engleski

Serotonergic system and side effects of antipsychotic medication

The treatment of schizophrenia is associated with high prevalence of relapse and discontinuation of therapy. Although first-generation (FGA) and second-generation (SGA) antipsychotics are effective in the treatment of positive symptoms, they differ in adverse effect profile. Acute or chronic extrapyramidal symptoms (EPS) appear frequently in patients treated with FGA (phenotiazines, butyrophenones) while side effects such as metabolic syndrome (MetSy) are associated with the treatment with SGA (clozapine, olanzapine, risperidone). The unlike side effects of antipsychotics could be associated with their different main molecular targets, dopaminergic D2 (for FGA and SGA), or serotonergic 5-HT2A receptors (for SGA). FGA and SGA are both antagonists of D2, but in contrast to tight blockade of D2 by FGA, the binding of SGA to DRD2 does not last long enough to induce EPS. Although the EPS are mostly related to the dopaminergic system, pharmacological studies suggest the connection between antipsychotics, their side effects and serotonergic system, probably through serotonergic receptors or by serotonin effect on dopamine release in the dopaminergic pathways. Despite intensive research, the association between genetic variability of serotonin receptors and the development of MetSy after SGA medication is unclear. The few studies with a small number of patients suggest that the C allele of HTR2A (102T/C) and the C allele of HTR2C (-759C/T) polymorphisms could be the risk factors for the development of MetSy in schizophrenia. Additional studies are necessary to evaluate the role of serotonin, serotonin-dopamine signaling pathways and their genes in the development of EPS and MetSy in patients during treatment with antipsychotics.

Serotonergic receptors; side effects; antipsychotics

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