A placebo-controlled crossover trial of -cycloserine added to clozapine in patients with schizophrenia

Background: -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, in one preliminary dose-finding study, worsened negative symptoms when added to clozapine. Methods: Seventeen schizophrenia outpatients treated with clozapine were assigned in random order to 6-week trials of -cycloserine 50 mg/day and placebo in a crossover design separated by a 1 week placebo washout. Results: Eleven patients competed the 13-week study. -Cycloserine significantly worsened ratings of negative symptoms compared to placebo but did not significantly affect ratings of psychotic symptoms. Conclusions: The differing effects of -cycloserine on negative symptoms when added to clozapine compared to conventional antipsychotics suggests that activation of the glycine recognition site may play a role in clozapine’s efficacy for negative symptoms.