NOVEL ANTIPSYCHOTICS AND NEW-ONSET DIABETES

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 devel opment of other adverse effects. One serious adverse effect that may b e linked to these effects is non-insulin-dependent diabetes mellitus. Methods: We summarize 6 new cases of clozapine- and olanzapine-associa ted diabetes that we have documented in our clinic. We compare our cas es to previous reports and tabulate the pertinent similarities among c ases. 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 literatur e. Four of our 6 patients, and 2 of the 4 prior cases in which such da ta were reported, experienced substantial weight gain after starting t heir antipsychotics. Conclusions: Novel antipsychotics should be admin istered with great care to patients with risk factors for diabetes. Al though the precise mechanism of the novel antipsychotic-associated dia betes is unclear, we hypothesize that histaminic and possibly serotone rgic antagonisin induces weight gain, which in turn leads to changes i n glucose homeostasis. Additionally, serotonin,, antagonism might decr ease pancreatic beta-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia. Biol Psychiatry 1998;44: 778-783 (C) 1 998 Society of Biological Psychiatry.