Is There a Role for Antidepressant and Antipsychotic Pharmacogenetics in Clinical Practice in 2014?

The recent release of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, has been associated with much hand-wringing and many comments about the lack of progress on the understanding of biological mechanisms underlying mental disorders and their treatment.1 Publications, both in the general press and in scientific journals, decried psychiatry for being falsely advertised as a science. Among many similar examples, a columnist in The New York Times stated,The problem is that the behavorial sciences like psychiatry are not really sciences; they are semi-sciences. [ . . . ] Mental diseases are not really understood the way, say, liver diseases are understood, as a pathology of the body and its tissues and cells.2He went on, quoting Martin Seligman, a past president of the American Psychological Association, in this statement:I have found that drugs and therapy offer disappointingly little additional help for the mentally ill than they did 25 years ago-despite billions of dollars in funding.This viewpoint, by the general public and by health professionals, is that the impact of scientific progress in psychiatry has not met up with its promise. Contemporary psychiatric treatments are as efficacious as (or more efficacious than) most other nonsurgical treatments offered by modern medicine. With a number-needed-to-treat typically of 3 to 6, the efficacy of antidepressants (ADs) and antipsychotics (APs) is superior or similar to the efficacy of any medications used to treat general medical conditions except for antibiotics.3 Nevertheless, it can be argued that, except for better tolerability, there has been only incremental progress in the development of newer ADs and APs since the original, serendipitous discoveries of iproniazid, imipramine, and chlorpromazine in the 1950s.There are many possible reasons for this negative perception regarding progress in psychiatry, including a bias about patients with mental illness. Because of their salience, people are painfully aware of those who are not treated or are not doing well, and they are not aware of those who are successfully treated and are doing well; we see and hear the untreated, acutely psychotic shoeless man screaming in the street or our loved ones who have not yet responded to their medications. By contrast, the mental illnesses of our colleagues or friends who have remitted with treatment are invisible. Another reason for these negative perceptions is that, when used under usual care conditions, psychotropics typically yield mediocre, or even poor, outcomes. For instance, several studies published during the past decade have shown that less than one-half of depressed patients who were treated under usual care conditions by a community psychiatrist or a family physician achieved good outcomes.4,5Some of these disappointing outcomes are due to the variable efficacy and the early side effects of ADs and APs. Given the tepid faith in the therapeutic powers of these medications, patients and health professionals are unable or unwilling to stay the course in the face of delays in response or unpleasant side effects, leading to premature discontinuation and, consequently, perceived lack of benefit. Innovative models of care incorporating more intensive education and support for patients, health professionals, and family caregivers (for example, collaborative care for major depressive disorder or assertive community treatment for schizophrenia) can counteract these factors and markedly increase the number of patients who take, tolerate, and respond to psychotropics.5 A complementary approach that could increase the number of patients who take and stay the course with currently available psychotropics is to preferentially use medications that are better tolerated. This can be done either by implementing medication algorithms that promote the systematic use of psychotropics that are statistically more likely to be better tolerated (that is, medications with lower overall rates of discontinuation associated with adverse effects) or by trying to match specific patients with specific medications. …

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