The Metabolic Syndrome During Atypical Antipsychotic Drug Treatment: Mechanisms and Management

Abstract

The frequency of obesity, insulin resistance, type 2 diabetes mellitus and other components of metabolic syndrome appear to be significantly elevated in some psychiatric patients. This is a notable example of genetic/environment interaction. Considering the genetic contribution, evidence of insulin resistance in persons with schizophrenia was reported in the pre-pharmacological era. High insulin, glucose, and cortisol levels are observed in first episode psychosis. The frequency of type 2 diabetes mellitus is significantly increased in persons with schizophrenia and bipolar disorder and in their first-degree relatives. Finally, a link exists between schizophrenia and enzymes involved in glycolysis and between antipsychotic drug-induced weight gain and serotonin receptor polymorphism. Important environmental factors are poor dietary habits, smoking, lack of physical exercise, and drug treatment, mostly with antipsychotic drugs (APDs) and perhaps with mood stabilizers. The APDs probably induce metabolic dysfunction by producing sudden appetite increase and weight gain in predisposed subjects. However, direct drug effects on glucose and lipid metabolism independent from body weight change have been proposed. Excessive weight gain is mainly observed with clozapine, olanzapine, chlorpromazine, and thioridazine and is less consistently noted with risperidone or quetiapine. Two recently introduced APDs, ziprasidone and aripiprazole, display a neutral effect on weight and metabolism. Subjects at high risk must be identified early during APD treatment so that provide lifestyle counseling and pharmacological assistance can be provided. The immediate research agenda for the APDs is to improve the animal models of drug-induced metabolic dysfunction; to clarify mechanisms other than weight gain and appetite stimulation; and to test pharmacological agents in randomized, double-blind studies to prevent or reverse metabolic syndrome in selected patients.

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

“…Long-term ziprasidone treatment is associated with weight gain . There are also concerns of increased risk of metabolic syndrome -characterized by obesity, insulin resistance, hypertension, and dyslipidaemia -with atypical antipsychotics (Baptista et al 2004). It is important to be aware, however, that adverse events occurring during maintenance treatment may differ from those observed in patients treated with agents for the first time.…”

Diabetes and Cardiovascular Care Among People with Severe Mental Illness: A Literature Review

“…43 Proposed mechanisms for antipsychotic-induced weight gain and other metabolic effects include activity at the D2 receptor, antagonism (or inverse agonism) at 5HT2C, antagonism at 5HT2A serotonin receptors, antagonism at alpha (1A) adrenergic receptors and especially antagonism at histamine (H1) receptors. 11,12,[44][45][46][47] Weight gain has long been associated with centrally active drugs with high affinity for the H1 receptor, with H1 antagonism known to increase feeding and sedation. 48,49 These combined mechanisms suggest that weight gain during antipsychotic treatment may be related to alterations in satiety signaling leading to increased energy intake, and increases in sedation leading to reduced energy expenditure.…”

“…[5][6][7] This mortality gap represents a formidable health care disparity, leading to calls by the Surgeon General and the Institute of Medicine for increased public health attention in this area. 8,9 Secondgeneration antipsychotic medications (SGAs) contribute to this CVD risk [10][11][12] and dominate the US antipsychotic medication market. 13,14 …”

Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

“…[1][2][3][4][5][6][7][8] Particular emphasis has been placed on characterizing the elevated frequency of MS among patients with BD 4,9 and the postulated role of psychotropic medication in its development and maintenance. 6,7,10,11 Even though a genetically-based predisposition to metabolic dysfunction in BD has been consistently suggested, 12 few studies have evaluated metabolic status in relatives of patients with BD. Such studies might help clarify the role of environmental and genetic factors in the development of MS and related disorders in subjects with BD.…”