HIGH-DOSE SELEGILINE IN TREATMENT-RESISTANT OLDER DEPRESSIVE PATIENTS

Background: We examined the effect of high-dose selegiline in 16 treat ment-resistant older depressive patients. We hypothesized that selegil ine, 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 sele ctivity observed with the lower doses of selegiline. Methods: Sixteen treatment-resistant subjects (mean [+/-SD] age, 65.6+/-9.3 years) ente red 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 b ehavior were obtained in all subjects, and 10 of the subjects underwen t repeated lumbar punctures for analysis of monoamine metabolites in t he cerebrospinal fluid.Results: Objective measures of mood and behavio r revealed significant improvement in the Hamilton Depression Rating S cale score (37.4% decrease), the Global Depression score (22.7% decrea se), and the Brief Psychiatric Rating Scale score (19.3% decrease); su bjective behavioral measures, however, did not show significant improv ement during the 3-week medication trial. Cerebrospinal fluid values r evealed a statistically significant drop in 3-methoxy-4-hydroxyphenylg lycol (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. Concl usions: Our results suggest that high-dose selegiline can be an effect ive antidepressant in treatment-resistant older depressive patients. W hile the selegiline dose required has nonselective monoamine oxidase e ffects and thus would not be free of possible tyramine interactions, o ther advantages suggest that further investigations with selegiline ar e warranted in this population.