pdf). The key lesson of the past decade of clinical trials is the heterogeneity of psychiatric diagnoses. Diagnostic categories, such as schizophrenia, depression, or autism, though each defined by a broader set of observed

symptoms, may individually comprise different biological entities with distinct pathophysiologies, requiring different treatments. What we need now are medications for targeted subgroups of patients within diagnostic categories who share biology, not just symptoms. This is the essence of personalized medicine or what has recently been called “precision medicine” (Committee on a Framework for Developing a New Taxonomy of Disease, 2011). Personalized medicine overlaps (Figure 1) with what is coming to be known as “genomic this website medicine,” which uses information from a patient’s genome for diagnosis, prognosis, and treatment planning, emphasizing uncommon or unique aspects of each patient (for review, see Feero et al., 2010). Emphasis on the unique aspects of a patient is, in fact, nothing new for psychiatry. Effective psychiatric care has always been challenging, in part, precisely because it has always been personalized. Every unhappy family may indeed be unhappy in its own way. That is why we need a much

larger variety of treatments, each with a much narrower range of indications. Traditional pharmacogenetics and genomics are forerunners of genomic medicine that use genetic methods to better Selleck Bortezomib match patients with treatments. The focus is on genetic markers that correlate with treatment response or adverse events. Unlike clinical trials, which emphasize homogeneity of outcomes, pharmacogenetic studies emphasize heterogeneity. As such, the goal is to maximize efficacy while minimizing adverse events. Genetic variation can affect how individuals handle medications in a variety of ways, ranging from absorption to toxicity, all in the context of other individual variables, found such as treatment adherence (Figure 2). Despite this complexity, several pharmacogenetic success stories have emerged in recent years. A few

are highlighted here to illustrate how genetics can help to reduce toxicity and adverse events—traditional aims of pharmacogenomics—but also help to identify subgroups of patients with distinct pathophysiology that may be uniquely responsive to particular medications. A set of common genetic variants accounts for up to 40% of the variance in optimal dosage of warfarin, a common anticoagulant (for review, see Carlquist and Anderson, 2011). This discovery has garnered much attention, because bleeding complications from warfarin are not rare and can be serious. In 2010, the FDA revised warfarin labeling to include dosage guidelines based on genotype—a first. However, it is not yet clear that the genetic tests bring additional clinical utility beyond what can be done by skillful monitoring of standard blood clotting assays, such as the INR.