Severe weight gain induced by combination treatment with risperidone and paroxetine

Successful combination therapy with atypical antipsychotics and selective serotonin reuptake inhibitors has been reported for several psychiatric conditions. However, great attention should be paid to the possible adverse effects. In this retrospective chart review, we focused on the drug-drug interaction of paroxetine and risperidone. Retrospectively, we identified two patients treated with a combination of risperidone and paroxetine therapy, and analyzed their medical records. During a 3-month period of monotherapy with risperidone, the changes in body weight were +/- 0.0 kg in Patient 1 and -2.0 kg in Patient 2. In contrast, during combination therapy with paroxetine and risperidone, the body-weight changes were +14.0 kg in Patient 1 (after 4 months) and +13.5 kg in Patient 2 (after 5 months). In addition, diabetes mellitus was observed in Patient 2. Regarding the mechanism of severe weight gain in these two patients, we speculate a drug-drug interaction involving inhibition of the cytochrome P450 enzyme 2D6 (CYP4502D6) by paroxetine.