Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (−141 C Ins/Del) and 5HTR2C (−759 C>T) Genetic Polymorphisms in Patients with Schizophrenia

Objective: To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 − 141 C Ins/ Del/rs1799732) and serotonin receptor (5HTR2C −759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia. Materials and Methods: The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4–8 mg/day)‑based therapy for a minimum of 4 weeks. Genotyping was carried by real‑time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively. Results: Risperidone‑induced extrapyramidal symptoms(EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone‑induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 −141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29–84.89, P = 0.004). No such association was observed with 5HTR2C (−759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms. Conclusion: Hyperprolactinemia, weight gain, and EPSs(>36.7%) were common adverse effects of risperidone. DRD2 – 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone.