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Acute extrapyramidal side effects in haloperidol-treated patients with schizophrenia: no association with serotonergic 5-HT2A and 5-HT2C receptor gene polymorphisms

Literature data suggest that both dopaminergic and serotonergic system and their receptors are involved in the development of extrapyramidal side effects (EPS) in schizophrenic patients treated with first generation antipsychotic drug like haloperidol. There are limited data that gene variants of serotonergic 5-HT2A and 5-HT2C receptor could be the risk factors for the incidence of EPS. The aim of the study was to determine 5-HT2A and 5-HT2C receptor gene polymorphisms and the occurrence of EPS in schizophrenic patients (DSM-IV criteria) after 2 weeks monotherapy with haloperidol (15 mg/day). The hypothesis was that there is a genetic predisposition for the development of EPS after acute treatment with haloperidol. The severity of EPS was evaluated using Simpson Angus Rating Scale for Extrapyramidal Side Effects, Barnes Akathisia Rating Scale and Extrapyramidal Symptom Rating Scale. Genomic DNA was extracted from whole blood and genotyping of 5-HT2A (102T/C ; rs6313) and 5-HT2C (-759C/T ; rs3813929) receptors was performed using TaqMan based commercial kits. After treatment with haloperidol, 60% of patients developed EPS. Akathisia, acute dystonia and dyskinesia were observed in 29%, 21% and 44% of patients, respectively. There was no significant difference in genotype and allele frequencies of 5-HT2A or 5-HT2C polymorphisms between patients with or without EPS and their particular symptoms. The results did not confirm the hypothesis that 5-HT2A and 5-HT2C variants might be the risk factors for haloperidol-induced EPS in schizophrenic patients. Additional genetic studies and haplotype analysis are necessary to determine the role of serotonergic system and its genes in development of EPS.

extrapyramidal side effects; schizophrenia; haloperidol; gene variants of serotonergic 5-HT2A and 5-HT2C receptors

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