28. Metabolic Adverse Effects Associated with Antipsychotic Medications

  1. Daniel R. Weinberger MD4 and
  2. Paul J. Harrison MA, BM, BCh, DM(Oxon), FRCPsych5
  1. John W. Newcomer MD1,2 and
  2. Stefan Leucht MD3

Published Online: 8 MAR 2011

DOI: 10.1002/9781444327298.ch28

Schizophrenia, Third Edition

Schizophrenia, Third Edition

How to Cite

Newcomer, J. W. and Leucht, S. (2010) Metabolic Adverse Effects Associated with Antipsychotic Medications, in Schizophrenia, Third Edition (eds D. R. Weinberger and P. J. Harrison), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444327298.ch28

Editor Information

  1. 4

    Genes, Cognition and Psychosis Program, Clinical Studies Section, Clinical Brain Disorders Branch, National Institute of Health, Bethesda, MD, USA

  2. 5

    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK

Author Information

  1. 1

    Gregory B. Couch Professor of Psychiatry, Psychology and Medicine, USA

  2. 2

    Washington University School of Medicine, St. Louis, MO, USA

  3. 3

    Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Munich, Germany

Publication History

  1. Published Online: 8 MAR 2011
  2. Published Print: 10 DEC 2010

ISBN Information

Print ISBN: 9781405176972

Online ISBN: 9781444327298



  • antipsychotic;
  • metabolic;
  • diabetes;
  • weight;
  • adiposity;
  • lipids;
  • glucose;
  • cardiovascular disease


Compared with the general population, individuals with schizophrenia are at increased risk for premature mortality related primarily to coronary heart disease, with additional contributions to overall excess mortality from conditions like suicide, chronic respiratory disease, diabetes, and cerebrovascular disease. Major modifiable risk factors for cardiovascular disease include obesity, dyslipidemia, hyperglycemia, hypertension, and smoking. These risk factors are all more prevalent in subjects with schizophrenia compared to the general population, with increased adiposity a commonly occurring key factor underlying the development of additional risks. Individuals with schizophrenia have increases in adiposity for a variety of reasons, including poor diet and reduced activity related to hospitalizations, poverty, and illness-related behaviors, as well as medication effects such as sedation and increased food intake. This chapter provides an overview of evidence that antipsychotic medication treatment can increase body weight and adiposity, decrease insulin sensitivity, and induce adverse changes in plasma lipids and glucose homeostasis, with the magnitude of effects varying across individual medications. Observed treatment effects on body weight, adiposity, and specific metabolic risk factors are highly variable overall, dependent on individual medication effects, individual patient characteristics, duration of treatment, concomitant medications and prior treatment conditions. For antipsychotics, the magnitude of body weight change during treatment can be largely explained by the H1 receptor affinity of the individual medication, where H1 antagonist activity can reduce caloric expenditure via sedation and increase caloric intake via the attenuation of satiety. Other medications commonly used in the treatment of schizophrenia, including antidepressants and putative mood stabilizers, can also contribute to weight gain and metabolic risk, although characterization of the magnitude and mechanisms underlying these effects remains more limited than that for antipsychotic medications. Appropriate screening, monitoring, and targeted interventions are required to manage potential metabolic adverse events occurring during antipsychotic treatment. While a number of promising programs have been initiated, reports to date suggest limited success in increasing needed clinical vigilance in this area.