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 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, serotonin1A antagonism might decrease pancreatic beta-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia.
Wirshing
D A
DA
Department of Psychiatry, West Los Angeles Veterans Affairs Medical Center, CA 90073, USA.
Spellberg
B J
BJ
Erhart
S M
SM
Marder
S R
SR
Wirshing
W C
WC
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines; D003024:Clozapine / Q000009:adverse effects*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives*; D011618:Psychotic Disorders / Q000188:drug therapy; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D000077152:Olanzapine