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National Institutes of Health

Science Update
November 1, 2006

Odds of Beating Depression Diminish as Additional Treatment Strategies are Needed

An overall assessment of the nation's largest real-world study of treatment-resistant depression suggests that a patient with persistent depression can get well after trying several treatment strategies, but his or her odds of beating the depression diminish as additional treatment strategies are needed. The conclusions from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, funded by NIMH, were published in the American Journal of Psychiatry on November 1, 2006.

The analysis also found two important indicators of treatment success. Those who become symptom-free have a better chance of remaining well, as measured in the follow-up period, than those who experience only symptom improvement. Those who need to undergo several treatment steps before they become symptom-free are more likely to experience a relapse during the one-year follow-up phase, reminding clinicians that even if a patient overcomes the depression, he or she still needs attention. These results underscore both the need for a better understanding of how different people respond to different depression treatments, and the challenges in finding broadly effective, short- and long-term depression treatments.

"This new STAR*D report reminds us that treating depression remains a formidable challenge," said NIMH Director Thomas Insel M.D. "While roughly two-thirds of patients report remission, many subsequently relapse. We need new treatments that are rapid, enduring, and individualized to facilitate recovery."

The paper examined all four medication levels of the STAR*D trial. About half of the participants became symptom-free after the first two treatment levels. After that, rates at which participants beat their depression slowed. Over the course of all four levels, about 70 percent of those who did not withdraw from the study became symptom-free.

Those who required more treatment levels tended to have more severe depressive symptoms, and more co-existing psychiatric and general medical problems at the beginning of the study than those who became well after just one treatment level. In addition, the rate at which participants withdrew from the study rose with each level—21 percent withdrew after level 1, 30 percent withdrew after level 2 and 42 percent withdrew after level 3.

"Clinicians need to pay particular attention to those patients with chronic depression and identify any co-existing conditions that may be exacerbating the depression or interfering with treatment," said lead author A. John Rush, M.D. of the University of Texas Southwestern Medical Center. "They need to closely monitor both the symptoms and side effects of these most vulnerable patients throughout treatment and suggest different treatment strategies when needed. Diligent follow-up, even after a patient becomes symptom-free, is essential to avoid relapse."

The STAR*D trial provides robust, real-world data that can be applied broadly to both primary and specialty care settings. The study confirms that different people respond to different treatment strategies, but it does not pinpoint what treatments work best for whom. The STAR*D team concluded that future research should be targeted to identify the best multi-step treatment options for individuals, especially those with treatment-resistant depression.

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg A, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Fava M. Acute and Longer-term Outcomes in Depressed Outpatients Who Required One or Several Treatment Steps: A STAR*D Report. American Journal of Psychiatry. 2006 Oct; 163(11):

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