Dealing With Jet Lag

Travel to foreign countries is fun and filled with new experiences and adventure. We see different cities, experience different cultures, and meet new people. However, many travelers also experience the frustration from poor sleep and daytime fatigue associated with a trip across several time zones.

Many of our patients also experience disturbing and persistent symptoms of jet lag when traveling to other countries across multiple time zones. If the trip is for a vacation, these symptoms are annoying and irritating. However, individuals who travel for business or professional reasons must be able to function on the first day of arrival, engaging in business negotiations or giving professional scientific presentations. The symptoms of jet lag are very serious and can interfere with their performance. Commercial airline pilots and airline flight attendants may suffer seriously from these symptoms that also may interfere with their job performance. Many patients ask us as sleep specialists about the optimal therapy for decreasing and treating the symptoms associated with jet lag.

Jet lag is recognized in the International Classification of Sleep Disorders: Diagnostic and Coding Manual (Rochester, MN; American Academy of Sleep Medicine, 2006) as an actual sleep disorder. Several recent review articles describe current research and best treatments (Sack. N Engl J Med. 2010;362[5]:440; Auger and Morgenthaler. Travel Med Infect Dis. 2009; 7[2]:60). In his review article, Dr Sack, from the Oregon Health and Science University, has reviewed the current state of knowledge regarding jet lag, including its mechanisms and potential treatment strategies. The symptoms destination country, as well as daytime sleepiness and fatigue. Symptoms can also include a depressed or dysphoric mood and, occasionally, significant cognitive impairment, including memory loss, for example, about events at a business meeting in the destination country.

The pathophysiology of jet lag involves a misalignment between the brain’s internal circadian clock and the local time. The internal circadian clock, located in the suprachiasmatic nucleus in the brain, receives input primarily in the form of light signals from the retina via the optic nerve. This influences the timing of many physiologic functions, such as hormone release. Jet lag symptoms may be frequent and severe in individuals who fly frequently across time zones, such as airline personnel or international business travelers.

Various factors contribute to the severity of jet lag. The more time zones that are crossed, the more severe the circadian desynchronization will be. Traveling in a north-south direction will not result in the same sleep disorder and sense of fatigue as an east-west flight of the same duration. In addition, flying east seems to result in more severe symptoms than flying the same distance in a west direction. The reason for this directional difference is that the actual circadian “day” is slightly longer than 24 hours, and it is easier to “lengthen” our day by flying west than it is to “shorten” our day when we fly east.

Treatment strategies for jet lag have been suggested and include the following: (1) an attempt to realign the circadian clock with the use of exposure to bright light; (2) the use of melatonin planning the optimal timing of the sleep period; and (3) the use of medications to counteract the symptoms of insomnia or daytime sleepiness (see below).

Sleep Strategies To Attenuate Symptoms of Jet Lag

Prior to travel
•Begin to reset the internal clock by advancing or delaying sleep time by 1-2 h.
If traveling eastward, advance sleep time by 2 h, and seek sunlight exposure in the early morning.
If traveling westward, delay sleep time by 2 h, and seek exposure to sun or bright light in the evening.
•If considering the use of a sedative-hypnotic during the flight, take a test dose several days before to judge the drug’s effects.

During flight
•Avoid caffeine in order to assist sleeping on the flight.
•Consider use of a short half-life sedative hypnotic, such as zaleplon, 5-10 mg, or zolpidem, 5-10 mg, during the flight to assist sleep. Avoid longer half-life drugs, and avoid traditional benzodiazepines because of concerns of subsequent amnesia or sleepiness.
•Avoid alcohol on the flight if using a sedative hypnotic.
•Move and stretch legs frequently; walk when possible to avoid DVT.

After arrival at destination
•In the case of eastward travel, seek sun or bright light in the morning hours; stay outside as much as possible to enhance adaptation.
•In the case of westward travel, seek sun or bright light in the evening hours in order to delay the major sleep period.
•Nap during the daytime, if necessary, for travel-related sleep deprivation, but try to restrict naps to 30 min or less.
•Drink coffee during daytime hours to maintain wakefulness during the daytime, but avoid caffeine in the late afternoon or evening to avoid interfering with sleep at night.
•Consider the use of short-acting hypnotic medications for the first several nights until adaptation to the new time zone has occurred.
•In the case of eastward travel, use melatonin, 3 mg, at bedtime in the new time zone to enhance adaptation. In the case of westward travel, use a low dose of melatonin, 0.5 mg, in the second half of the sleep period of the local time zone to enhance adaptation.

The first method of reducing jet lag, according to Dr. Sack, is optimizing light exposure. Exposure to light is the most important external cue for setting the circadian rhythm.

The traveler flying in an eastward direction will have difficulty falling asleep at the usual sleep time in the destination city and then will have a difficult time getting up in the morning, feeling fatigued during the morning hours.

In contrast, the westward traveler will feel sleepy too early in the evening in the destination city and then will wake up too early in the morning, having trouble sleeping throughout the night, which also leads to daytime fatigue and sleepiness.

Exposure to light in the late afternoon or evening shifts the clock to a later time, and exposure to light in the morning has the opposite effect, shifting the internal clock to an earlier time. Exposure to bright light after arrival at the destination city can play an important role in determining the time it takes to resynchronize the circadian clock. The traveler, by seeking out bright light during the daytime hours in the destination city, may be able to accelerate resynchronization of the circadian clock. Therefore, seeking exposure to bright light in the morning after traveling east and in the evening after traveling west is recommended to reduce duration of jet lag.

Melatonin, a natural hormone that is secreted from the pineal gland in response to the light-dark cycle, can also be used to adjust to jet lag. Melatonin is normally released in the evening at the beginning of sleep and, therefore, in one sense, can be considered a darkness signal. Melatonin receptors are present on the suprachiasmatic nucleus. If melatonin is taken early in the evening, before its natural release, it can help to reset the internal circadian clock to an earlier time. In contrast, if melatonin is used in the morning, it resets the clock to a later time, again by imitating a darkness signal. Melatonin itself has minimal hypnotic activity, and most of its effects are related to its effect on the circadian rhythm.

Melatonin is marketed primarily as a nutritional supplement as a 3-mg tablet. Melatonin is generally well-tolerated without significant side effects. Ramelteon is also a melatonin receptor-agonist with a longer half-life and greater affinity for the melatonin receptors than melatonin, and it should be useful in the treatment of jet lag. However, there are few data on its use for this condition.

Hypnotics have also been used to attenuate the symptoms of jet lag. Hypnotics can be taken on the eastward flight to enhance sleep during the flight. Sleeping on the flight may enhance adaptation to the new time zone by reducing sleepiness caused by insufficient sleep on the flight. This sleepiness would promote sleep on the day of arrival at the destination, which would impair adaptation to the new time zone.

Many eastward flights, for example, to Europe, leave in the late afternoon or early evening and arrive in the morning. It is best to avoid sleeping during the day of arrival in order to enhance circadian synchronization with the new time zone. Furthermore, when evening arrives at the new destination, the internal circadian clock may be “set” 6 to 8 hours earlier in accord with the original time zone, making sleep difficult the first several nights. This makes the use of hypnotics a potentially attractive solution to promote sleep in the new time zone.

A randomized controlled study demonstrated that zolpidem, 10 mg, attenuates the sleep disturbance symptoms of jet lag (Jamieson et al. Sleep Med. 2001;2[5]:423). Another study found that a benzodiazepine hypnotic could facilitate adaptation to an 8-hour westward time shift (Buxton et al. Sleep. 2000;23[7]:915).

However, the physician and the patient should take into account potential adverse reactions of sedative hypnotics, as well. Amnesia and confusion are possible side effects of these drugs, especially with the traditional benzodiazepines. A case of especially severe transient global amnesia secondary to triazolam has been reported (Morris and Estes. JAMA. 1987;258[7]:945).

The newer nonbenzodiazepine hypnotics (zolpidem, zaleplon, eszopiclone) are probably safer in this regard, but complex sleep-related behaviors have been reported with these drugs. It is prudent to ask patients for whom these drugs are prescribed to take them at home in order to test their potential side effects.

Drugs that promote wakefulness could be anticipated to improve the daytime fatigue and sleepiness associated with jet lag. Caffeine is commonly used as a safe and easily available stimulant. Modafinil, and its Risomer, armodafinil, could be safe and well-tolerated options to relieve sleepiness. While these drugs are approved for the treatment of narcolepsy, there are few data showing their efficacy and safety in treating jet lag sleep symptoms. One study found armodafinil to reduce sleepiness and improve alertness in patients with chronic shift work disorder (Czeisler et al. MayoClin Proc. 2009;84[11]:958).

These may be attractive options for the business professional or commercial pilot suffering daytime symptoms of jet lag, but there is currently little evidence for their use.

Dr. James Parish, FCCP
Mayo Clinic Arizona
Scottsdale, AZ
Section Editor, Sleep Strategies