Major depressive disorder: A prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse

Lewis L. Judd, Hagop S. Akiskal, Jack D. Maser, Pamela J. Zeller, Jean Endicott, William Coryell, Martin P. Paulus, Jelena L. Kunovac, Andrew C. Leon, Timothy I. Mueller, John A. Rice, Martin B. Keller

Research output: Contribution to journalArticlepeer-review

579 Scopus citations


Background: The study tested whether level of recovery from major depressive episodes (MDEs) predicts duration of recovery in unipolar major depressive disorder (MDD) patients. Methods: MDD patients seeking treatment at five academic centers were followed naturalistically for 10 years or longer. Patients were divided on the basis of intake MDE recovery into residual depressive symptoms (SSD; N = 82) and asymptomatic (N = 155) recovery groups. They were compared on time to first episode relapse/recurrence, antidepressant medication, and comorbid mental disorders. Recovery level was also compared to prior history of recurrent MDEs (> 4 lifetime episodes) as a predictor of relapse/recurrence. Results: Residual SSD compared to asymptomatic recovery patients relapsed to their next MDE > 3 times faster (median = 68 vs. 23 weeks) and to any depressive episode > 5 times faster (median = 33 vs. 184 weeks). Residual SSD recovery status was significantly associated with early episode relapse (OR = 3.65) and was stronger than history of recurrent MDEs (OR = 1.64). Rapid relapse in the SSD group could not be attributed to higher comorbidity or lower antidepressant treatment. Limitations: Although inter-rater agreement on weekly depressive symptom ratings was very high (ICC > 0.88), some error may exist in assigning recovery levels. Antidepressant treatments were recorded, but were not controlled. Conclusions: MDE recovery is a powerful predictor of time to episode relapse/recurrence. Residual SSD recovery is associated with very rapid episode relapse which supports the idea that SSD is an active state of illness. Asymptomatic recovery is associated with prolonged delay in episode recurrence. These findings of this present study have important implications for the goals of treatment of MDD and for defining true MDE recovery.

Original languageEnglish
Pages (from-to)97-108
Number of pages12
JournalJournal of affective disorders
Issue number2-3
StatePublished - Sep 1 1998


  • MDE recovery
  • Rapid episode relapse
  • Residual symptoms


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