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

Background: D-Cycloserine, a partial agonist at the glycine recognition sir e of the NMDA receptor; has previously been shown to improve negative sympt oms when added to conventional antipsychotics and in one preliminary dose-f inding study, worsened negative symptoms when added to clozapine. Methods: Seventeen schizophrenia outpatients treated with clozapine were as signed in random order to 6-week trials of D-cycloserine 50 mg/day and plac ebo in a crossover des;gn separated by a I week placebo washout. Results: Eleven patients competed the 13-week study. D-Cycloserine signific antly worsened ratings of negative symptoms compared to placebo but did not significantly affect ratings of psychotic symptoms. Conclusions: The differing effects of D-cycloserine on negative symptoms wh en added to clozapine compared to conventional antipsychotics suggests that activation of the glycine recognition sire may play a role in clozapine's efficacy for negative symptoms. (C) 1999 Society of Biological Psychiatry.