment outcomes. Most patients responded to the concentrated exposure and response prevention treatme...

Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review

“…A meta-analysis of these three studies found small, nonsignificant positive effects of riluzole on obsessive-compulsive symptoms 39 . Other substances such as glycine, an NMDAR co-agonist, and D-cycloserine, a partial co-agonist at the glycine site of the NDMAR, have also been tested for treating OCD, with the latter producing negative results 40–42 and glycine showing a trend toward therapeutic effects 43 . Bitopertin is a glycine reuptake inhibitor studied mainly for negative symptoms of schizophrenia.…”

Treatment Adherence as Predictor of Outcome in Concentrated Exposure Treatment for Obsessive-Compulsive Disorder

“…Furthermore, the sample size limited the number of variables that could be included in the regression analyses. It is also a limitation that the study did not include patients that had been previously treated with EX/RP, because there was an ongoing parallel study for difficult-to-treat OCD-patients ( 51 ). Therefore, future studies should investigate the role of adherence using larger samples and in patients that have relapsed or not responded to previous treatments.…”

Efficacy of D‐cycloserine augmented brief intensive cognitive‐behavioural therapy for paediatric obsessive‐compulsive disorder: A randomised clinical trial

“…In a preliminary randomised controlled trial (RCT), Farrell et al (2013) reported significantly greater improvements in OCD symptoms for difficult-to-treat children and adolescents with OCD (n = 17) who received DCS augmented ERP relative to placebo (PBO) from posttreatment to 1-month follow-up. In contrast however, a large RCT (n = 163) of difficult-to-treat adults with OCD (Kvale et al, 2020) did not demonstrate overall benefits for DCS augmented intensive ERP (two doses over 2 consecutive days), despite earlier pilot RCTs with adults reporting significant benefits for DCS after only a few sessions of ERP (Kushner et al, 2007;Wilhelm et al, 2008). In a large RCT of youth, Storch et al (2016) (n = 142) found no overall benefit for weight-adjusted DCS augmented CBT relative to placebo on OCD severity following 10 sessions of CBT, 7 of which were augmented with DCS/PBO.…”