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Glucose intolerance with atypical antipsychotics
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Norrland University Hopital, Umeå.
WHO Uppsala Monitoring Centre, Uppsala.
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2002 (English)In: Drug Safety, ISSN 0114-5916, Vol. 25, no 15, 1107-1116 p.Article in journal (Refereed) Published
Abstract [en]

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). CONCLUSION: Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.

Place, publisher, year, edition, pages
2002. Vol. 25, no 15, 1107-1116 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-93243PubMedID: 12452735OAI: oai:DiVA.org:uu-93243DiVA: diva2:166668
Available from: 2005-06-02 Created: 2005-06-02 Last updated: 2010-03-04Bibliographically approved
In thesis
1. Hazards of Drug Therapy: On the Management of Adverse Drug Reactions: From Signal Detection and Evaluation to Risk Minimization
Open this publication in new window or tab >>Hazards of Drug Therapy: On the Management of Adverse Drug Reactions: From Signal Detection and Evaluation to Risk Minimization
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) have been developed as a result of the thalidomide disaster, whereby thousands of children world-wide were born with birth defects. The Swedish Adverse Drug Reactions Advisory Committee was established in 1965. Since 1975, reporting has been compulsory for all suspected serious or new ADRs. International collaboration started in 1968 with countries contributing their ADR reports to an international database set up by the World Health Organization.

ADRs represent the negative side of the benefit-to-risk balance that in theory needs to be counteracted by perceived or established positive drug effects. All drugs are subject to preclinical and clinical testing prior to marketing authorization. However, these studies are insufficient to detect rare ADRs, ADRs that occur after long-term administration or with latency, ADRs that occur in special patient groups such as children, the elderly, patients with renal or hepatic insufficiency or patients on concomitant drug treatment, and ADRs that represent a modest increase in the risk of diseases (including mortality) that are prevalent in the study population. Postmarketing surveillance of drugs is therefore essential, and regulatory action may be needed on the basis of new ADR information.

SRSs are important sources of ADR information as exemplified here by the evaluation of peripheral sensory disturbances with fluoroquinolones, hyponatremia with antidepressants, blood dyscrasias with dipyrone, glucose intolerance with atypical antipsychotics, pulmonary embolism with combined oral contraceptives and extrapyramidal symptoms with selective serotonin reuptake inhibitors. SRSs can be used to study clinical manifestations of ADRs (that can give insights into potential ADR mechanisms), risk factors for the ADR or for specific outcomes of the ADR, and ADR reporting incidences when combined with sales data. Signals from SRSs may need to be studied further e.g., by use of large-scale epidemiologic studies based on record linkage between drug prescription databases and health databases. Owing to the rapid availability of information, however, SRSs are likely to remain of major importance for the post-marketing surveillance of drugs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 86 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 54
Pharmacology, adverse drug reactions, spontaneous reporting systems, drug regulation, pharmacovigilance, incidence, Farmakologi
National Category
Pharmacology and Toxicology
urn:nbn:se:uu:diva-5866 (URN)91-554-6291-X (ISBN)
Public defence
2005-09-16, Enghoffsalen, Ingång 50, Akademiska sjukhuset, Uppsala, 09:15
Available from: 2005-06-02 Created: 2005-06-02Bibliographically approved

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