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A Randomized Controlled Trial in Patients Older Than 59 Years

Charles F. Reynolds III, MD; Ellen Frank, PhD; James M. Perel, PhD; Stanley D. Imber, PhD; Cleon Cornes, MD; Mark D. Miller, MD; Sati Mazumdar, PhD; Patricia R. Houck, MSH; Mary Amanda Dew, PhD; Jacqueline A. Stack, MSN; Bruce G. Pollock, MD, PhD; David J. Kupfer, MD

JAMA. 1999;281:39-45.

Context  Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability.

Objective  To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years.

Design  A 2x2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist.

Setting  University-based psychiatric research clinic.

Patients  Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged 70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions.

Interventions  Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n=24); medication clinic with placebo (n=29); monthly maintenance IPT with placebo (n=21); and monthly maintenance IPT with nortriptyline (n=22).

Main Outcome Measure  Recurrence of major depressive episode.

Results  The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43% (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald ²=3.56; P=.06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years.

Conclusion  In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.

Author Affiliations: The Mental Health Clinical Research Centers for Late- and Mid-Life Mood Disorders, Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pa.

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