Feasibility, safety, and efficacy of the combination of D-serine and computerized cognitive retraining in schizophrenia: an international collaborative pilot study

Neuropsychopharmacology. 2013 Feb;38(3):492-503. doi: 10.1038/npp.2012.208. Epub 2012 Oct 24.


The combination of pharmacotherapy and cognitive retraining (CRT) for the cognitive deficits of schizophrenia may be more efficacious than either approach alone, but this has not yet been tested. This study evaluated the feasibility, safety, tolerability, and efficacy of 12 weeks of D-serine, combined with CRT in the treatment of cognitive deficits in schizophrenia at two academic sites in parallel, in India and the United States. In a randomized, partial double-blind, placebo-controlled, parallel-group design, 104 schizophrenia subjects (US site=22, Indian site=82) were randomized to: (1) D-serine (30 mg/kg)+CRT (5 h/week), (2) D-serine+control CRT, (3) CRT+placebo D-serine, and (4) placebo+control CRT. Completion rates were 84 and 100% in the Indian and US samples, respectively. On various outcome measures of safety and tolerability, the interventions were well tolerated. D-Serine and CRT did not show any significant effect on the Global Cognitive Index, although both interventions showed differential site effects on individual test performance. CRT resulted in a significant improvement in Verbal Working Memory, and a trend toward improvement in Attention/Vigilance. This is the first study to demonstrating the feasibility, safety, and tolerability of combination pharmacotherapy and CRT in a multicenter international clinical trial. These preliminary findings provide support for future studies using higher doses of D-serine that have been shown to be efficacious or other pharmacotherapies, along with the newer cognitive remediation strategies that are individualized and that target basic information processing.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Cognitive Behavioral Therapy / methods*
  • Combined Modality Therapy / methods
  • Computer-Assisted Instruction / methods*
  • Cooperative Behavior*
  • Double-Blind Method
  • Feasibility Studies
  • Female
  • Humans
  • Internationality
  • Male
  • Middle Aged
  • Pilot Projects
  • Schizophrenia / diagnosis
  • Schizophrenia / epidemiology
  • Schizophrenia / therapy*
  • Serine / administration & dosage*
  • Serine / adverse effects*
  • Treatment Outcome


  • Serine