Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes.
OBJECTIVE
Melatonin, the hormone produced nocturnally by the pineal gland, serves as a circadian time cue and sleep-anticipating signal in humans. With age, melatonin production declines and the prevalence of sleep disorders, particularly insomnia, increases. The efficacy and safety of a prolonged release melatonin formulation (PR-melatonin; Circadin* 2 mg) were examined in insomnia patients aged 55 years and older.


METHODS
Randomised, double blind, placebo-controlled.


METHODS
Primary care.


METHODS
From 1248 patients pre-screened and 523 attending visit 1, 354 males and females aged 55-80 years were admitted to the study, 177 to active medication and 177 to placebo. The study was conducted by primary care physicians in the West of Scotland and consisted of a 2-week, single blind, placebo run-in period followed by a 3-week double blind treatment period with PR-melatonin or placebo, one tablet per day at 2 hours before bedtime.


METHODS
Responder rate (concomitant improvement in sleep quality and morning alertness on Leeds Sleep Evaluation Questionnaire [LSEQ]), other LSEQ assessments, Pittsburgh Sleep Quality Index (PSQI) global score, other PSQI assessments, Quality of Night and Quality of Day derived from a diary, Clinical Global Improvement scale (CGI) score and quality of life (WHO-5 well being index).


RESULTS
Of the 354 patients entering the active phase of the study, 20 failed to complete visit 3 (eight PR-melatonin; 12 Placebo). The principal reasons for drop-out were patient decision and lost to follow-up. Significant differences in favour of PR-melatonin vs. placebo treatment were found in concomitant and clinically relevant improvements in quality of sleep and morning alertness, demonstrated by responder analysis (26% vs. 15%; p = 0.014) as well as on each of these parameters separately. A significant and clinically relevant shortening of sleep latency to the same extent as most frequently used sleep medications was also found (-24.3 vs.-12.9 minutes; p = 0.028). Quality of life also improved significantly (p = 0.034).


CONCLUSIONS
PR-melatonin results in significant and clinically meaningful improvements in sleep quality, morning alertness, sleep onset latency and quality of life in primary insomnia patients aged 55 years and over.


BACKGROUND
The trial was conducted prior to registration being introduced.
Wade
Alan G
AG
CPS Research, Glasgow, UK. alangwade@fastmail.fm
Ford
Ian
I
Crawford
Gordon
G
McMahon
Alex D
AD
Nir
Tali
T
Laudon
Moshe
M
Zisapel
Nava
N
D000368:Aged; D000369:Aged, 80 and over; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology
D003692:Delayed-Action Preparations; D010919:Placebos; D008550:Melatonin