Lithium Augmentation Compared With Phenelzine in Treatment-Resistant Depression in the Elderly

Department of Old Age Psychiatry, Altrecht Institute of Mental Health Care, Utrecht, The Netherlands.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 09/2007; 68(8):1177-85. DOI: 10.4088/JCP.v68n0803
Source: PubMed


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.
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).
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).
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. identifier is RCTN93105957.

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Available from: Rob Kok, Nov 26, 2015
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    • "In contradiction, one suicide has been reported in the lithium treatment group within a double-blind period and one suicide in an open-label phase of a 12-month randomized double-blind controlled clinical trial comparing olanzapine versus lithium in the maintenance treatment of bipolar disorder (Tohen et al. 2005). A study Kok et al. 2007 comparing the effect of lithium augmentation with phenelzine among patients with treatment-resistant major depressive disorder reported two deaths in the lithium group (n = 15) while using nortriptyline . In the phenelzine group (n = 14), one patient died taking phenelzine who took lithium a few months after finishing the trial and two other patients died while continuing use of phenelzine. "
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