Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly: an open, randomized, controlled trial.
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.


METHODS
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).


CONCLUSIONS
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.


BACKGROUND
Controlled-trials.com identifier is RCTN93105957.
Kok
Rob M
RM
Department of Old Age Psychiatry, Altrecht Institute of Mental Health Care, Utrecht, The Netherlands. r.kok@altrecht.nl
Vink
Dagmar
D
Heeren
Thea J
TJ
Nolen
Willem A
WA
D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage; D003511:Cyclohexanols / Q000008:administration & dosage; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018020:Lithium Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010624:Phenelzine / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D018020:Lithium Compounds; D000069470:Venlafaxine Hydrochloride; D010624:Phenelzine