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Hyperglycemia Associated With the Use of Atypical Antipsychotics

Jean-Pierre Lindenmayer, MD; Ann-Marie Nathan, MA; and Robert C. Smith, MD, PhD

Published: January 9, 2001

Article Abstract

The available literature suggests that patients with schizophrenia are at risk for diabetes mellitusand taking antipsychotic medication further increases the chance of developing non-insulin-dependenthyperglycemia. Case reports, chart reviews, and some results from clinical drug trials implicate a relationshipbetween glucose levels and treatment with clozapine or olanzapine in patients with schizophrenia,although a few cases of hyperglycemia have also been reported in patients taking risperidoneand quetiapine. These studies indicate that hyperglycemia is not dose dependent, is reversible on cessationof treatment with clozapine or olanzapine, and reappears on reintroduction of these therapies. Thepostulated underlying mechanisms involved in this process in patients with schizophrenia include (1) adecreased sensitivity to insulin that is independent of atypical medication, (2) an increased insulin resistancerelated to atypical medications, (3) the effects of atypical medications on serotonin receptors,and (4) overuse of insulin due to weight gain. These mechanisms are discussed in detail, and recommendationsfor the administration of atypical antipsychotics are offered. Overweight, ethnicity, familyor personal history of diabetes mellitus or hypertension, and weight gain during the course of treatmenthave all been identified as risk factors in the development of hyperglycemia in patients with schizophrenia.However, it is difficult to statistically assess the true incidence of diabetes within each type ofantipsychotic medication group with the exclusive dependence on available case studies and withoutproper epidemiologic research.

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