title: High-dose selegiline in treatment-resistant older depressive patients.
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.
authors.affiliation: Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda, Md.
authors.forename: T
authors.initials: T
authors.lastname: Sunderland
authors.forename: R M
authors.initials: RM
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Molchan
authors.forename: B A
authors.initials: BA
authors.lastname: Lawlor
authors.forename: A M
authors.initials: AM
authors.lastname: Mellow
authors.forename: P A
authors.initials: PA
authors.lastname: Newhouse
authors.forename: P N
authors.initials: PN
authors.lastname: Tariot
authors.forename: E A
authors.initials: EA
authors.lastname: Mueller
authors.forename: D L
authors.initials: DL
authors.lastname: Murphy
mesh_terms: D000367:Age Factors; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003866:Depressive Disorder / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012642:Selegiline / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D012642:Selegiline; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid