1. ¹Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
2. ²Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

Correspondence: Dr J Sacher, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Tel: +43 1 40400 3837; Fax: +43 1 40400 3825; E-mail: julia.sacher@univie.ac.at

Received 30 March 2007; Revised 25 June 2007; Accepted 23 July 2007; Published online 22 August 2007.

Abstract

Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n=14) or ziprasidone 80 mg/day (n=15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg (=mean, SM=0.4 ml/h/kg) at baseline to 4.7 ml/h/kg (=mean, SM=0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.20.3 ml/h/kg baseline vs 5.10.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.