Original Research Article Indian Journal of Neurosciences, July-September,2016;2(3):64-68 64 A 6 week prospective randomized comparative study of metabolic adverse effects of Risperidone and Iloperidone in patients with schizophrenia Anil Kumar Mysore Nagaraj 1* , Priya Janardhan 2 , Basavanna PL 3 , Rajendra Rajagopal 4 1 Assistant Professor, 2 Post Graduate Student, 3 Professor, 4 Associate Professor, Dept. of 1,4 Psychiatry, 2,3 Pharmacology, Mysore Medical College & Research Institute, Mysore, Karnataka *Corresponding Author: E-mail: nagarajakm24@gmail.com Abstract Introduction: The antipsychotics Risperidone and Iloperidone are the two different benzisoxazole derivatives that are structurally different and metabolized differently. Risperidone has moderate effects on metabolic parameters. Iloperidone is comparable to placebo in this regard according to western literature. We wish to study this on Indian population. Methods: it is a prospective randomized study having three visits, on day 1, 21 and 42. Forty patients with schizophrenia, 20 each on Risperidone and Iloperidone were compared for weight, BMI, FBS, PPBS and fasting lipid profile using repeated measures ANOVA and t test. Results: Ten percent of subjects on Risperidone and 15% on Iloperidone had significant weight gain. The mean weight gain was 2.5 kg and 2.75 kg with Risperidone and Iloperidone respectively. Both weight and BMI were comparable. Within the group, Risperidone caused significant rise in lipids; where as Iloperidone caused significant increase in both lipids and sugar. Across the groups there was no significant difference. Conclusions: The study reveals that Iloperidone is associated with weight gain, change in BMI as well as alteration in blood sugar and lipids that is comparable with Risperidone, even at a lower chlorpromazine equivalent dose, in contrast to the western literature where, its impact on metabolic parameters are said to be at placebo level. Keywords: BMI, Cholesterol, FBS, Ilopridone, PPBS, Risperidone, Triglycerides, Weight gain. Introduction Risperidone and Iloperidone are the second generation antipsychotics (SGA). Risperidone is a benzisoxazole derivative and an approved antipsychotic agent for the treatment of schizophrenia and the acute manic phase of bipolar disorder. It has a strong binding affinity for serotonin (5-HT2A and 5-HT7) and dopamine D2 receptors. It has a lower acute incidence of overall adverse effects than Haloperidol at therapeutic dosages of 4-6 mg/day (1,2) . Extrapyramidal syndromes and sequelae of prolactin elevation have been the common and consistent adverse effects of Risperidone. Though there is an active weight gain, it tends to plateau within a few months (3,4) . The CATIE trial reported an average weight gain of 0.8 lb with Risperidone. About 14% subjects gained more than 7% of their body weight (5) . The risk of developing type 2 DM with risperidone comes after that of clozapine and olanzapine (6) . Studies have consistently found that Risperidone causes hyperlipidemia less frequently than clozapine and olanzapine. Possible underlying causes of lipid dysregulation include weight gain, dietary changes, and glucose intolerance (7,8) . Iloperidone was approved in 2009 by the US Food and Drug Administration for the acute treatment of schizophrenia (9) . It belongs to the class of piperidinyl- benzisoxazole derivatives. Though structurally similar to Risperidone, it does not have a tricyclic structure like other SGAs. Further, it is metabolized differently because it lacks the piperidinyl ring found in Risperidone. Thus it is neither a metabolite of Risperidone nor does its metabolites produce any metabolites in common with other agents. It shows high affinity for dopamine D3 receptors, 5HT2A receptors, norepinephrine α1/α2c receptors apart from D2. Low affinity to histamine H1 receptors would theoretically predict a low propensity for causing sedation or weight gain (10) . Twelve percent of patients experienced clinically significant weight gain, largely during initiation phase of treatment (11) . Another study revealed that Iloperidone, Paliperidone, Quetiapine, and Risperidone have a medium risk of glucose dysregulation and weight gain, as compared to Olanzapine and Clozapine which have highest risk (12) . In the long term studies of Iloperidone and Haloperidol, increase in the levels of total cholesterol and triglycerides were numerically larger in patients receiving haloperidol (13) . Thus studies have shown that both Risperidone and Iloperidone have some metabolic adversities, though not as severe as Olanzapine. Iloperidone being a newer second generation antipsychotic drug, has been shown to have a safe metabolic profile. Our objective is to test this and compare the two drugs on Indian population. Methods The study was approved by the institutional ethics committee. This is a prospective randomized comparative study wherein we assessed the metabolic parameters of patients with schizophrenia, who were administered a monotherapy with Risperidone or Iloperidone. The study was conducted in the department