Acute Insulin Response and {beta}-Cell Compensation in Normal Subjects Treated With Olanzapine or Risperidone for 2 Weeks: Response to Hardy et al.

doi:10.2337/dc07-0314

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Online Letters: Comments and Responses
Online Letters

Acute Insulin Response and ß-Cell Compensation in Normal Subjects Treated With Olanzapine or Risperidone for 2 Weeks

Response to Hardy et al.

Ripu D. Jindal, MD

From the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Address correspondence to Ripu D. Jindal, MD, 3811 O'Hara St., Pittsburgh, PA 15213. E-mail: jindalr{at}upmc.edu

Hardy et al. (1) demonstrate that administration of olanzapineor risperidone does not impair acute insulin response and concludethat their results argue against substantial and generalizedimpairment of insulin action secretion with these agents aftershort-term treatment. An earlier study by Ader et al. (2) suggestedthat olanzapine impairs insulin sensitivity as well as compensatoryincrease in insulin secretion. Hardy et al. (1) acknowledgethat the shorter duration of olanzapine administration may havecontributed to their failure to detect a decrease in insulinsecretion. There are other differences in the designs of thetwo studies. In the study by Hardy et al. (1), healthy humanvolunteers received 5 mg/day olanzapine for 4 days followedby 10 mg/day olanzapine for 11–13 days. In the study byAder et al. (2), dogs were administered 15 mg/day olanzapineand as a proportion of body weight seem to have received a muchlarger dosage of olanzapine. The dosage of olanzapine in thestudy by Hardy et al. (1) was also less than what is commonlyused clinically. For example, in the recent landmark study,Clinical Antipsychotic Trials of Intervention Effectiveness(3), mean modal dosage for olanzapine was 20.1 mg/day.

Participants in the study by Hardy et al. (1) were given isocaloricdiet with the instruction to continue with the same diet duringoff-site passes, whereas dogs in the other study were fed adlibitum.

The results of the study by Hardy et al. (1) are also inconsistentwith the results of another study (4) in which patients withschizophrenia exhibited a reduction in insulin secretion following2-week treatment with 10 mg/day olanzapine. The participantswere admitted to an inpatient facility for diet stabilizationwith an isocaloric diet and then requested to maintain thisdiet (4). Insulin secretion was quantified from intravenousglucose tolerance test.

In light of the discrepancy in the results of these studies,longer-term prospective studies employing clinically meaningfuldosages are needed to better understand the effect of olanzapineon insulin secretion.

References

Hardy TA, Meyers AL, Yu J, Shankar SS, Steinberg HO, Porksen NK: Acute insulin response and ß-cell compensation in normal subjects treated with olanzapine or risperidone for 2 weeks. Diabetes Care 30:157–158, 2007[Free Full Text]
Ader M, Kim SP, Catalano KJ, Ionut V, Hucking K, Richey JM, Kabir M, Bergman RN: Metabolic dysregulation with atypical antipsychotics occurs in the absence of underlying disease: a placebo-controlled study of olanzapine and risperidone in dogs. Diabetes 54:862–871, 2005[Abstract/Free Full Text]
Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223, 2005[Abstract/Free Full Text]
Chiu CC, Chen KP, Liu HC, Lu ML: The early effect of olanzapine and risperidone on insulin secretion in atypical-naive schizophrenic patients. J Clin Psychopharmacol 26:504–507, 2006[Medline]