Glucose intolerance with atypical antipsychotics.
BACKGROUND
Previous studies have suggested that the atypical antipsychotics clozapine and olanzapine may be associated with an increased risk of glucose intolerance and diabetes mellitus. Early studies have also suggested an association between use of conventional antipsychotics and the development of glucose intolerance.


OBJECTIVE
To examine quantitatively the association between glucose intolerance including diabetes mellitus and the use of the atypical antipsychotics clozapine, olanzapine or risperidone, and to identify possible risk factors for the development of glucose intolerance during treatment with these drugs.


METHODS
All reports suggestive of glucose intolerance for clozapine, olanzapine and risperidone were identified in the WHO database for adverse drug reactions. In the analyses of possible risk factors for glucose intolerance all other reports of adverse drug reactions for clozapine, olanzapine and risperidone were used as reference. Using the Bayesian Confidence Propagation Neural Network method, the strengths of the associations over time between glucose intolerance and the use of these drugs were analysed. For comparison, the strengths of the associations between glucose intolerance and the use of the conventional antipsychotics haloperidol and chlorpromazine were also analysed.


RESULTS
Clozapine, olanzapine and risperidone were significantly associated with glucose intolerance. In contrast, chlorpromazine and haloperidol were not associated with glucose intolerance. For clozapine, olanzapine and risperidone grouped together, the following potential risk factors for glucose intolerance were identified: an underlying diabetic condition (odds ratio [OR] 10.22, 95% CI 8.20-12.73), an increase in weight (OR 2.36, 95% CI 1.76-3.17), male gender (OR 1.27, 95% CI 1.11-1.47), and concomitant use of valproic acid (OR 1.97, 95% CI 1.61-2.40), selective serotonin reuptake inhibitors (OR 1.63, 95% CI 1.33-1.99) or buspirone (OR 2.24, 95% CI 1.33-3.77).


CONCLUSIONS
Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.
Hedenmalm
Karin
K
Drug Epidemiology Unit, Medical Products Agency, Uppsala, Sweden. karin.hedenmalm@mpa.se
Hägg
Staffan
S
Ståhl
Malin
M
Mortimer
Orjan
O
Spigset
Olav
O
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001499:Bayes Theorem; D001569:Benzodiazepines; D002746:Chlorpromazine / Q000009:adverse effects / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000139:chemically induced; D018149:Glucose Intolerance / Q000139:chemically induced*; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012307:Risk Factors; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D014944:World Health Organization
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine; D002746:Chlorpromazine