August 1994

High-Dose Selegiline in Treatment-Resistant Older Depressive Patients

Author Affiliations

From the Section on Geriatric Psychiatry, Laboratory of Clinical Science (Drs Sunderland, Molchan, and Murphy), and the Laboratory of Cerebral Metabolism (Dr Cohen), the National Institute of Mental Health, Bethesda, Md; the Department of Psychiatry, St James Hospital, Dublin, Ireland (Dr Lawlor); the Department of Psychiatry, University of Michigan, School of Medicine, Ann Arbor (Dr Mellow); the Department of Psychiatry, University of Vermont School of Medicine, Burlington (Dr Newhouse); the Department of Psychiatry, University of Rochester (NY) Medical Center (Dr Tariot); and Rutland (Vt) Community Mental Health Center (Dr Mueller).

Arch Gen Psychiatry. 1994;51(8):607-615. doi:10.1001/archpsyc.1994.03950080019003

Background:  We examined the effect of high-dose selegiline in 16 treatment-resistant older depressive patients. We hypothesized that selegiline, at a dosage of 60 mg/d, would be at least partially effective but that the higher doses would not maintain the monoamine oxidase B selectivity observed with the lower doses of selegiline.

Methods:  Sixteen treatment-resistant subjects (mean [±SD] age, 65.6±9.3 years) entered a double-blind, randomized, crossover study of placebo vs 3 weeks of selegiline at a dosage of 60 mg/d. Objective measures of mood and behavior were obtained in all subjects, and 10 of the subjects underwent repeated lumbar punctures for analysis of monoamine metabolites in the cerebrospinal fluid.

Results:  Objective measures of mood and behavior revealed significant improvement in the Hamilton Depression Rating Scale score (37.4% decrease), the Global Depression score (22.7% decrease), and the Brief Psychiatric Rating Scale score (19.3% decrease); subjective behavioral measures, however, did not show significant improvement during the 3-week medication trial. Cerebrospinal fluid values revealed a statistically significant drop in 3-methoxy-4-hydroxyphenylglycol (51%) and 5-hydroxyindoleacetic acid (17%) levels, and there was a significant lowering of systolic blood pressure on standing (15%), but these changes were not accompanied by clinical side effects.

Conclusions:  Our results suggest that high-dose selegiline can be an effective antidepressant in treatmentresistant older depressive patients. While the selegiline dose required has nonselective monoamine oxidase effects and thus would not be free of possible tyramine interactions, other advantages suggest that further investigations with selegiline are warranted in this population.