Association of weight gain and metabolic syndrome in patients taking clozapine: an 8-year cohort study

J Clin Psychiatry. 2011 Jun;72(6):751-6. doi: 10.4088/JCP.09m05402yel. Epub 2010 Nov 30.


Introduction: Metabolic syndrome is an important side effect associated with clozapine. It has been hypothesized that weight gain contributes to the development of metabolic syndrome, but a direct diabetogenic effect has also been suggested. We conducted an 8-year cohort study to determine the association between weight gain and metabolic parameters among schizophrenic patients taking clozapine.

Method: This study is a retrospective cohort study combining a cross-sectional survey of metabolic syndrome and retrospective chart review. The subjects were hospitalized schizophrenic patients (DSM-IV) who began to receive clozapine at least 3 months before the survey (March to September 2005) and subsequently had monthly body weight monitoring. Anthropometric and biochemical measurements were performed to determine the presence of metabolic syndrome. The chart reviews were conducted to obtain gender, age at initiation of clozapine treatment, baseline body mass index (BMI), BMI changes after the initiation of clozapine treatment, treatment duration with clozapine, and concomitant psychotropic medications.

Results: One hundred eighty-nine patients were maintained on clozapine for a mean ± SD treatment duration of 57.6 ± 27.3 months (range, 5-96). The prevalence of metabolic syndrome was 28.4%. The cohort regression models showed that baseline BMI (P < .01) and BMI change after clozapine treatment (P < .01) were significant factors for metabolic syndrome and 4 metabolic parameters except hyperglycemia, which was related to treatment duration (P < .05).

Conclusions: For patients treated with clozapine, metabolic syndrome and most metabolic parameters were related to weight gain; however, glucose dysregulation was associated with treatment duration independent of weight gain. The results confirm that monitoring body weight is important, but periodic monitoring of blood sugar may also be required for clozapine patients who do not have significant weight gain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Body Mass Index
  • Clozapine / adverse effects*
  • Clozapine / therapeutic use
  • Cross-Sectional Studies
  • Female
  • Humans
  • Logistic Models
  • Male
  • Metabolic Syndrome / chemically induced*
  • Regression Analysis
  • Retrospective Studies
  • Schizophrenia / drug therapy
  • Sex Factors
  • Weight Gain / drug effects*


  • Antipsychotic Agents
  • Clozapine