D-cycloserine increases positive symptoms in chronic schizophrenic patients when administered in addition to antipsychotics: A double-blind, parallel, placebo-controlled study

A hypofunction of the glutamatergic system and NMDA receptors in schizophre nia has been hypothesized. Therefore, stimulation of these receptors could be of benefit to patients with schizophrenia. D-cycloserine has been used f or this purpose. This study reports the effects of 100 mg D-cycloserine, wh en added to typical antipsychotics in chronic schizophrenic patients exhibi ting prominent negative symptoms, using a placebo-controlled, double-blind, parallel, design. D-cycloserine slightly worsened psychotic symptoms and g eneral psychopathology as compared to placebo. D-cycloserine failed to chan ge negative symptoms and had no effect on extrapyramidal symptoms. The exac erbation of schizophrenic symptoms may be explained by the antagonistic eff ects of this dose of D-cycloserine at the glycine recognition site of the N MDA receptor due to competition with the endogenous agonist glycine. Anothe r explanation for the increase in psychopathology may be an interaction wit h the effects of antipsychotics on NMDA mediated neurotransmission. Thus, D -cycloserine in this study did not ameliorate schizophrenic symptoms. Howev er, the fact that they actually worsened suggests that NMDA systems may be involved in the pathogenesis of schizophrenia. Further placebo-controlled s tudies with lower dosages of D-cycloserine, preferably in drug-free patient s,are necessary to evaluate if D-cycloserine is of use for the treatment of patients with schizophrenia. (C) 1999 American College of Neuropsychopharm acology. Published by Elsevier Science Inc.