title: A double blind-placebo controlled study on melatonin efficacy to reduce anxiolytic benzodiazepine use in the elderly.
abstract: OBJECTIVE
  The present double blind-placebo controlled study was carried out to assess whether melatonin (3 mg p.o., fast release form) could be useful to reduce benzodiazepine dosage in old patients with minor sleep disturbance. The possible correlation of urinary excretion of 6-sulphatoxymelatonin (aMT6s) before starting treatment and outcome of treatment was also examined.
  
  
  METHODS
  Forty-five patients (36 females, 70.5 +/- 13.1 years old) regularly taking anxiolytic benzodiazepines in low doses were studied. Overall quality of morning freshness, daily alertness, sleep quality, and sleep onset and offset time were assessed from structured clinical interviews and from logs completed by the patients. Patients were randomized to receive either melatonin or placebo for 6 weeks. On day 14 of treatment, benzodiazepine dose was reduced by half and on day 28, it was halted. No significant modifications of sleep or wakefulness were detected after benzodiazepine withdrawal. As compared to basal, there was a general lack of changes in quality of wakefulness or sleep in patients taking melatonin or placebo. Sleep quality of patients taking melatonin during the first two weeks of treatment was significantly lower than that of placebo. Melatonin advanced sleep onset by 27.9 +/- 11.9 min and decreased significantly the variability of sleep onset time (p= 0.03). The urinary concentration of aMT6s prior to the study did not correlate with any parameter examined.
  
  
  CONCLUSIONS
  The present study does not support melatonin efficacy to reduce the use of benzodiazepines in low doses. This contrasted with the demonstrable effectiveness of melatonin to reduce benzodiazepine consumption in insomniac patients when used in hypnotic amounts.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Buenos Aires, Argentina. cardinal@mail.retina.ar
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cardinali
authors.forename: Elisa
authors.initials: E
authors.lastname: Gvozdenovich
authors.forename: Marcos R
authors.initials: MR
authors.lastname: Kaplan
authors.forename: Isidoro
authors.initials: I
authors.lastname: Fainstein
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Shifis
authors.forename: Santiago
authors.initials: S
authors.lastname: Pérez Lloret
authors.forename: Liliana
authors.initials: L
authors.lastname: Albornoz
authors.forename: Armando
authors.initials: A
authors.lastname: Negri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008550:Melatonin / Q000627:therapeutic use*; D008875:Middle Aged; D012890:Sleep / Q000187:drug effects; D017211:Treatment Failure; D014851:Wakefulness / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D008550:Melatonin