Schizophrenia Research
Volume 56, Issue 1 , Pages 19-23, 1 July 2002

d-Cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia

  • A.Eden Evins

      Affiliations

    • Harvard Medical School and the Schizophrenia Research Program of the Massachusetts General Hospital, Freedom Trail Clinic, 25 Staniford Street, Boston, MA 02114, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-617-912-7832; fax: +1-617-723-3919
    • ,
  • Ed Amico

      Affiliations

    • Harvard Medical School and the Schizophrenia Research Program of the Massachusetts General Hospital, Freedom Trail Clinic, 25 Staniford Street, Boston, MA 02114, USA
    • ,
  • Thomas A. Posever

      Affiliations

    • Tufts University School of Medicine and the Bay Cove Mental Health Center, Lemuel Shattuck Hospital, Morton Street, Jamaica Plain, MA 02130, USA
    • ,
  • Rob Toker

      Affiliations

    • Tufts University School of Medicine and the Bay Cove Mental Health Center, Lemuel Shattuck Hospital, Morton Street, Jamaica Plain, MA 02130, USA
    • ,
  • Donald C. Goff

      Affiliations

    • Harvard Medical School and the Schizophrenia Research Program of the Massachusetts General Hospital, Freedom Trail Clinic, 25 Staniford Street, Boston, MA 02114, USA

Received 28 November 2000; received in revised form 15 March 2001; accepted 19 March 2001.

Abstract 

Background. d-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor has previously been shown to improve negative symptoms when added to conventional antipsychotics and to worsen negative symptoms when added to clozapine. The purpose of this study was to examine the effects of d-cycloserine when added to risperidone on negative symptoms of schizophrenia.

Method. Ten patients with schizophrenia who were treated with risperidone completed consecutive two week trials of placebo and four doses of d-cycloserine. Clinical assessments were videotaped and were scored by a rater who was blind to temporal sequence.

Results. d-Cycloserine at a dose of 50mg/day was associated with significant reduction in negative symptoms (mean=10%). Ratings of depression, extrapyramidal side effects, and cognitive function were unchanged. Serum concentrations of glutamate and serine increased significantly on this dose of d-cycloserine.

Conclusions. This preliminary study suggests that combination of d-cycloserine, 50mg/day, with risperidone may improve negative symptoms of schizophrenia over a narrow dose range. The degree of improvement appears to be intermediate between improvement of negative symptoms observed with combination of d-cycloserine with conventional antipsychotics and worsening of negative symptoms observed with combination of d-cycloserine with clozapine in previous trials of identical design.

Keywords: d-Cycloserine, Glutamate, Glycine, Negative symptoms, NMDA, Schizophrenia

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PII: S0920-9964(01)00220-1

doi:10.1016/S0920-9964(01)00220-1

Schizophrenia Research
Volume 56, Issue 1 , Pages 19-23, 1 July 2002

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