Atypical Antipsychotics and Glucose Homeostasis
J Clin Psychiatry 2005;66(2):504-514
© Copyright 2016 Physicians Postgraduate Press, Inc.
Purchase This PDF for $40.00
If you are not a paid subscriber, you may purchase the PDF.
(You'll need the free Adobe Acrobat Reader.)
Receive immediate full-text access to JCP. You can subscribe to JCP online-only ($86) or print + online ($156 individual).
With your subscription, receive a free PDF collection of the NCDEU Festschrift articles. Hurry! This offer ends December 31, 2011.
If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
Click here to login.
Did you forget your password?
Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send email
Objectives: Persistent reports have linked
atypical antipsychotics with diabetes, yet causative mechanisms
responsible for this linkage are unclear. Goals of this review
are to outline the pathogenesis of nonimmune diabetes and to
survey the available literature related to why antipsychotics may
lead to this disease.
Data Sources: We accessed the literature
regarding atypical antipsychotics and glucose homeostasis using
PubMed. The search included English-language publications from
1990 through October 2004. Keywords used included atypical
antipsychotics plus one of the following: glucose, insulin, glucose tolerance, obesity, or diabetes. In
addition, we culled information from published abstracts from
several national and international scientific meetings for the
years 2001 through 2004, including the American Diabetes
Association, the International Congress on Schizophrenia
Research, and the American College of Neuropsychopharmacology.
The latter search was necessary because of the paucity of
well-controlled prospective studies.
Study Selection: We examined publications with
significant new data or publications that contributed to the
overall comprehension of the impact of atypical antipsychotics on
glucose metabolism. We favored original peer-reviewed articles
and were less likely to cite single case studies and/or anecdotal
information. Approximately 75% of the fewer than 150 identified
articles were examined and included in this review.
Data Extraction: Validity of data was evaluated
using the existence of peer-review status as well as our own
experience with methodology described in the specific articles.
Data Synthesis: The metabolic profile caused by
atypical antipsychotic treatment resembles type 2 diabetes. These
agents cause weight gain in treated subjects and may induce
obesity in both visceral and subcutaneous depots, as occurs in
diabetes. Insulin resistance, usually associated with obesity,
occurs to varying degrees with different antipsychotics, although
more comparative studies with direct assessment of resistance are
needed. A major problem in assessing drug effects is that
psychiatric disease itself can cause many of the manifestations
leading to diabetes, including weight gain and sedentary
lifestyle. While studies in healthy subjects are limited and
inconclusive, studies in animal models are more revealing. In the
conscious canine model, some atypical antipsychotics cause
adiposity, including visceral obesity, a strong risk factor for
the metabolic syndrome. Furthermore, while few studies have
examined effects of antipsychotics on pancreatic b-cell function,
canine studies demonstrate that expected b-cell compensation for
insulin resistance may be reduced or even eliminated with these
Conclusions: Atypical antipsychotics have been
shown to contribute to weight gain, which may well reflect
increased body fat deposition. Such increased fat is known to
cause resistance to insulin action, although more information
regarding effect on insulin action is needed. The effect of these
drugs on fat distribution has been clearly shown in animal
models. It is known that the normal response to insulin
resistance is compensatory hyperinsulinemia, which may prevent
diabetes. In animals, there is evidence that the hyperinsulinemic
compensation is inadequate in the face of atypical antipsychotic
agents. It remains to be examined whether failure of adequate
pancreatic b-cell compensation for insulin resistance plays a
central role in the pathogenesis of diabetes associated with this
class of drugs.