STAR* D represents a 7-year effort by literally hundreds of people and thousands of patients. Future reports will 1) compare longer-term outcomes of the various randomized treatments (eg, does cognitive therapy prevent relapse better than medication as either a switch or augmentation strategy?); 2) identify which patients benefit from which treatments (eg, do different patients [defined by different clinical features or genetic polymorphisms] respond differently to different treatments?); and 3) determine whether different treatment sequences (in steps 1 to 4) are preferred for some but not other patients (1). At this point, however, we can ask,“What have we learned so far?” This highly representative clinical sample of depressed outpatients has revealed that major depression is often chronic, severe, and associated with substantial general medical and psychiatric comorbidity. Two-thirds of patients had at least one concurrent general medical condition; two-thirds had at least one other psychiatric disorder; nearly 40% had their first depressive episode before age 18; over half reported a mood disorder in at least one first-degree relative; and over half met criteria for anxious features (2, 3). In addition, patients in primary care and psychiatric settings with major depression did not differ clinically except for slightly higher rates of general medical conditions in primary care settings, and slightly higher rates of prior suicide attempts in psychiatric settings (4). In terms of treatment tactics, STAR* D developed and implemented easily applied methods to enhance the quality of care in both daily practice and in clinical trials in representative groups of patients. This so-called “measurement-based care” entailed the routine use of simple paper-and-pencil symptom and side effect measures at each treatment visit, along with guidance based on these measures to recommend timely dose or treatment changes. A likely consequence of this high-quality, consistent care was that outcomes in primary care and psychiatric settings were not different (5). Longer times than expected were needed to reach response or remission. In fact, onethird of those who ultimately responded did so after 6 weeks (and half of those who ultimately remitted did so after 6 weeks)(5). These results suggest that stopping a vigorously dosed treatment for patients who report little benefit by 6 weeks is ill-advised. Itemized symptom measures (as opposed to a global judgment) might well detect a benefit (eg, 25%–45% reduction in baseline symptom severity) that many patients may not report if asked for their global impression. If a modest improvement (eg,≥ 20% reduction) is present, a dose increase (if tolerated) at 6 weeks or simply further exposure (up to 10 weeks) may help a sizable number of patients to at least respond, if not achieve remission, by 12 weeks.

As for treatment strategies, we found that patients had clear preferences about their acceptance of augmentation versus switching at both the second and third levels in STAR* D (6). Those who fared better in the prior step and who evidenced minimal intolerance preferred augmentation, while those with little benefit or substantial intolerance with the prior treatment preferred to switch. Whether augmentation is best even if the initial treatment is minimally effective could not be evaluated in the STAR* D design. As for specific medications at the second step, results suggest that either a withinclass switch (eg, citalopram to sertraline) or an out-of-class switch (eg, citalopram to bupropion-SR) is effective, as was a switch to a dual-action agent (eg, venlafaxine-XR). While bupropion-SR and buspirone were not different as augmentation options in the