Adjunctive Glycine in the Treatment of Obsessive-compulsive Disorder in Adults

Background: Recent preclinical findings, case reports and non-blinded studies have suggested that glutamatergic interventions may be efficacious for Obsessive-Compulsive Disorder (OCD).

Methods: We enrolled 24 adult outpatients with OCD on stabilized treatment regimens in a double-blind trial of adjunctive glycine, an NMDA glutamate receptor agonist. Participants were randomly assigned 1:1 to either placebo or glycine titrated to 60g/day, with follow-up visits scheduled at 4, 8 and 12 weeks. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the principal outcome measure.

Results: Regimen non-adherence, principally related to complaints about the taste and/or nausea, resulted in only 14 individuals who were evaluable by predetermined criteria. Those receiving glycine (n=5) experienced a mean decrease of 6.04 points in Y-BOCS score, compared with a 1.00 point decrease for those receiving placebo (n=9). Using a hierarchical linear model, compared with placebo, individuals who received glycine had an average 0.82 decrease in Y-BOCS score for each week they remained in the study, not quite reaching statistical significance (p=0.053). Two of those receiving glycine were responders, versus none receiving placebo (p=0.11, ns, Fisher exact). Despite the dropouts, two participants were known to have subsequently continued taking glycine through their regular treating psychiatrist for over a year.

Conclusions: The glycine condition approached efficacy for treatment of OCD in this study, with the high dropout rate related to problems with palatability and small sample size the principal caveats. This may indicate a new strategy for treatment of OCD, although confirmatory studies are clearly needed. (ClinicalTrials.gov NCT00405535.).