Metabolic Disorders in Schizophrenia

Table 1.

Drug	Weight Gain	Risk for Diabetes	Worsening Lipid Profile
Clozapine	+++	+	+
Olanzapine	+++	+	+
Risperidone	++	0	0
Quetiapine	++	0	0
Aripiprazole*	±	-	-
Ziprasidone*	±	-	-

Table 1. Second-Generation Antipsychotics and Metabolic Abnormalities

+ = increase effect
- = no effect
0 = discrepant results
* = newer drugs with limited long-term data
Copyright ©2004 American Diabetes Association
From Diabetes Care. Vol 27, 2004:596-601. Reprinted with permission from The American Diabetes Association

Table 2.

	Baseline	4 Weeks	8 Weeks	12 Weeks	Quarterly	Annually	Every 5 Years
Personal/ family history	X					X
Weight (BMI)	X	X	X	X	X
Waist circumference	X					X
Blood pressure	X			X		X
Fasting plasma glucose	X			X		X
Fasting lipid profile	X			X			X

Table 2. Monitoring Protocol for Patients on Atypical Antipsychotics*

BMI = body mass index
*More frequent assessments may be warranted based on clinical status.
Copyright ©2004 American Diabetes Association
From Diabetes Care. Vol 27, 2004:596-601. Reprinted with permission from The American Diabetes Association

Raphael T, Parsons JP. Blood sugar studies in dementia praecox and manic depressive insanity. Arch Neurol Psychiatry. 1921;5:681-709.
Lorenz WF. Sugar tolerance in dementia praecox and other mental disorders. Arch Neurol Psychiatry. 1922;8:184-196.
Kohen D. Diabetes mellitus and schizophrenia: historical perspective. Br J Psychiatry Suppl. 2004;47:S64-66. Abstract
Mukherjee S, Decina P, Bocola V, et al. Diabetes in schizophrenic patients. Compr Psychiatry. 1996;37:68-73. Abstract
Nasrallah HA. A review of the effect of atypical antipsychotics on weight. Psychoneuroendocrinology. 2003;28:83-96.
Thakore JH, Mann JN, Vlahos I, Martin A, Reznek R. Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia. Int J Obes Relat Metab Disord. 2002;26:137-141. Abstract
Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode drug-naive patients with schizophrenia. Am J Psychiatry. 2003;160:284-289. Abstract
Weiser M, Reichenberg A, Grotto I, et al. Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study. Am J Psychiatry. 2004;161:1219-1223. Abstract
Mokdad A, Serdula M, Dietz B, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidemic in the U.S. JAMA. 1999;282:1519-1522. Abstract
Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2002;288:1723-1727. Abstract
Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156:1686-1696. Abstract
Czobor P, Volavka J, Sheitman B, et al. Antipsychotic-induced weight gain and therapeutic response: a differential association. J Clin Psychopharmacol. 2002;22:244-251. Abstract
Simpson MM, Goetz RR, Devlin MJ, Goetz SA, Walsh BT. Weight gain and antipsychotic medication: differences between antipsychotic-free and treatment periods. J Clin Psychiatry. 2001;62:694-700. Abstract
Bobes J, Rejas J, Garcia-Garcia M, et al. Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study. Schizophr Res. 2003;62:77-88. Abstract
Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002;63:856-865. Abstract
Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics. J Clin Psychiatry. 2003;64:598-604. Abstract
Harris MI. Diabetes in America: epidemiology and the scope of the problem. Diabetes Care. 1998;21(suppl 3):C11-C14. Abstract
Thonnard-Neumann E. Phenothiazines and diabetes in hospitalized women. Am J Psychiatry. 1968;124:978-982. Abstract
Jori A, Carrara MC. On the mechanism of the hyperglycemic effect of chlorpromazine. J Pharm Pharmacol. 1966;18:623-624. Abstract
Schwartz L, Munoz R. Blood sugar in patients treated with chlorpromazine. Am J Psychiatry. 1968;125:253-255. Abstract
Koller EA, Doraiswamy PM. Olanzapine-associated diabetes mellitus. Pharmacotherapy. 2002;22:841-852. Abstract
Koller E, Schneider B, Bennett K, Dubitsky G. Clozapine-associated diabetes. Am J Med. 2001;111:716-723. Abstract
Koller EA, Cross JT, Doraiswamy PM, Schneider BS. Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy. 2003;23:735-744. Abstract
Avella J, Wetli CV, Wilson JC, Katz M, Hahn T. Fatal olanzapine-induced hyperglycemic ketoacidosis. Am J Forensic Med Pathol. 2004;25:172-175. Abstract
Newcomer JW, Haupt DW, Fucetola R, et al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002;59:337-345. Abstract
Koro CE, Fedder DO, L'Italien GJ, et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002;325:243.
FDA MedWatch Safety Alert - Abilify (aripiprazole). Available at: http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm#abilify. Accessed July 13, 2004.
FDA MedWatch Safety Alert - Seroquel (quetiapine fumarate). Available at: http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm#seroquel. Accessed July 13, 2004.
FDA MedWatch Safety Alert - Clozaril (clozapine). Available at: http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm#clozaril. Accessed July 13, 2004.
FDA MedWatch Safety Alert - Zyprexa (olanzapine). Available at: http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm#zyprexa. Accessed July 13, 2004.
Stroup TS, McEvoy JP, Swartz MS, et al. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull. 2003;29:15-31. Abstract
American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care. 2004;27:596-601. Abstract

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Introduction

Even prior to the introduction of neuroleptic medications in the 1950s, there was evidence that individuals with schizophrenia suffered from a variety of medical and metabolic disorders at rates higher than the general population. Investigators in the early 1900s observed that patients with dementia praecox had increased rates of abnormal glucose tolerance tests,^[1-3] and more recent studies have found an increased rate of type 2 diabetes in schizophrenic patients compared with the general population.^[4] Studies have shown that first-episode, never-medicated schizophrenia patients have increased visceral adiposity,^[5,6] impaired fasting glucose tolerance, and are more insulin resistant than healthy comparison controls.^[7] Other factors such as increased smoking,^[8] sedentary lifestyle, and lack of self care increase the risk even further. Therefore, due to a confluence of health and lifestyle factors, individuals with schizophrenia are at high risk for a variety of untoward health consequences.

Although the introduction of the atypical neuroleptics has resulted in significant clinical advances, several of these agents have a variety of significant metabolic health risks associated with them. Concern for these side effects recently prompted the US Food and Drug Administration (FDA) to issue a warning for all of the atypical neuroleptics, indicating that hyperglycemia and diabetes may result from the atypical neuroleptics. Although the warning was for all of the currently available medications, there is substantial evidence indicating that some of the agents place the individual at a greater risk than others. The clinician should therefore carefully consider the ethical and health risks associated with psychopharmacologic interventions, utilizing first those agents that maximize clinical response while minimizing health risks in the already vulnerable individual.

Page 1 of 6

Antipsychotics and Weight Gain

References

Table 1.

Table 2.

Metabolic Disorders in Schizophrenia: Relationship to Atypical Antipsychotic Treatment

Introduction

Table of Contents

Table 1.

Table 2.

References

Faculty and Disclosures

Metabolic Disorders in Schizophrenia: Relationship to Atypical Antipsychotic Treatment

Introduction

Table of Contents