Pharmacogenomics of drugs used to treat brain disorders

ABSTRACT Introduction Neuropsychiatric disorders (NPDs) (neurodevelopmental, mental, neurodegenerative, neurotoxic, complex disorders) are the third major problem of health in developed countries. About 10-20% of direct costs are attributed to pharmacological treatment; however, drug effectiveness is lower than 30% in most NPDs. Pharmacogenomics accounts for 60-90% variability in pharmacokinetics and pharmacodynamics. Areas covered Main areas covered include (i) organization of the pharmacogenetic machinery (pathogenic, mechanistic, metabolic, transporter, pleiotropic genes); (ii) pharmacogenomics of antidepressants, antipsychotics, anxiolytics, antiepileptics, anti-Alzheimer, anti-Parkinson, and anti-stroke drugs; and (iii) adverse drug reactions and pharmaco-resistance. Expert commentary The pharmacogenomics of NPDs is still primitive, but sufficient to help physicians to optimize pharmacological treatment by reducing ADRs (extrapyramidal symptoms, tardive dyskinesia, neurotoxicity, cerebrovascular damage) and unnecessary costs. Over 50% of psychotropic drugs are incorrectly prescribed. CYP enzymes participate in the metabolism of over 90% of drugs for the treatment of NPDs. Only 20% of the population is potentially extensive metabolizer for 80% of current psychotropic agents. Consequently, the introduction of pharmacogenomic procedures in the clinical setting is an urgent need for improving drug efficacy and safety.