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

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Abstract

Rationale

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.

Objective

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

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

This study was supported by PHS RO1 MH54245, K24 MH02025, and P50 MH60450.

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Authors and Affiliations

  1. Schizophrenia Program, Massachusetts General Hospital, Boston, Mass., USA

    Donald C. Goff, David C. Henderson, Oliver Freudenreich, A. Eden Evins & Iftah Yovel

  2. Freedom Trail Clinic, 25 Staniford St, Boston, MA, 02114, USA

    Donald C. Goff

  3. Harvard Medical School, Boston, Mass., USA

    Donald C. Goff, Vivian Shih, David C. Henderson, Oliver Freudenreich, A. Eden Evins, Iftah Yovel & David Schoenfeld

  4. Bedford Veteran’s Affairs Medical Center, Boston University Medical School, Boston, Mass., USA

    Lawrence Herz

  5. Lemuel Shattuck Hospital, Tufts Medical School, Boston, Mass., USA

    Thomas Posever

  6. Pediatric Neurology Service, Massachusetts General Hospital, Boston, Mass., USA

    Vivian Shih

  7. McLean Hospital, Belmont, Mass., USA

    Guochuan Tsai

  8. Biostatistics, Massachusetts General Hospital, Boston, Mass., USA

    Hui Zhang & David Schoenfeld

Authors
  1. Donald C. Goff
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  2. Lawrence Herz
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  3. Thomas Posever
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  4. Vivian Shih
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  5. Guochuan Tsai
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  6. David C. Henderson
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  7. Oliver Freudenreich
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  8. A. Eden Evins
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  9. Iftah Yovel
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  10. Hui Zhang
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  11. David Schoenfeld
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Corresponding author

Correspondence to Donald C. Goff.

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Goff, D.C., Herz, L., Posever, T. et al. A six-month, placebo-controlled trial of d-cycloserine co-administered with conventional antipsychotics in schizophrenia patients. Psychopharmacology 179, 144–150 (2005). https://doi.org/10.1007/s00213-004-2032-2

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  • DOI: https://doi.org/10.1007/s00213-004-2032-2

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