Psychotropic Medications: Optimal Prescribing Through the Utilization of Genetic Testing

Abstract

Psychiatric drug treatment is characterized by large interindividual differences in drug response and dosage requirements. Interindividual variability in drug response can be a major clinical problem and may lead to discontinuation of potentially efficacious medications. Research suggests that individual variability in CYP enzyme activity is an important reason for drug therapy failure. The most substantial variability in medication metabolism is due to genetic polymorphisms. The polymorphisms present in most CYP genes, are responsible for a substantial part of this variability. Research has found that four CYP phenotypes can be identified: poor (slow) metabolizers (PM); intermediate metabolizers (IM); extensive metabolizers (EM); and the ultra-rapid metabolizers (UM), who have multiple gene copies. The ultra-rapid metabolizer (UM) phenotype is recognized as a cause of therapeutic inefficacy of antidepressant (due to resulting low serum levels), whereas an increased risk of toxicity and side effects has been reported in poor (slow) metabolizers (PMs) with several psychotropics (desipramine, venlafaxine, amitriptyline, haloperidol). Based on a review of the literature, it is reasonable to assume that some individuals will metabolize relevant drugs too quickly (and perhaps be nonresponders) and others may metabolize medications too slowly and become toxic and symptomatic. These groups perhaps represent individuals who would benefit most from the genetic testing. Despite cost and inconvenience of testing, these individuals may benefit.