Depressive disorders account for up to 80% of all psychiatric hospitalizations, and play a role in a substantial portion of hospital admissions in general.[1
] Individuals affected by depression are more likely to experience comorbidity with other medical conditions.[3
] Furthermore, depression is reported to increase the risk for suicide attempts and suicidal ideation by at least 4–6 fold.[4
] Besides the personal cost for afflicted individuals, which is often devastating, the total cost to society is immense. Identification of disease causing factors, along with new and more efficient treatment options, are therefore highly relevant.
Heritable factors have consistently been shown to play an important role in susceptibility to depressive disorders (for review, see[5
]), but little data exist regarding heritability of treatment response or adverse effects of medication. So far, few genetic predictors of treatment response or adverse events have been identified, and fewer still have been replicated consistently (for review, see[6
Over the past decades there has been an impressive increase in the availably of treatment options. A number of psychotherapies (talk-therapies, behavior therapies) and pharmacologic agents are now available to treat depression.[7
] However, today’s treatments are not curative. Clinical observations have shown that a substantial proportion of depressed patients will fail to respond to the first-line antidepressant treatment. Often, a second choice of treatment or addition of a second agent (augmentation) is needed to achieve response, and full remission of symptoms can be difficult to achieve quickly.[7
] Although most will eventually recover from the index episode, affected individuals often need a lifetime course of treatment to prevent recurrence. In addition, some reports raise the question of whether antidepressants can actually increase suicidal thinking or behavior in some patients.[12
In light of all this, clinicians encounter a very difficult task when treating patients suffering from depressive disorders. Which initial treatment should be used? If this fails, what is the next best choice? Is there a need for combination therapy? Which dosage and duration of treatment should be used for achievement of full functional recovery, while minimizing adverse events?[7
] Existing clinical data provide few answers, leading most clinicians to employ a trial-and-error strategy, albeit enhanced by their own clinical judgment. Genetic tests that help guide treatment decisions would be a great advance.
The general aim of the STAR*D study was to help the clinician with such difficult treatment decisions by elucidating which treatment options offer the greatest efficacy and tolerability. An important aim of the study was to identify alternative treatment strategies for the estimated two thirds of patients with major depression who do not achieve full remission after the initial treatment. Priority was given to identification of individual patient characteristics related to successful treatment outcomes in real-world clinical situations.
In addition, the STAR*D team joined forces with several teams of geneticists. While the approaches have varied, the goal of every team has been the identification of genetic markers of treatment outcome, including both remission and adverse events. Results from these efforts have been published in several reports[14
] and are summarized in this review.