Lithium Augmentation Compared With Phenelzine in Treatment-Resistant Depression in the Elderly: An Open, Randomized, Controlled Trial

Rob M. Kok, M.D.; Dagmar Vink, M.Sc.; Thea J. Heeren, M.D., Ph.D.; and Willem A. Nolen, M.D., Ph.D.

Background: Up to a third of elderly patients with major depressive disorder do not respond to a first course of treatment with an antidepressant. There is a lack of controlled studies evaluating therapies for treatment-resistant depression in late-life depression, and no randomized controlled studies assessing the efficacy and tolerability of lithium augmentation in elderly patients have been published.

Method: Twenty-nine elderly inpatients with major depressive disorder according to DSM-IV criteria who had previously failed to respond to 1 or more adequate trials with a tricyclic antidepressant or venlafaxine were included in a 6-week, open, randomized, controlled study with a 2-year follow-up. Subjects received either lithium augmentation or the monoamine oxidase inhibitor phenelzine. The primary outcome criterion was remission, defined as a final score of less than or equal to 10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Response was defined as at least 50% reduction on the MADRS or the Hamilton Rating Scale for Depression (HAM-D).

Results: Twenty-eight subjects completed the trial. Remission on the MADRS was achieved by 33.3% of the lithium patients, compared with none of the phenelzine patients (p = .042). Response also showed a difference in favor of lithium augmentation (p = .035 on both the MADRS and the HAM-D). Overall tolerability was good, with no dropouts due to side effects. Subjective memory impairment was more prevalent among patients receiving phenelzine (p = .002), and tremors were significantly more prevalent among patients receiving lithium (p = .002). During the 2-year follow-up, 25 patients (86.2%) did achieve remission, particularly on prolonging the lithium treatment (5 patients) or on lithium augmentation to phenelzine (5 patients).

Conclusion: Lithium was more effective than phenelzine in elderly patients with treatment-resistant major depressive disorder, while tolerance of both treatments was remarkably good in this group of elderly inpatients with many comorbid medical disorders.

Clinical Trials Registration: Controlled-trials.com identifier is rctn93105957.

(J Clin Psychiatry 2007;68:1177-1185)

Received June 29, 2006; accepted Dec. 20, 2006. From the Department of Old Age Psychiatry, Altrecht Institute of Mental Health Care, Utrecht (Dr. Kok); the Knowledge Centre of Psychiatry in the Elderly, Zeist (Ms. Vink); the Symfora Group Centres of Mental Health Care, Amersfoort, and University Medical Center Utrecht, Utrecht (Dr. Heeren); and the Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen (Dr. Nolen), The Netherlands.

Funding for this study was provided by The Netherlands Organization for Health Research and Development, The Hague, The Netherlands, grant number 1360.0001.

Dr. Kok has received research grants from Wyeth and Lundbeck and has received speaker's honoraria from GlaxoSmithKline, Lundbeck, Pfizer, and Wyeth. Dr. Heeren has received speaker's honoraria from Eli Lilly and Lundbeck. Dr. Nolen has received research grants from Astra Zeneca, Eli Lilly, GlaxoSmithKline, Wyeth, Netherlands Organization for Health Research and Development, Netherlands Organization for Scientific Research, and Stanley Medical Research Institute; has received speaker's honoraria from Astra Zeneca, Eli Lilly, Johnson & Johnson, Pfizer, Servier, and Wyeth; and has served on the advisory boards of Astra Zeneca, Cyberonics, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Pfizer, and Servier. Ms. Vink reports no other financial affiliations relevant to the subject of this article.

Corresponding author and reprints: Rob M. Kok, M.D., Altrecht Institute of Mental Health Care, Department of Old Age Psychiatry, Jutfaseweg 205, 3522 HR Utrecht, The Netherlands (e-mail: r.kok@altrecht.nl).