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Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).

The growing interest in incorporating pharmacogenetics (PGx) into drug development and clinical practice raises several questions: which study designs best reveal relevant pharmacogenetic biomarkers, best clarify specific hypotheses in PGx, and result in the largest gain of clinical evidence in this field? In this review, we present and compare a variety of PGx-related study designs. The type and quality of evidence gained by each category of study design is evaluated, and an appropriate timeline for the integration of pharmacogenetic studies into drug development is proposed. A summary of the pros and cons of the different study designs might help investigators decide how best to incorporate PGx into drug research. Using different scenarios to explain how genetic polymorphisms influence drug action, we illustrate how this knowledge can be translated into individualized drug choices, individualized dosage determination based on pharmacogenetic diagnostics, and other types of monitoring in order to make drug therapies safer and more effective.