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Lewis L. Judd, MD; Pamela J. Schettler, PhD; Hagop S. Akiskal, MD; William Coryell, MD; Andrew C. Leon, PhD; Jack D. Maser, PhD; David A. Solomon, MD

Arch Gen Psychiatry. 2008;65(4):386-394.

Context  Both bipolar disorder type I and type II are characterized by frequent affective episode relapse and/or recurrence. An increasingly important goal of therapy is reducing chronicity by preventing or delaying additional episodes.

Objectives  To determine whether the continued presence of subsyndromal residual symptoms during recovery from major affective episodes in bipolar disorder is associated with significantly faster episode recurrence than asymptomatic recovery and whether this is the strongest correlate of early episode recurrence among 13 variables examined.

Design  An ongoing prospective, naturalistic, and systematic 20-year follow-up investigation of mood disorders: the National Institute of Mental Health Collaborative Depression Study.

Setting  Five academic tertiary care centers.

Participants  Two hundred twenty-three participants with bipolar disorder (type I or II) were followed up prospectively for a median of 17 years (mean, 14.1 [SD, 6.2] years).

Main Outcome Measure  Participants defined as recovered by Research Diagnostic Criteria from their index major depressive episode and/or mania were divided into residual vs asymptomatic recovery groups and were compared according to the time to their next major affective episodes.

Results  Participants recovering with residual affective symptoms experienced subsequent major affective episodes more than 3 times faster than asymptomatic recoverers (hazard ratio, 3.36; 95% confidence interval, 2.25-4.98; P < .001). Recovery status was the strongest correlate of time to episode recurrence (P < .001), followed by a history of 3 or more affective episodes before intake (P = .007). No other variable examined was significantly associated with time to recurrence.

Conclusions  In bipolar disorder, residual symptoms after resolution of a major affective episode indicate that the individual is at significant risk for a rapid relapse and/or recurrence, suggesting that the illness is still active. Stable recovery in bipolar disorder is achieved only when asymptomatic status is achieved.

Author Affiliations: Department of Psychiatry, University of California, San Diego, San Diego (Drs Judd, Schettler, Akiskal, and Maser); Veterans Administration Hospital, San Diego, California (Dr Akiskal); Department of Psychiatry, University of Iowa College of Medicine, Iowa City (Dr Coryell); Weill Medical College of Cornell University, Ithaca, New York (Dr Leon); and Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, Rhode Island (Dr Solomon).

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