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The Pharmacogenetics of Major Depression: Past, Present, and Future

  • Gonzalo Laje
    Affiliations
    Genetic Basis of Mood and Anxiety Disorders Unit, Mood and Anxiety Program, National Institute of Mental Health, Bethesda, Maryland.
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  • Francis J. McMahon
    Correspondence
    Address reprint requests to Francis J. McMahon, M.D., 35 Convent Drive, Room 1A202, Bethesda, MD 20892-3719
    Affiliations
    Genetic Basis of Mood and Anxiety Disorders Unit, Mood and Anxiety Program, National Institute of Mental Health, Bethesda, Maryland.
    Search for articles by this author
      Much has been said and written in recent years about the promise of pharmacogenetics. The vision is one of a world where we will be able to match medications with patients, maximizing efficacy while minimizing—or eliminating—adverse effects. This vision has been widely embraced out of a real desire to better help patients. But we are now some years into the pharmacogenetics enterprise, and we are beginning to accumulate real-world data in juxtaposition to our perhaps somewhat idealistic expectations. Some of the assumptions underlying the vision are beginning to be scrutinized more closely. Can we really match medications with patients when the range of available treatments is still quite small compared with the range of clinical presentations? Can genetics really provide the keys? How much of the difference between patients in efficacy and adverse effects will actually be attributable to differences in life experience and circumstances that we can neither measure biologically nor address medically? The technological advances of human genetics over the past decade, along with the recent availability of large treatment cohorts for study, are beginning to answer these questions. Pharmacogenetics is being transformed from a small field of promising leads into one of the foundations of evidence-based medicine. Few specialties stand to benefit as much as psychiatry, where all of our treatment options are empirical and the matching of patients with treatments is largely a question of clinical judgment.
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