title: Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taipei, Taiwan.
authors.forename: Po-Lun
authors.initials: PL
authors.lastname: Wu
authors.forename: Hwa-Sheng
authors.initials: HS
authors.lastname: Tang
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.forename: Chen-An
authors.initials: CA
authors.lastname: Tsai
authors.forename: Guochuan E
authors.initials: GE
authors.lastname: Tsai
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination / Q000706:statistics & numerical data; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000627:therapeutic use*; D012521:Sarcosine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; D011619:Psychotropic Drugs; C493268:SLC6A9 protein, human; D012521:Sarcosine