, Volume 179, Issue 1, pp 144–150

A six-month, placebo-controlled trial of d-cycloserine co-administered with conventional antipsychotics in schizophrenia patients


    • Schizophrenia ProgramMassachusetts General Hospital
    • Freedom Trail Clinic
    • Harvard Medical School
  • Lawrence Herz
    • Bedford Veteran’s Affairs Medical CenterBoston University Medical School
  • Thomas Posever
    • Lemuel Shattuck HospitalTufts Medical School
  • Vivian Shih
    • Harvard Medical School
    • Pediatric Neurology ServiceMassachusetts General Hospital
  • Guochuan Tsai
    • McLean Hospital
  • David C. Henderson
    • Schizophrenia ProgramMassachusetts General Hospital
    • Harvard Medical School
  • Oliver Freudenreich
    • Schizophrenia ProgramMassachusetts General Hospital
    • Harvard Medical School
  • A. Eden Evins
    • Schizophrenia ProgramMassachusetts General Hospital
    • Harvard Medical School
  • Iftah Yovel
    • Schizophrenia ProgramMassachusetts General Hospital
    • Harvard Medical School
  • Hui Zhang
    • BiostatisticsMassachusetts General Hospital
  • David Schoenfeld
    • Harvard Medical School
    • BiostatisticsMassachusetts General Hospital
Original Investigation

DOI: 10.1007/s00213-004-2032-2

Cite this article as:
Goff, D.C., Herz, L., Posever, T. et al. Psychopharmacology (2005) 179: 144. doi:10.1007/s00213-004-2032-2



d-Cycloserine, a partial agonist at the glycine site of the N-methyl-d-aspartate receptor, has demonstrated inconsistent efficacy for negative and cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come from studies using d-cycloserine at a dose of 50 mg/day added to conventional antipsychotics in trials of 8 weeks duration or less.


To assess the efficacy for negative symptoms and cognitive impairment of d-cycloserine augmentation of conventional antipsychotics in a 6-month trial.


Fifty-five schizophrenia patients with prominent negative symptoms, treated with conventional antipsychotics, were randomly assigned to treatment with d-cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group design.


Twenty-six subjects completed the 6-month trial; drop-out rates did not differ between treatment groups. d-Cycloserine treatment did not differ from placebo treatment on any primary outcome measure at 8 or 24 weeks, including response of negative symptoms and performance on a cognitive battery. Serum d-cycloserine concentrations did not correlate with response of negative symptoms.


d-Cycloserine did not exhibit therapeutic effects in this trial, possibly reflecting the high drop-out rate, a narrow range of therapeutic serum concentrations, a modest magnitude of therapeutic effect for the selected outcome measures, or loss of efficacy over time. Because d-cycloserine is a partial agonist with relatively low affinity for the glycine site, the magnitude of potential therapeutic effect may be smaller than that achieved by the higher-affinity full agonists, glycine and d-serine.

Copyright information

© Springer-Verlag 2004