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#120 Melatonin for sleep: Exhausted by other options?


CLINICAL QUESTION
QUESTION CLINIQUE
Is melatonin effective for sleep disorders?


BOTTOM LINE
RÉSULTAT FINAL
The quality of melatonin research is generally poor and at high risk of bias. If the results are believable, melatonin may help people fall asleep faster (~10 minutes) and spend more time asleep (~15 minutes)both of these amounts may be of limited clinical value.  



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EVIDENCE
DONNÉES PROBANTES
Six systematic reviews with seven meta-analyses,1-6 included 9-19 randomized controlled trials (RCTs) with 279-1683 patients.1-6 Another systematic review7 duplicated two others.3,4 
  • Falling asleep faster: four of six meta-analyses statistically significant.1-5 
    • Overall: 4-11.7 minutes sooner.1,3,5 
    • “Sleep onset disorder” patients: 23 minutes sooner.2  
  • Increasing total sleep time: four of six meta-analyses statistically significant.1-5 
    • Overall: 8.2-18.2 minutes more.1,4  
  • Improving sleep quality:  
    • Perceived sleep qualitystandard mean difference=0.22 (0.12-0.32) improvement1 (of marginal clinical significance). 
    • Sleep efficiency (time asleep while in bed): two of four meta-analyses statistically significant.3-5 
      • Improved 1.9%-2.2%.4,5  
  • Jet lag/shift workers: significantly improved total sleep time, 18.2 minutes (8.1 to 29.3), but other outcomes (sleep onset, quality) not improved.4 
  • Short-term adverse events: no difference in any including headache, dizziness, nausea, or drowsiness.3,4,7 Long-term unknown. 
  • Issues include small studies (averaging only 20-30 patients per RCT),2-5 short duration (many one day,5 most <4 weeks1-5,7), inconsistent results in RCTs,1,3-5,7 low quality (example <25% have concealed randomization),3,4 subjective reporting of sleep (up to ~40% of RCTs use diaries),1 use of rating scale without clinical meaning (subjective jet lag).6 
Context: 
  • Melatonin has inconsistent dose-effect relationship between 0.3-5mg.1,3,5-7 
    • As a result, the “recommended dose” is 0.3-5mg.8 
  • Melatonin typically taken:  
    • Before morning sleep in shift-workers. 
    • Close to local bedtime in travelers. 
    • 2 hours before bedtime in insomnia.6,7,9 
  • Guidelines suggest melatonin: (1) may be effective for jet lag9,10 and delayed sleep phase disorder;11 (2) has insufficient evidence for recommendations in insomnia;8 (3) recommendations in shift-workers variable.9-11  
  • Benzodiazepines, non-benzodiazpines, and antidepressants reduce sleep onset latency by 10-20, 13-17, and 7-12 minutes, respectively.12 
  • Melatonin costs ~$2.00-$7.50/month. 


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Author(s)
Auteur(s)
  • Adrienne J Lindblad BSP ACPR PharmD
  • G. Michael Allan MD CCFP

1. Ferracioli-Oda E, Qawasmi A, Bloch MH. PLoS One. 2013 May 17; 8(5):e63773.

2. van Geijlswijk IM, Korzilius HP, Smits MG. Sleep. 2010 Dec; 33(12):1605-14.

3. Buscemi N, Vandermeer B, Hooton N, et al. J Gen Intern Med. 2005 Dec; 20(12):1151-8.

4. Buscemi N, Vandermeer B, Hooton N, et al. BMJ. 2006 Feb 18; 332(7538):385-93. Epub 2006 Feb 10.

5. Brzezinski A, Vangel MG, Wurtman RJ, et al. Sleep Med Rev. 2005 Feb; 9(1):41-50.

6. Herxheimer A, Petrie KJ. Cochrane Database Syst Rev. 2002;(2):CD001520.

7. Buscemi N, Vandermeer B, Pandya R, et al. Evid Rep Technol Assess (Summ). 2004 Nov; (108):1-7.

8. Towards Optimized Practice. Adult Insomnia: Diagnosis to management. Available at: http://www.topalbertadoctors.org/download/439/insomnia_management_guideline.pdf. Accessed July 3, 2014.

9. Sack RL, Auckley D, Auger RR, et al. Sleep. 2007 Nov; 30(11):1460-83.

10. Towards Optimized Practice. Adult Insomnia: assessment to diagnosis. Available at: http://www.topalbertadoctors.org/download/440/insomnia_assessment_guideline.pdf. Accessed July 3, 2014.

11. Sack RL, Auckley D, Auger RR, et al. Sleep. 2007 Nov; 30(11):1484-501.

12. Buscemi N, Vandermeer B, Friesen C, et al. J Gen Intern Med. 2007; 22:1335-50.

Authors have no conflicts to disclose.