I’m Leaving on a Jet Plane . . .When Will I Be Able to Sleep Again?

Are there any effective remedies for jet lag?

In an effort to make the twain of east and west meet through air travel, we take off to distant sites for either vacation or business. Whether the destination is eastward to Europe or westward to Hawaii, afterward there is one devil to pay: jet lag. It affects our quality time “there” as well as our readjustment after we return. The same can be said for those who work variable shifts or start their work very early in the morning. Melatonin, the natural sleep regulator, has been used with minor success to induce and maintain restful sleep, but melatonin preparations in the United States are an unregulated potpourri of multiple doses and varieties. Two recent trials and an accompanying editorial published online in Lancet seem to be a step in the right direction for shift work or jet lag insomniacs.^1,2

EFFECTS OF A MELATONIN AGONIST ON SLEEP EFFICIENCY

Melatonin regulates sleep (at higher blood levels) and wake (at lower levels) cycles. It is the alarm clock for our daily circadian cycles. Tasimelteon is a melatonin agonist (affecting both known melatonin receptors) that was studied in 2 randomized, double-blind, placebo-controlled trials. The sleep stressor was a 5-hour change in cycle followed by the effort to fall asleep earlier than usual. The fragmented aspects of sleep after disruption caused by shift change or jet lag were studied: time latency to fall sleep, staying asleep, and rapid eye movement (REM) sleep. For the “staying asleep” segment, it has been observed that sleep maintenance in the middle third of a cycle is adversely affected by travel across time zones or shift changes.

Levels of melatonin were measured in participants in both phases of the study. Forty-five persons were enrolled in the phase 2 trial; 412 were enrolled in phase 3. Sleep quality was monitored by polysomnography, in addition to subjective reporting.

In both trials, tasimelteon reduced insomnia resulting from shifts in the sleep-wake cycle. A dose of 20 to 100 mg of the agonist improved latency, polysomnographic recordings, and sleep maintenance, including the potentially disrupted middle third of the cycle. With placebo, sleep efficiency was still disturbed in the middle third of the cycle. In addition, REM sleep was also positively affected by the melatonin agonist. Adverse events were minimal; none were serious.

CAVEATS ABOUT THE STUDY RESULTS

The authors were frank about the study’s potential shortcomings. The phase 2 trial had a small sample size. The study was funded by the pharmaceutical company that will market the drug if it is approved. However, even though the sponsor was involved in study design, the sponsor did not participate in data collection. Also, the authors made the final decision regarding publication. Finally, “daytime effects” after the improved active drug sleep were not evaluated. Will the druginduced corrections in sleep make for an “up and at them” the next day?

Until now, the last refuge for the sleep disturbances of shift change or air travel has been benzodiazepines- obviously not ideal agents in this regard. Although the studies summarized here are to be interpreted as preliminary, it appears that there may be nonaddicting and safe products on the market in the near future to help those who suffer insomnia after travel or as a result of their work schedule.

References:

REFERENCES:1. Rajaratnam SM, Polymeropoulos MH, Fisher DM, et al. Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials [published correction appears in Lancet. 2009;373:1252]. Lancet. 2009;373:482-491. http://www.thelancet.com. Accessed June 23, 2009.

2. Cardinali DP, Golombek DA. Let there be sleep-on time. Lancet. 2009;373: 439-441. http://www.thelancet.com. Accessed June 23, 2009.