Weight Gain and Changes in Metabolic Variables following Olanzapine Treatment in Schizophrenia and Bipolar Disorder Leslie Citrome, 1 Richard I.G. Holt, 2 Daniel J. Walker 3 and Vicki Poole Hoffmann 3 1 Department of Psychiatry, New York University School of Medicine, New York, USA 2 Developmental Origins of Health and Disease Division, School of Medicine, University of Southampton, Southampton, UK 3 Eli Lilly and Company, Indianapolis, Indiana, USA Contents Abstract ................................................................................. 455 1. Introduction .......................................................................... 456 2. Literature Search Methodology .......................................................... 457 3. Changes in Weight with Olanzapine ...................................................... 457 3.1 Patients at Higher Risk of Weight Gain ................................................ 466 3.2 Predictability of Weight Gain ........................................................ 467 4. Changes in Metabolic Variables with Olanzapine .......................................... 468 4.1 Diabetes Mellitus .................................................................. 468 4.1.1 Prevalence ................................................................. 468 4.1.2 Underlying Mechanisms ....................................................... 468 4.1.3 Antipsychotics and Diabetes .................................................. 470 4.2 Changes in Lipid Variables .......................................................... 472 5. Cardiovascular Mortality in Patients taking Antipsychotics ................................... 474 6. Prevention and Management Strategies .................................................. 475 7. Conclusions ........................................................................... 476 Abstract Antipsychotic therapy forms the cornerstone of treatment for people with severe mental illness. Second-generation (atypical) antipsychotics are asso- ciated with a significantly lower incidence of extrapyramidal symptoms than the typical, first-generation agents; however, changes in metabolic variables – including impaired glucose metabolism, diabetes mellitus, weight gain and dyslipidaemia – have been reported during treatment with second-generation antipsychotics. Understanding any potential link between antipsychotic treatment and the incidence of these events is complicated by the increasing prevalence of obesity and diabetes occurring in the general population and the increased risk of diabetes and changes in metabolic variables in people with schizophrenia. While relative risk estimates are inconsistent, the asso- ciation between atypical antipsychotics and increases in glucose level appears to fall on a continuum, with olanzapine appearing to have a greater asso- ciation than some other atypical antipsychotics. The PubMed database was REVIEW ARTICLE Clin Drug Investig 2011; 31 (7): 455-482 1173-2563/11/0007-0455/$49.95/0 ª 2011 Adis Data Information BV. All rights reserved.