Pharmacoepigenetics in schizophrenia: Predicting drug response

Abstract

Individual differences in treatment response in schizophrenia pose a significant challenge in the management of the disease, due to several biological as well as psychosocial factors, including genetic and epigenetic mechanisms. Pharmacoepigenetics investigates how epigenetic mechanisms affect the variability in effectiveness of treatments and adverse side effects. Antipsychotics such as clozapine (atypical) and haloperidol (typical) directly induce epigenetic changes by altering DNA methyltransferases and histone acetyltransferases, while indirectly affecting neuroinflammatory and stress response pathways. Personalized medicine using epigenetic markers (DNA methylation, non-coding RNAs including microRNAs and long non-coding RNAs) holds great promise for improving the drug response and reducing the side effects of antipsychotic treatment. These developments could revolutionize the treatment of schizophrenia by addressing the complexities involved in responding to treatment. However, ethical and technical barriers to implementing strategies based on epigenetic regulation in clinical practice are fundamental challenges that need to be carefully addressed in this field. This review examined the epigenetic mechanisms involved in the efficacy of antipsychotic drugs.

Keywords: Antipsychotic drugs; Personalized medicine; Pharmacoepigenetics; Schizophrenia; Treatment failures.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart illustrating the selection process of studies included in this review.