Comparative Study to Determine the Optimal Melatonin Dosage form for the Alleviation of Jet Lag

Abstract

To compare the impact of various dosage forms of melatonin and placebo on jet lag symptoms, 320 volunteers who had flights over 6 to 8 time zones were recruited for a double-blind, randomized, placebo-controlled study. The volunteers received either melatonin 0.5-mg fast-release (FR) formulation, melatonin 5-mg FR formulation, melatonin 2-mg controlled-release (CR) formulation, or placebo. The study medication was taken once daily at bedtime during 4 days after an eastward flight. The volunteers completed the Profile of Mood States (POMS), sleep log, and symptoms questionnaires once daily and the Karolinska Sleepiness Scale (KSS) three times daily prior to departure and during the 4 days of medication intake postflight. A total of 234 (73.1%) participants were compliant and completed the study. The FR melatonin formulations were more effective than the slow-release formulation. The 5-mg FR formulation significantly improved the self-rated sleep quality (p < .05), shortened sleep latency (p < .05), and reduced fatigue and daytime sleepiness (p < .05) after intercontinental flight. The lower physiological dose of 0.5 mg was almost as effective as the pharmacological dose of 5.0 mg. Only the hypnotic properties of melatonin, sleep quality and sleep latency, were significantly greater with the 5.0-mg dose.

Circadian Rhythm Abnormalities

“…However, when the time in the destination is expected to be brief (2 days or less), circadian adaptation may be counterproductive and treatment should be aimed at improving or alleviating jet-lag symptoms. 34 Nonpharmacologic treatment approaches are important in the management of jet-lag disorder. Strategic exposure and avoidance of exposure to light have been utilized as an effective treatment approach.…”

Circadian rhythm sleep disorders

“…Estimations of core body temperature minimum are based upon known relationships with respect to habitual wake time, prompting one to estimate core body temperature minimum timing either 2 or 3 hours prior to sleep offset, depending upon whether one typically sleeps up to 7 hours or more than 7 hours, respectively. [24][25][26] Travel to the west generally favors phase delays, which can be achieved in approximately 2-hour increments (reflecting the greater ease of delaying the clock), by following similar principles. In the opposite pattern, subjects expose themselves to light for approximately 3 hours prior to the core body temperature minimum and avoid light for approximately three hours thereafter (see Figure 3 as an example).…”

“…24,25 Immediate-release preparations appear to perform better than controlled-release formulations. 26 Although most studies have examined the efficacy of melatonin for jet lag occurring subsequent to eastward travel, [26][27][28][29] a single study examined its use in travel to the west and found it to be efficacious. 25 Melatonin use has been studied using a variety of different dosing schedules.…”

“…While benzodiazepine receptor agonists significantly improve subjective and objective night-time sleep parameters, their impact on daytime symptoms of jet lag is unclear. 26,27,[31][32][33] In one head-to-head comparison, the benzodiazepine receptor agonist, zopiclone (5 mg), and melatonin (2 mg) were equipotent. 27 In another study that compared melatonin (5 mg) with a similar medication (zolpidem, 10 mg) and a combination group (zolpidem + melatonin), zolpidem exhibited superior outcomes, and no benefit was conferred by use of these substances in combination.…”

“…Adverse events were nevertheless recorded more frequently in the zolpidem group. 26 Clinicians will need to balance the risk of adverse events with the degree of impairment perceived by the patient in order to help them choose an appropriate agent.…”