Pharmacodynamic targets of psychotic patients treated with a long-acting therapy

Abstract

Introduction

Given the poor compliance of schizofrenic patients to antipsychotic therapies, are been developed drugs in long-acting formulation that for their pharmacokinetic ensures prolonged therapeutic activities. Currently, we consider that their efficacy depends on hereditary tracts, influencing both pharmacodynamic and pharmacokinetic parameters.

Objective

Investigate relationships between clinical efficacy and genetic polymorphims of long-acting drugs’ pharmacodynamic targets.

Methods

Seventy-eight psychotic patients, treated with atypical long-acting antipsychotics (olanzapine pamoate, paliperidone palmitate, risperidon and aripiprazole), were examined. We carried out a blood sampling to evaluate dopaminergic DRD2 and glutamatergic GRM3 genetic receptors polymorphisms. PANSS and BPRS scales were used to assess clinical condition.

Results

Regarding the GRM3 genes, the study of rs2228595 and rs6465084 polymorphisms showed a prevalence of wild type genotypic frequency of 81.2% and 56.2%, respectively. The prevalence of the patients with mutated heterozygote genotype (rs6465084 polymorphisms) resulted high (40.6%). Considering rs1989796 e rs274622 polymorphisms, the sample showed a prevalence of mutated heterozygote genotype in the 53.1% e 45.3%, respectively, with a percentage of 43.7% of patients with a mutation in homozygosis. Considering the rs146812 polymorphism, the 53.1% of patients resulted with a wild type genotype. Finally, findings showed a prevalence of 56.2% for the mutated heterozygote genotype in the DRD2 rs6277 polymorphism. The genotypic categorization analysis demonstrated a significative association between the GRM3 rs274622 polymorphism and higher BPRS scores.

Conclusions

The relationship between rs274622 polymorphism and worse clinical conditions could indicate a major resistance to long-acting antipsychotics in patients with genotypic frequency CT (mutated heterozygosis) for this polymorphism.

Disclosure of interest

The authors have not supplied their declaration of competing interest.