Novel antipsychotics and new onset diabetes

• Published in: Biological psychiatry (1969) 1998-10, Vol.44 (8), p.778-783
• Main Authors: Wirshing, Donna A., Spellberg, Brad J., Erhart, Stephen M., Marder, Stephen R., Wirshing, William C.
• Format: Article
• Language: English
• Subjects: Adult; Antipsychotic Agents - adverse effects; atypical antipsychotic; Benzodiazepines; Biological and medical sciences; Clozapine; Clozapine - adverse effects; diabetes; Diabetes Mellitus, Type 2 - chemically induced; Drug toxicity and drugs side effects treatment; Humans; Male; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Olanzapine; Pharmacology. Drug treatments; Pirenzepine - adverse effects; Pirenzepine - analogs & derivatives; Psychotic Disorders - drug therapy; Risk Factors; Schizophrenia - drug therapy; serotonin; side effect
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(98)00100-0

Background: The new antipsychotics induce minimal extrapyramidal side effects, probably due to their relatively greater affinity for certain nondopaminergic receptors than their older, conventional counterparts; however, this polyreceptor affinity may be responsible for the development of other adverse effects. One serious adverse effect that may be linked to these effects is non–insulin-dependent diabetes mellitus. Methods: We summarize 6 new cases of clozapine- and olanzapine-associated diabetes that we have documented in our clinic. We compare our cases to previous reports and tabulate the pertinent similarities among cases. Results: Two of the cases were olanzapine-associated and 4 were clozapine-associated diabetes. Five of our 6 patients had risk factors for diabetes, as have 7 of the 9 previously reported in the literature. Four of our 6 patients, and 2 of the 4 prior cases in which such data were reported, experienced substantial weight gain after starting their antipsychotics. Conclusions: Novel antipsychotics should be administered with great care to patients with risk factors for diabetes. Although the precise mechanism of the novel antipsychotic-associated diabetes is unclear, we hypothesize that histaminic and possibly serotonergic antagonism induces weight gain, which in turn leads to changes in glucose homeostasis. Additionally, serotonin 1A antagonism might decrease pancreatic β-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia.