Second-Generation Antipsychotic Exposure and Metabolic-Related Disorders in Patients With Schizophrenia

Abstract

Patients with schizophrenia are at increased risk for cardiovascular disease as a consequence of lifestyle habits, impaired access to health care, and, increasingly, due to metabolic side effects ostensibly attributed to second-generation antipsychotics (SGAs). There is little evidence, however, on the extent and temporal patterns of SGA-associated metabolic side effects. We longitudinally examined the differential prevalence rates of obesity, diabetes mellitus, and diabetic ketoacidosis among inpatients with schizophrenia compared with control inpatients without schizophrenia. The data were derived from the National Inpatient Sample, the largest all-payer inpatient care database in the United States consisting of 5 to 8 million inpatient hospital stays per year sampled to approximate a 20% sample of community hospitals from 1988 to 2002. Overlaid on these observations was the market penetration data for SGAs. In 1988, the net difference from controls in obesity prevalence among inpatients with schizophrenia was +4.7%; by 2002, this difference had widened to +14.7%. Similarly, a significant increase in net prevalence of diabetes mellitus and diabetic ketoacidosis was observed from 1988 to 2002 among schizophrenic inpatients. In conclusion, after the introduction of SGAs, patients with schizophrenia in the United States have experienced a striking net increase in the prevalence of obesity and diabetes mellitus. This is likely to significantly add to an already elevated risk for cardiovascular disease in this population. Further investigations are urgently required so that health policy can be appropriately amended for preventive measures.

Metabolic Consequences of Antipsychotic Therapy: Preclinical and Clinical Perspectives on Diabetes, Diabetic Ketoacidosis, and Obesity

“…When the liberation of ketone bodies resulting in a low blood pH (ketoacidosis) is combined with glucose-induced osmotic diuresis, which depletes blood of potassium and sodium, it sets up a self-perpetuating, cycle of ionic dysregulation and dehydration that can lead to coma and death. Although DKA is rare, the use of atypical antipsychotic drugs is believed to have increased its incidence (Henderson 2001;Jin et al 2002;Wilson et al 2003;Reist et al 2007). …”

Drug-Induced Dyslipidemia

“…However, they are increasingly recognized to cause weight gain and lead to the metabolic syndrome [200][201][202][203][204]. Weight gain due to increased appetite may be mediated by the combined blockade of H1 histamine and serotonin 2C receptors on the hypothalamic neurons regulating feeding behavior [205,206].…”

Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect

“…Индекс массы тела рассчитывается как отношение массы тела к квадрату роста (кг/м 2 ); значения, лежащие в диапазоне 18,5-24,9 кг/м 2 , считаются нормальными, индекс массы тела -25,0-29,9 кг/м 2 считается избыточным, свыше 30 кг/м 2 позволяет диагностировать ожирение [10]. Установлено, что прием антипсихотиков второго поколения у 50-80% пациентов вызыва-ют 10%-ю прибавку в весе за счет жировой ткани [11]. Многочисленными исследованиями установ-лено, что прием клозапина и оланзапина вызы-вает наибольшую прибавку в весе, затем следует рисперидон, наиболее безопасными в ýтом от-ношении являются зипрасидон и арипипразол [12].…”