Recurrence after recovery from major depressive disorder during 15 years of observational follow-up

Am J Psychiatry. 1999 Jul;156(7):1000-6. doi: 10.1176/ajp.156.7.1000.


Objective: The recurrence of an affective disorder in people who initially recover from major depressive disorder was characterized by using the unique longitudinal prospective follow-up data from the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies.

Method: Up to 15 years of prospective follow-up data on the course of major depressive disorder were available for 380 subjects who recovered from an index episode of major depressive disorder and for 105 subjects who subsequently remained well for at least 5 years after recovery. Baseline demographic and clinical characteristics were examined as predictors of recurrence of an affective disorder. The authors also examined naturalistically applied antidepressant therapy.

Results: A cumulative proportion of 85% (Kaplan-Meier estimate) of the 380 recovered subjects experienced a recurrence, as did 58% (Kaplan-Meier estimate) of those who remained well for at least 5 years. Female sex, a longer depressive episode before intake, more prior episodes, and never marrying were significant predictors of a recurrence. None of these or any other characteristic persisted as a predictor of recurrence in subjects who recovered and were subsequently well for at least 5 years. Subjects reported receiving low levels of antidepressant treatment during the index episode, which further decreased in amount and extent during the well interval.

Conclusions: Few baseline demographic or clinical characteristics predict who will or will not experience a recurrence of an affective disorder after recovery from an index episode of major depressive disorder, even in persons with lengthy well intervals. Naturalistically applied levels of antidepressant treatment are well below those shown effective in maintenance pharmacotherapy studies.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Combined Modality Therapy
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy
  • Depressive Disorder / therapy*
  • Electroconvulsive Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Imipramine / therapeutic use
  • Longitudinal Studies
  • Male
  • National Institute of Mental Health (U.S.)
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Recurrence
  • Survival Analysis
  • Treatment Outcome
  • United States


  • Antidepressive Agents
  • Imipramine