A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia

Background: In a preliminary dose-finding study, D-cycloserine, a partial a gonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspar tate (NMDA) receptor, improved negative symptoms and cognitive function whe n added to conventional neuroleptics at a dose of 50 mg/d. Methods: Forty-seven patients with schizophrenia meeting criteria for defic it syndrome were randomized to D-cycloserine, 50 mg/d (n = 23) or placebo ( n = 24) added to their conventional neuroleptic for an 8-week, double-blind trial. Clinical assessments were performed at baseline and at weeks 1, 2, 4, 6, and 8. Serum concentrations of D-cycloserine. relevant amino acids, a nd homovanillic acid were assayed at baseline and at weeks 4 and 8. A cogni tive battery was performed at baseline and at week 8. Results: Thirty-nine patients completed the 8-week trial. Seven dropouts oc curred in the D-cycloserine group and 1 in the placebo group. The mean redu ction in negative symptoms with D-cycloserine (23%) was significantly great er than with placebo (7%) as calculated by slopes representing Scale for th e Assessment of Negative Symptoms (SANS) total scores. Improvement of negat ive symptoms was predicted by low neuroleptic dose and low baseline SANS to tal score. No differences were found in performance on any cognitive test b etween groups or in changes in any other clinical measure. Clinical respons e did not correlate significantly with serum amino acid concentrations at b aseline or with concentrations of D-cycloserine at weeks 4 and 8. Conclusion: These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative sympt oms.