N-methyl-D-aspartate receptor (NMDAR) agonist, added to classical or atypical antipsychotic
medication, has reduced negative, depressive, and cognitive symptomatology. We will be
investigating the effect of D-serine, (DSR), a selective and potent NMDAR agonist, as
monotherapy for treatment resistant schizophrenics.
40 subjects on stable doses of risperidone will be randomized under double-blind conditions
into a treatment group, which will receive D-serine 2100 mg, or a control group, which will
continue to receive risperidone. Treatment will continue for 14 weeks.
Symptoms and side effects will be rated biweekly with the CGI, PANSS, BPRS, SAS, AIMS, and
UKU. Before and after the trial subjects will undergo neuropsychological assessments.
Baseline and post-trial levels of amino acids relevant to glutamatergic neurotransmission
(glutamate, glutamine, aspartate, glycine, serine, alanine) will be assessed.
The primary outcome measures of the study will be the PANSS total scores and the positive and
negative symptom cluster scores.