Jet lag and melatonin

• jet lag syndrome emerged with the rise of long haul air travel - symptoms include disturbed sleep, loss of concentration, increased fatigue, and increased irritability during the new daytime, and yet difficulties in initiating and maintaining sleep at night
  
  
• long flights are also often uncomfortable and tiring (travel fatigue), and the dry cabin air contributes to dehydration
  • travel fatigue can be distinguished from those of jet lag by comparing flights across time zones, for example from Europe to Asia, with flights of similar length along the same meridian, say to southern Africa, which cause travel fatigue but no jet lag (1)
    
    
• jet lag is caused by the desynchronisation between various body rhythms and environmental rhythms
  • symptoms are usually temporary and resolves when the endogenous circadian rhythm resynchronizes with the physical environment
  • severity of the symptoms may vary according to the number of time zones crossed and the direction of travel e.g. - people who take eastward flights have more sleep disturbances than people who travel towards the west (2)
  • the cycle of sleep and activity is the rhythm most noticeably affected, with the associated changes in physical and mental functioning - rhythms are regulated by the interaction between internal and external factors:
  • an example of interaction between internal and external factors:
    • "body clock" which controls secretion of melatonin by the pineal gland, an important internal factor, and light
      • melatonin is synthesized at night under normal environmental conditions
        • the endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained by the light/dark cycle
        • light is able to both suppress or synchronize melatonin production according to the light schedule
        • melatonin can be considered as the output (the hand) of the endogenous clock
        • exogenous melatonin is able to influence the endogenous secretion of the hormone according to a phase response curve
  • with a rapid change of time zone, it takes several days for the external factors to shift the phase of the body clock from the time zone just left to the new zone - if this adaptive shift is speeded up then jet lag can be alleviated or prevented
    

Treatment:

• non-drug measures in management of jet lag
  • these aim to maximise the external environmental cues that push the circadian phase towards the rhythm of light and dark at the destination - these changes may be worth trying to start this before departure
  • the most important cue is light
    • regardless of the course of travel, people should try to stay awake during the daytime at the destination (2)
    • after a westward flight - changes in behaviour would be to stay awake while it is daylight at the destination and to try to sleep when it gets dark
    • after an eastward flight - changes in behaviour would be to be awake but avoid bright light in the morning, and to be outdoors as much as possible in the afternoon
    • these changes in behaviour will lead to an adjustment in the body clock and turn on the body's own melatonin secretion at the right time
  • other cues can reinforce this change in the body clock e.g. eating modestly at the times that correspond to one's usual mealtimes, taking comfortable exercise, and seeing favourite sights at times when bright light is advised (1)
  • it is unclear whether alcohol or caffeine affect adaptation although it seems more likely that they hinder rather than to help adaptation (1)
  • when the stay at the destination is short (i.e., two days or less) travellers may be advised to keep a home-based sleep hours rather than adopting to the destination sleep hours to minimise sleepiness and jet lag symptoms (3)
    
    
• melatonin and drug measures e.g. a short acting hypnotic
  • melatonin taken at bedtime both shifts the phase and has a hypnotic effect
  • a hypnotic treats one symptom by providing sleep - however does not shift the circadian phase
  • a review stated that (4):
    • a licensed form of melatonin is marketed for the short-term treatment of jet lag in adults.
    • evidence of efficacy largely comes from small studies in which the source and form of melatonin were not always reported.
    • meta-analysis of data from four studies (232 participants) showed that jet lag severity (assessed using a 100-point scale) was 27 with melatonin and 45 with placebo.
    • drowsiness and sleepiness, headache, dizziness and disorientation are the most frequently reported adverse effects with melatonin
  • hypnotics (zopiclone or zolpidem), taken before bedtime on the first few nights after flying, may reduce the effects of jet lag by improving sleep quality and duration but not other components of jet lag (5)

The Summary of Product Characteristics (SPC) must be consulted before prescribing any of the drugs mentioned.

Reference

• 1. BMJ 2003 Feb 8;326(7384):296-7
• 2. Barion A, Zee PC. A clinical approach to circardian rhythm sleep disorders. Sleep Med. 2007;8(6):566-577
• 3. Morgenthaler TI et al. Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders - An American Academy of Sleep Medicine Report. Sleep. 2007;30(11):1445-1459
• 4. Drug Ther Bull. 2020 Feb;58(2):21-24
• 5. Herxheimer A. Jet lag. BMJ Clin Evid. 2014 Apr 29;2014