This study will determine the effectiveness of treatment with glycine or d-cycloserine in addition to a normal antipsychotic regimen in improving negative symptoms and cognitive impairments in patients with schizophrenia.

A double-blind, placebo controlled clinical trial to examine whether adjunctive treatment with glycine or d-cycloserine, compared to placebo, will improve negative symptoms and cognitive impairments in patients with schizophrenia who remain on their normal antipsychotic regimen.

Multicenter, randomized, double-blinded placebo controlled parallel-groups clinical trial designed to test the hypothesis that interventions (glycine or d-cycloserine) intended to increase glutamatergic activity by action at the NMDA receptor will reduce persistant negative symptoms and cognitive impairments of patients with schizophrenia or schizoaffective disorder. After an initial screening phase to establish clinical stability and eligibility, patients were assigned to one of three adjunctive treatments (placebo, d-cycloserine or glycine)for 16 weeks of double-blind treatment. Patients remained on a stable dose of antipsychotic therapy (other than clozapine) throughout the study.

Inclusion Criteria:

• diagnosis of schizophrenia or schizoaffective disorder
• stable, enduring negative symptoms above a certain level (SANS >19)
• clinically stable, with psychotic symptoms measured on BPRS below 19, anxiety/depression on BPRS below 15
• extrapyramidal symptoms measured on SAS below 9
• on stable antipsychotic regimen (not including clozapine)

Exclusion Criteria:

• alcohol or substance dependence within last six months
• alcohol or substance abuse within last month
• organic brain disorder
• medical condition whose pathology or treatment could alter the presentation or treatment of schizophrenia, including active tuberculosis or tuberculosis treatment, kidney stones, and uncontrolled diabetes mellitus
• Female participants could not be pregnant and were required to be using a documented method of contraception.