College of Psychiatric and Neurologic Pharmacists

Objectives: To compare the prevalence and health care costs of metabolic conditions in patients with bipolar disorder to age- and sex-matched control patients using a large insurance claims database.
Methods: A retrospective analysis of medical service and prescription claims from the Thomson Reuters (Healthcare) MarketScan Commercial Database (which includes claims information on >12 million employees with employer-based insurance and their dependents in the United States) was conducted. Claims data for 28,531 patients with bipolar disorder were compared for 1 year with data for 85,593 age- and sex-matched control patients with no mental health disorders and no psychotropic medication use.
Results: Patients with bipolar disorder had a significantly higher prevalence of metabolic comorbidities than the general population (37% vs 30%, P < 0.0001), and annual medical service treatment costs for metabolic conditions were twice that of the control cohort ($531 vs $233, P < 0.0001). The bipolar cohort had significantly higher overall medical service and prescription drug costs than those of the control cohort ($12,764 vs $3,140, P < 0.0001). Prescription medication costs for metabolic conditions were higher as well, with bipolar cohort per-patient costs of $571 versus $301 for the control cohort (P < 0.0001).
Conclusions: Patients with bipolar disorder have significantly more metabolic comorbidities and higher medical costs than age- and sex-matched controls. Studies that link claims data with medical records or primary data collection pertaining to metabolic conditions may overcome limitations in the diagnostic information and outcome predictors. To reduce the medical and economic burden of bipolar disorder, strategies should be identified to prevent the development of metabolic comorbidities and improve medication adherence.
(C) 2009 Lippincott Williams & Wilkins, Inc.

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Effectiveness of Medications Used to Attenuate Antipsychotic-Related Weight Gain and Metabolic Abnormalities: A Systematic Review and Meta-Analysis

Neuropsychopharmacology 35,
1520 (June 2010). doi:10.1038/npp.2010.21

Authors: Lawrence Maayan, Julia Vakhrusheva
& Christoph U Correll

Keywords: Clinical Pharmacology/Trials; Eating/Metabolic Disorders; Metformin; Psychopharmacology; Schizophrenia/Antipsychotics; Sibutramine; Topiramate; Weight Gain; Weight Loss

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Switching to a different second-generation antipsychotic (SGA) with a lower risk of weight gain is recommended for overweight or obese psychiatric patients undergoing SGA treatment. However, there have been no complete reports regarding the long-term metabolic effects of switching to amisulpride. In this open-label 1-year study, we investigated the effects on body weight and other metabolic profiles when psychiatric patients treated with another SGA were switched to amisulpride treatment. Forty-six schizophrenia or schizoaffective inpatients with a body mass index greater than 27 kg/m2 were enrolled in the switch group. These patients were cross-titrated to amisulpride treatment and followed up for 1 year prospectively. Another 46 inpatients matched with the baseline body mass index of those in the switch group were enrolled as the control group retrospectively. The results showed that the switch group had greater weight loss than the control group (7.80 +/- 6.67 vs 2.60 +/- 6.23 kg, respectively; repeated-measure analysis of variance, P < 0.0005). During the treatment course, the amisulpride-treated patients showed significantly decreased fasting triglyceride, total cholesterol, glucose, and insulin resistance levels; decreased diastolic blood pressure and pulse rate; and a significant increase in high-density lipoprotein cholesterol levels after switching to amisulpride (all with a P < 0.05). The prevalence of metabolic syndrome in amisulpride-treated patients also decreased significantly from 65.2% to 30.4% (McNemar test, P < 0.0005). These findings suggest that switching to amisulpride could be an effective treatment of overweight or obese psychiatric patients treated previously with other SGAs.
(C) 2009 Lippincott Williams & Wilkins, Inc.

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The aim of this study was to model in mice the association between metabolic syndrome and the administration of atypical antipsychotic (AAP). Two dosages (4 and 8 mg/kg per day) of olanzapine (OL) were infused in 36 female mice for 30 days by osmotic mini-pumps. This study was also designed to further extend the implications raised in other experiments by our model of AAP-induced metabolic dysregulation. Through the use of the osmotic mini-pumps, this model is aimed to circumvent the shorter (than in humans) half-life of AAPs in rodents and to chronically administer OL by a reliable and less disturbing method. Indirect calorimetry was used to evaluate metabolic rate (MR) and respiratory exchange ratio together with weight and caloric intake. Serum insulin, leptin, and glucose tolerance (oral glucose tolerance test) were assessed. Pancreatic beta cells insulin levels, periuterine and liver fat content were also analyzed. Olanzapine-infused mice exhibited a reduction of overall MR (kilojoule per hour) and resting MR and respiratory exchange ratio, with periuterine fat significantly enlarged. All metabolic alterations were detected at the highest dose, with major effects found on weight gain and hyperphagia. Impaired glucose metabolism, associated with hyperinsulinemia and hyperleptinemia were found. Insulin resistance was evidenced by the raise of HOMA-IR index. Increased insulin and lipid storage were detected at pancreatic and hepatic levels respectively. These findings illustrate the development of a cluster of risk factors (metabolic syndrome) and, for the first time, a decrease of energy expenditure (MR) due to chronic OL infusion.
(C) 2009 Lippincott Williams & Wilkins, Inc.

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