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Double-blind, placebo-controlled, crossover trial of d-cycloserine adjuvant therapy for treatment-resistant schizophrenia

Uriel Heresco-Levy, Daniel C. Javitt, Marina Ermilov, Gail Silipo, Jonathan Shimoni
DOI: http://dx.doi.org/10.1017/S1461145798001242 131-135 First published online: 1 December 1998


Dysfunction of N-methyl-d-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission may be relevant to the pathogenesis of negative symptoms in schizophrenia. The tuberculostatic compound d-cycloserine (DCS) acts as a partial agonist at the strychnine-insensitive glycine regulatory site on the NMDA receptor complex. Dose-finding trials suggest that DCS doses of 50–100 mg/d may be beneficial in the treatment of negative symptoms in schizophrenia. Nine treatment-resistant chronic schizophrenic patients participated in a double-blind, placebo-controlled, adjuvant treatment trial with 50 mg/d DCS. Between treatment-groups differences in symptom changes were not significant. However, a significant (p < 0.05) reduction in negative symptoms was registered during treatment with DCS but not placebo. Greater reductions were registered in patients with lower baseline serum glycine levels (p < 0.008). No side effects were registered. These preliminary findings indicate a potential role of DCS in the treatment of negative symptoms in schizophrenia. However, the degree of symptom reduction may be modest, at least among treatment-resistant inpatients.

Key words
  • Schizophrenia
  • negative symptoms
  • N-methyl-d-aspartate receptor
  • d-cycloserine