The Antidepressants and the Metabolic Syndrome

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Abstract

The relationship between antidepressants (AD) and metabolic syndrome (MS) can be approached from many perspectives. We can start from the mutuality of depression and MS: depression often causes MS and vice versa; however, the two diseases aggravate each other. Altered glucocorticoid secretion - among others - may be a common etiological factor for depression and MS. Enhanced glucocorticoid production leads both to sleep disorders and insulin resistance, and several antidepressants cause obesity and insulin resistance. In addition, sympathetic nervous system activity increases in depression, together with the elevated production of counter-insulin hormones such as catecholamines (adrenaline) and glucocorticoids. From the components of MS, body weight changes can be most easily followed by the patient. The obesogenic mechanisms of AD drugs are different. The H1-receptor blocking agents have the most important weight gaining effect, followed by the 5-HT2c-receptor blocking and/or down-regulating ADs. The fattening effect of mirtazapine, paroxetine, and tricyclic antidepressants are based on such central mechanisms. Blocking of alpha1-receptors contributes to the obesogenic effects of certain drugs by inducing sedation: this has been confirmed in case of imipramine, amitriptyline, and doxepin. Fluoxetine behaves differently depending on the dose and duration of treatment: while at the usual doses it induces weight loss at the beginning of therapy, its initial anorexigenic effects reverses during prolonged use; while its activation effect at high doses is favorable in bulimia. The selective noradrenaline reuptake inhibitor reboxetine reduces appetite, similarly to bupropion, which inhibits dopamine reuptake as well. We highlight the effect of fluoxetine on direct adipogenicity, mentioning its preadipocyteadipocyte transformation-reducing and adipocyte proliferation-inhibiting activity, as well as its ability to enhance fat cell autophagy.

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