There is extensive evidence that clozapine and olanzapine produce the largest increase in weight or BMI among the atypical antipsychotic drugs. There is also considerable, if controversial evidence, that clozapine-induced weight gain is predictive of clinical response in patients with schizophrenia.

The aim of this study was to determine if weight gain and changes in metabolic measures with olanzapine and risperidone also predict clinical response in patients with schizophrenia, schizoaffective disorder, or bipolar disorder.

Data from a 12 month, randomized, prospective study of the effects of olanzapine and risperidone in 160 patients with schizophrenia (SCH) and schizoaffective disorder (SAD), and bipolar disorder (BPD) on weight gain, BMI increase and metabolic measures including fasting blood glucose, hemoglobin A1c, total cholesterol, triglycerides, HDL, triglycerides/HDL ratio, log triglycerides, LDL to predict improvement in PANSS total scores.

Weight gain and increase in BMI predicted the clinical response to olanzapine, but not risperidone, in patients with SCH or SAD, but not BPD, at 1, 3 and 6 months, when used in combination with other psychotropic medications or no concomitant mood stabilizers. Changes in lipid and glucose measures did not predict response to either drug.

Olanzapine-induced weight and BMI increase predicted decrease in PANSS total score at 1, 3, 6 months. No such relationship was found for risperidone- treated patients in either diagnostic group. These results suggest weight gain and clinical response to olanzapine and clozapine may be based on similar mechanism which differentiates them from risperidone.