Dr. Trivedi and Colleagues Reply

To the Editor: Dr. Hierholzer highlights the importance of conducting effectiveness studies using antidepressants in “real world” settings that include subjects who reflect the patient population treated in routine clinical practice, including patients with most axis I and axis III comorbidities. We, undoubtedly, agree with the necessity of conducting treatment studies with clinical practice subjects in order to provide a readily applicable set of findings for treating physicians. Furthermore, the modest remission rates found in our study highlight the need for diligently delivered treatments using the measurement-based care approach, which emphasizes the routine measurement of symptoms and side effects by ratings instruments. The STAR*D study results not only have immediate clinical relevance but also provide a more realistic set of expectations for outcomes for major depression, thus emphasizing the timeliness of such a study.

We also agree with the distinctions between efficacy trial results and the more modest remission rates observed with the first-step antidepressant in the STAR*D study. It has become clear from a number of recent effectiveness trials that remission from depression is not as common as previously thought and that the course of treatment and the low rates of remission and sustained benefit emphasize the chronic, recurrent, and treatment-resistant nature of major depressive disorder (1 – 3) . We also agree that the results raise the question of whether more aggressive treatments, used either alone or in combination, should be employed earlier in the course of treatment.

In terms of assisting clinicians in tailoring treatment for individual patients, of particular note are the results from this phase of the STAR*D study that identify a number of predictors, including being well-educated, employed, married, white, and female, with few complicating problems associated with a better antidepressant response. Factors associated with a poorer response included co-occurring anxiety, substance abuse or general medical conditions, and poorer quality of life.

Initial results from the STAR*D report also emphasize the need to carefully study sequential treatments with currently available antidepressants using innovative study designs in “real world” settings that enhance transfer-of-knowledge to treating clinicians. Successful implementation of measurement-based care in clinical practice also provides a metric to gauge patient progress. Finally, results from subsequent steps in STAR*D will provide guidance concerning the “true” rate of treatment resistance for treatments currently available.