Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study

J Clin Psychopharmacol. 2011 Jun;31(3):369-74. doi: 10.1097/JCP.0b013e3182189878.

Abstract

Background: Several lines of evidence implicate glutamatergic neurotransmission in the pathophysiology of obsessive compulsive disorder (OCD). Sarcosine is an endogenous antagonist of glycine transporter-1. By blocking glycine uptake, sarcosine may increase the availability of synaptic glycine and enhance N-methyl-d-aspartate (NMDA) subtype glutamatergic neurotransmission. In this 10-week open-label trial, we examined the potential benefit of sarcosine treatment in OCD patients.

Method: Twenty-six outpatients with OCD and baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) scores higher than 16 were enrolled. Drug-naive subjects (group 1, n = 8) and those who had discontinued serotonin reuptake inhibitors for at least 8 weeks at study entry (group 2, n = 6) received sarcosine monotherapy. The other subjects (group 3, n = 12) received sarcosine as adjunctive treatment. A flexible dosage schedule of sarcosine 500 to 2000 mg/d was applied. The primary outcome measures were Y-BOCS and Hamilton Anxiety Inventory, rated at weeks 0, 2, 4, 6, 8, and 10. Results were analyzed by repeated-measures analysis of variance.

Results: Data of 25 subjects were eligible for analysis. The mean ± SD Y-BOCS scores decreased from 27.6 ± 5.8 to 22.7 ± 8.7, indicating a mean decrease of 19.8% ± 21.7% (P = 0.0035). Eight (32%) subjects were regarded as responders with greater than 35% reduction of Y-BOCS scores. Five of the responders achieved the good response early by week 4. Although not statistically significant, drug-naive (group 1) subjects had more profound and sustained improvement and more responders than the subjects who had received treatment before (groups 2 and 3). Sarcosine was tolerated well; only one subject withdrew owing to transient headache.

Conclusion: Sarcosine treatment can achieve a fast therapeutic effect in some OCD patients, particularly those who are treatment naive. The study supports the glycine transporter-1 as a novel target for developing new OCD treatment. Large-series placebo-controlled, double-blind studies are recommended.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drug Therapy, Combination / statistics & numerical data
  • Female
  • Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Humans
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / drug therapy*
  • Psychiatric Status Rating Scales
  • Psychotropic Drugs / administration & dosage
  • Psychotropic Drugs / therapeutic use*
  • Sarcosine / administration & dosage
  • Sarcosine / therapeutic use*

Substances

  • Glycine Plasma Membrane Transport Proteins
  • Psychotropic Drugs
  • SLC6A9 protein, human
  • Sarcosine