Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: A double-blind, placebo-controlled trial

Abstract 

Background

Olanzapine associated weight gain (WG) is a major concern in patients with schizophrenia. The purpose of this study was to assess the efficacy of topiramate to prevent olanzapine induced WG in these cases. We also studied various metabolic parameters.

Methods

In this 12-week, double-blind, parallel group study, seventy-two drug-naïve, first-episode schizophrenia patients were randomized to receive olanzapine+placebo (olanzapine group) or olanzapine+topiramate (100mg/day) (topiramate group). Weight, body mass index, fasting glucose, insulin, insulin resistance (IR), leptin, lipids and blood pressure were assessed at baseline and at 12weeks. The patients were clinically evaluated using Positive and Negative Syndrome Scale (PANSS) and were monitored for adverse effects.

Results

Topiramate resulted in a weight loss of 1.27±2.28kg (p<0.01), decrease in leptin (p<0.001), glucose, cholesterol, triglyceride levels and systolic and diastolic blood pressure. In the olanzapine group, there was a significant WG, hyperglycemia, hyperinsulinemia, increased IR, hyperleptinemia, hypercholesterolemia and hypertriglyceridemia (p<0.001).There was a greater clinical improvement (PANSS scores) (p<0.001) in the topiramate group. The adverse effects were well tolerated.

Conclusions

Topiramate could prevent olanzapine induced weight gain and adverse metabolic effects. It also results in a greater clinical improvement when used with olanzapine in schizophrenia.

Abbreviations: WG, Weight gain, BMI, Body mass index, FBG, Fasting blood glucose, TC, Total cholesterol, IR, Insulin resistance

Keywords: Schizophrenia, Olanzapine, Topiramate, Weight, Metabolic syndrome, Leptin