Who Will Experience a Recurrence of Depression after Recovery?

Abstract & CommentarySynopsis: A total of 85% of patients who have recovered from an episode of major depression will suffer a recurrence of depression within 15 years. However, if a patient has remained in remission for at least five years, the rate of recurrence is reduced to 58%.

Source: Mueller TI, et al. Recurrence after recovery from major depressive disorder during 15 years of observational follow-up. Am J Psychiatry 1999;156:1000-1006.

It is well-known that major depression is an illness of recurrence. In addition, despite effective antidepressant and psychotherapeutic treatments, major depression remains an illness with high morbidity and mortality. Mueller and associates have compiled a large and impressive set of data to examine the rate of recurrence of major depression after recovery from the index episode. The present analysis is part of the "NIMH Collaborative Program on the Psychobiology of Depression," a large multi-center study looking at many aspects of depressive illness. The present study used standard rating instruments and was naturalistic, in that Mueller et al did not control the treatment the subjects received. For the present analysis, the authors identified 431 subjects with a major depressive episode. They excluded subjects who had bipolar or schizoaffective disorder or dysthymia. The main criteria for patients entering the study was a recovery from their index episode of major depression at some point during the 15-year follow-up period of the study. A total of 380 eligible subjects participated in the study. Of the 380 subjects described above, Mueller et al also examined a subgroup of 105 subjects who remained well for at least a 5-year period during the 15-year follow-up period.

The results of the study are striking and unfortunate. By the end of the 15-year follow-up period, 323 of the original 380 (85%) recovered subjects had suffered a recurrence of major depression. The news was somewhat better for the 105 subjects who had sustained at least a 5-year period of remission during the follow-up period. Specifically, 61 of these 105 (58%) subjects had a recurrence of major depression during the 15-year duration of the study. The authors attempted to correlate various clinical variables to the risk of recurrence. Factors at the index episode that predicted recurrence of depression included female sex, longer duration of index episode, never marrying, and multiple prior depressive episodes. The authors note that neither these nor any other factors predicted recurrence in subjects who had a sustained remission of depressive symptoms during the follow-up period. Few patients appeared to receive antidepressant medication for what is considered an adequate duration at an adequate dosage.

Comment by Andrew L. Stoll, MD

This important and possibly landmark study of the natural history of major depression underscores the importance of further research into the causes and treatments for major depression. It also points toward the inadequate application of otherwise effective treatments for major depression. Specifically, antidepressant medications, and to a lesser extent psychotherapy, can markedly reduce the rates of recurrence of depressive episodes. We need to better educate our patients and ourselves of the importance of maintenance therapy in major depression. Major depression is no different than hypertension, diabetes, and other medical illnesses that require close follow-up and adherence to effective therapies.