Metabolic syndrome induced by conventional and atypical antipsychotics

Written by Kun Imre Zoltán, Szántó Zsuzsanna, Kun Ildikó, Kolcsár Melinda

In the development of drug-induced obesity and metabolic syndrome (MS), the neuropsychotropic medications have an important role, especially the antipsychotics (AP), some antidepressants, mood stabilizers and anticonvulsants. The underlying diseases for which these drugs are used, also increase the susceptibility to obesity and MS. The long-term treatment, and some side effects (e.g., sedation, facilitating the sedentarism, their metabolic actions) may also predispose to weight gain. The MS appears as whole or partial form, depending on the degree of the insulin resistance. Among the conventional AP, the haloperidol can induce a moderate weight gain. The atypical AP (AAP), especially clozapine and olanzapine usually provoke obesity and MS, while ziprasidone, aripiprazole and asenapine are so called “weight neutral”, or cause only a slight weight gain. Between the above mentioned groups are situated risperidone, paliperidone, amisulpride, quetiapine, iloperidone, presenting moderate metabolic risk. Nonetheless, the FDA (Food and Drug Administration) requires drawing attention “diabetes warning” for every AAP. The weight gain is determined primarily by enhancing the appetite through the hypothalamic appetite regulation centers, mainly by blocking of H1 histamine and 5HT2C serotonin receptors; the inhibition of D2- and D3-dopamine-receptors may also contribute. The blockade of M3-muscarine- and 5HT1A-receptors situated on β-pancreatic cells may cause an abrupt fall of insulin secretion, which very rarely, can induce a potentially fatal diabetic ketoacidosis, or hyperglycaemic hyperosmolar state. Recently a new mechanism through receptor-X was hypothesized that induces rapidly hypertriglyceridemia, and consequently insulin resistance and hyperinsulinism, with or without weight gain. Independently from MS, some antipsychotics can induce prolonged QT-syndrome which can result in life-threatening polymorphic ventricular tachyarrhythmia. Besides the central pathogenic mechanisms, the study also highlights the role of the peripheral, fat tissue factors participating in the development of MS, namely the influence of some AP on adipokine secretions and transcription factors affecting adipogenesis. 

 

Keywords: antipsychotics, metabolic syndrome, central and peripheral mechanisms, blocking of H1-, 5HT2C-, D2-, D3- and M3-receptors, adipogenesis


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