Risperidone-associated diabetes mellitus: a pharmacovigilance study

Pharmacotherapy. 2003 Jun;23(6):735-44. doi: 10.1592/phco.23.6.735.32178.


Study objective: To explore the clinical characteristics of hyperglycemia in patients treated with risperidone.

Design: Pharmacovigilance survey of spontaneously reported adverse events in risperidone-treated patients, with reports of haloperidol-associated hyperglycemia used as a control.

Setting: Government-affiliated drug evaluation center.

Intervention: The Food and Drug Administration MedWatch surveillance program was queried (risperidone, 1993-February 2002; haloperidol, late 1970s-February 2002) and results pooled with published cases.

Measurements and main results: We identified 131 reports of risperidone-associated hyperglycemia in addition to seven reports of patients with hyperglycemia who received combined risperidone-haloperidol therapy and six reports of acidosis that occurred in the absence of hyperglycemia. We found 13 reports of haloperidol-associated hyperglycemia and 11 reports of acidosis without hyperglycemia. Of the reports of risperidone-associated hyperglycemia (monotherapy), 78 patients had newly diagnosed hyperglycemia, 46 had exacerbated preexisting diabetes, and 7 could not be classified. Mean +/- SD age was 39.8 +/- 17.4 years (range 8-96 yrs). Patients with new-onset diabetes (mean +/- SD age 34.8 +/- 15.7 yrs) were younger than those with preexisting diabetes (mean +/- SD age 48.8 +/- 17.5 yrs). The overall male:female ratio was 1.5. In most patients, hyperglycemia appeared within 3 months of the start of risperidone therapy. Severity of disease ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. Twenty-six patients with acidosis or ketosis were reported. Four patients died.

Conclusion: Atypical antipsychotic treatment may unmask or precipitate hyperglycemia. Although such cases attributed to clozapine or olanzapine are more numerous than those associated with risperidone, the number for risperidone-associated hyperglycemia is relatively higher than that observed with the conventional neuroleptic haloperidol.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / adverse effects*
  • Child
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / etiology*
  • Drug Therapy, Combination
  • Drug Utilization Review*
  • Female
  • Haloperidol / adverse effects*
  • Humans
  • Hyperglycemia / epidemiology
  • Hyperglycemia / etiology
  • Male
  • Middle Aged
  • Product Surveillance, Postmarketing
  • Risk Factors
  • Risperidone / adverse effects*
  • United States / epidemiology


  • Antipsychotic Agents
  • Haloperidol
  • Risperidone