Decrease of Energy Expenditure Causes Weight Increase in Olanzapine Treatment - A Case Study

The aim of this study was to evaluate the mechanisms underlying weight gain induced by the atypical antipsychotic, olanzapine. We performed euglycemic, hyperinsulinemic clamp combined with indirect calorimetry on a 48-year-old male with antisocial personality disorder, alcohol dependence and paranoid ideation before and after one month of olanzapine (10 - 15 mg/day) therapy. The patient gave his informed, written consent for this study. The results were a weight gain of 6 kg and a decrease in both basal (from 1673 to 1613 kcal/24 h) and 3-hour (from 22.8 to 20.2 cal/kg fat free mass/min) energy expenditure. Serum thyroid hormone and high-density lipoprotein cholesterol levels decreased, and the triglyceride and low-density lipoprotein cholesterol levels increased. Insulin sensitivity did not change. We conclude that decreased basal energy expenditure may contribute to weight gain in olanzapine treatment.

References

• 1 Conley R R, Meltzer H Y. Adverse events related to olanzapine.  J Clin Psychiatry. 2000;  61 (8) 26-29
• 2 Allison D B, Mentore J L, Heo M, Chandler L P, Cappelleri J C, Infante M C, Weiden P J. Antipsychotic-induced weight gain: a comprehensive research synthesis.  Am J Psychiatry. l999;  156 1686-1696
• 3 Taylor D M, McAskill R. Atypical antipsychotics and weight gain-a systematic review.  Acta Psychiatr Scand. 2000;  101 416-432
• 4 Wirshing D A, Spellberg B J, Erhart S M, Marder S R, Wirshing W C. Novel antipsychotics and new onset diabetes.  Biol Psychiatry. 1998;  44 778-783
• 5 Lindenmayer J P, Patel R. Olanzapine-induced ketoacidosis with diabetes mellitus.  Am J Psychiatry. 1999;  156 1471
• 6 Devlin M J, Yanovski S Z. Obesity: What mental health professionals need to know.  Am J Psychiatry. 2000;  157 854-866
• 7 DeFronzo R A. Glucose intolerance and aging: Evidence for tissue insensitivity to insulin.  Diabetes. l979;  28 1091-1111
• 8 Franssila-Kallunki A, Schalin-Jäntti C, Groop L. Effect of gender on insulin resistance associated with aging.  Am J Physiol. 1992;  263 (Endocrinol Metab 26) E780-E785
• 9 Ferrannini E. The theoretical basis for indirect calorimetry: a review.  Metabolism. 1988;  37 287-301
• 10 Merilainen P T. Metabolic monitor.  Inst I Clin Comput. 1987;  4 167-177
• 11 Franssila-Kallunki A. Energy metabolism in insulin resistant states. Academic Dissertation, Helsinki University. Helsinki Yliopistopaino 1994
• 12 Tappy L, Owen O E, Boden G. Effects of hyperinsulinemia on urea pool size and substrate oxidation rates.  Diabetes. 1988;  17 1212-1216
• 13 Franssila-Kallunki A, Groop L. Factors associated with basal metabolic rate in patients with type 2 (non-insulin dependent) diabetes mellitus.  Diabetologia. 1992;  35 962-966
• 14 Baptista T. Body weight gain induced by antipsychotic drugs: mechanisms and management.  Acta Psychiatr Scand. 1999;  100 3-16
• 15 Kraus T, Haack M, Schuld A, Hinze-Selch D, Kuhn M, Uhr M, Pollmacher T. Body weight and leptin plasma levels during treatment with antipsychotic drugs.  Am J Psychiatry. 1999;  156 312-314
• 16 Herran A, Garcia-Unzueta M T, Amado J A, de la Maza M T, Alvarez C, Vazquez-Barquero J L. Effects of long-term treatment with antipsychotics on serum leptin levels.  Br J Psychiatry. 2001;  179 59-62