Applying Pharmacogenomics in Drug Therapy of Neurologic and Psychiatric Disorders

Significant variabilities in therapeutic responses to drugs for psychiatric and neurological disorders have long been a challenge for clinicians. This likely is secondary to the heterogenous nature of both illnesses, imprecise understanding of the disease pathophysiology, lack of valid biological markers, and the traditional trial-and-error approach, especially for psychotropics, in selecting appropriate medications and determining optimal dosage regimens. Over the last three decades, numerous pharmacogenomic studies based on candidate gene or genome-wide associations have identified some potential benefits as well as limitations for several genetic variants in predicting psychotropic treatment responses. The role of individual genetic profile to predict drug response is even less explored for neurodegenerative diseases. Current evidence suggest that usefulness of genotyping with molecular diagnostics is likely restricted to predicting adverse drug effects and possibly increasing medication adherence in subsets of populations. The promise of translating gene-based drug targets into treatment-based genetic stratification for optimal therapy remains mostly elusive, In addition, debates continue regarding the cost-effectiveness of genotyping and the most appropriate way of evaluating cost-benefits. This article presents an overview of the impact of genetic factors on treatment response in select psychiatric and neurological disorders, with antidepressants and mood stabilizers, antipsychotics, as well as anti-epileptic and anti-parkinsonian agents as examples.