High-dose selegiline in
treatment-resistant older depressive patients
Sunderland T, Cohen RM, Molchan S, Lawlor BA, Mellow AM,
Newhouse PA, Tariot PN, Mueller EA, Murphy DL
Section on Geriatric Psychiatry,
National Institute of Mental Health,
Bethesda, Md.
Arch Gen Psychiatry 1994 Aug; 51(8):607-15
ABSTRACT
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
treatment-resistant 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.
