Study Finds Complete Symptom Resolution Reduces Risk of Depression Recurrence

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People who have had an episode of major depression are at high risk for having another episode. Now, researchers at University of California, San Diego School of Medicine have found that the risk of recurrence is significantly lower for people with complete, rather than partial depressive symptom resolution.

The findings, published online October 27 in the Journal of Clinical Psychiatry, point to the need to redefine clinically what constitutes the end of a major depressive episode (MDE). It also suggests changes in the management of depression treatment may be needed, said first author Lewis L. Judd, MD, Mary Gilman Marston Professor and Distinguished Professor in the Department of Psychiatry.

Judd said current clinical consensus defines the end of an MDE as eight consecutive weeks with “no more than minimal” residual symptoms. The definition includes two distinct levels of depressive symptom resolution: “asymptomatic recovery” (with no depressive symptoms) and “residual symptom resolution” of MDE (with some continuing mild symptoms). In their study, the researchers compared the two levels in terms of time to a future depressive episode and other key clinical outcomes.

The researchers analyzed data from 322 patients diagnosed with MDE who entered the National Institute of Mental Health Collaborative Depression Study from 1978 to 1981 and were followed for up to 31 years. Of those patients, 61.2 percent recovered asymptomatically from their diagnosed MDE. Judd said the research team found that this group remained free of a depressive episode relapse or recurrence 4.2 times longer than those who still had residual symptoms (a median of 135 weeks versus 32 weeks). Retaining residual symptoms was associated with a nearly three times higher risk of returning to a full-blown depressive episode within one year (74 percent versus 26 percent). The residual symptom group also had a greater depressive illness burden during the next 10 or 20 years, and more long-term difficulty with work and household functioning and with personal relationships.

For physicians, Judd said the findings indicate that patient treatment should continue until depressive symptoms are completely resolved. “If you treat a major depressive episode until there are no remaining symptoms, the individual is likely to enter a stable state of wellness and be free of depression for months or even years.” Conversely, he said treatment should not be ended just because the patient has improved. “As long as they have any residual symptoms, they are still ill and at high risk for relapse.”

The authors also found that the very large difference in the length of time that the groups stayed well was not due to differences in the level of antidepressant treatment received. In addition, the level of symptom resolution was more important than any of 18 other predictors (suggested in the literature) regarding the length of time that subjects stay free of a depressive episode.

Judd said the findings provide the first research-based assessment of how to define the end of an MDE, in terms of both symptom state and necessary duration. As to the length of the asymptomatic period needed to define MDE recovery, the researchers found that four consecutive weeks at the asymptomatic status was virtually as strong an indicator of stable recovery as eight weeks.

Based on the study findings, the authors conclude that four weeks completely free of depressive symptoms should be the new definition of recovery from a major depressive episode and the goal of treatment.

Co-authors include Pamela J. Schettler, UCSD; A. John Rush, Duke-National University of Singapore; William H. Coryell, Carver College of Medicine, Iowa City, Iowa; Jess G. Fiedorowicz, Carver College of Medicine and the University of Iowa; David A. Solomon, Brown University School of Medicine.

This research was funded, in part, by a National Institutes of Health (grant MH 025416).