Drugs for Jet Lag
With all the stress of travel these days - the requisite shoe-removal, luggage surcharges and now the possibility of body scans - there may soon be relief for one travel headache that's been about as immutable as traffic on the way to the airport. Jet lag. The U.S. pharmaceutical company, Cephalon, is currently awaiting FDA approval for Nuvigil, a drug that promises to combat the sleepiness associated with jet lag.
If it gets the nod, Cephalon will market Nuvigil to business travelers who plan to stay abroad for just a couple of days. That's because Nuvigil is not actually meant to set travelers' internal "circadian" clock to a distant time zone, but rather to keep them awake enough to get through a business meeting when they arrive at their destination. The idea of stay-awake drugs is not new. In fact, Nuvigil is a chemical cousin to Cephalon's hugely successful Provigil, the stimulant drug that college kids cramming for exams and soldiers in the field have been downing for years. Nuvigil works almost precisely the same way as Provigil does and since June has been available to treat disorders like sleep apnea and narcolepsy. But only Nuvigil could be become the first-ever drug approved for jet lag.
Should you take Nuvigil or any stay-awake drug to cope with overseas travel?
Two experts debate the issue: Richard Bogan, MD, the lead investigator for the Nuvigil clinical trial and Leon Kreitzman co-author of Rhythms of Life: The Biological Clocks that Control the Daily Lives of Every Living Thing
Dr. Richard Bogan:
"As a clinician, if a patient comes to me and says 'I'm going to Paris, I feel sleepy when I get over there and need to function well - do you have something for me?' I'd say, yes, if Nuvigil is approved. The science is there for us to prescribe something. There are a number of behavioral strategies to change your circadian clock to combat jet lag, but they take a number of days. Instead, we have a compound that will improve the wakefulness of people who need to function normally when they arrive in a foreign country."
"In our study, the majority of patients who took Nuvigil had significant improvement in their wakefulness measured subjectively or objectivity and the side effects were mostly mild," says Bogan.
Why not just take Provigil, which already available has a proven track-record for keeping people awake? "I suspect that Provigil will work and there is nothing to prevent people from taking Provigil for the sleepiness associated jet lag," says Bogan, "but it's not approved by the FDA for that."
Bogan adds that Nuvigil would work better anyway because it lasts longer. "Nuvigil has a longer half-life than Provigil, meaning it takes longer to wear off and you stay awake longer. The idea is for travelers to keep awake for 15 hours once they arrive at their destination and then sleep for eight hours that night." Says Bogan: "The drug doesn't affect your ability to get to sleep when you want to and stay asleep."
Bogan says that researchers don't know exactly how Nuvigil works. "We know Nuvigil is not an amphetamine. And based on the science it wouldn't prevent you from going to sleep at night when you want to. And from a theoretical perspective, it shouldn't interfere with your body's ability to adjust its circadian clock if you want to adjust."
What about side-effects? "Most people in the study experience no or mild side effects," says Bogan. However, he says, "some patients can't take the drug. They experienced headache, dizziness, nauseous and a very low number experienced vomiting."
"Jet lag and sleepiness after travel are not life-threatening. You might miss a night of sleep or two nights sleep, but this is not a medical, much less life-threatening condition. I suspect that what's underlying the company's push for a new drug is not that they are offering a genuinely therapeutic agent. It's a marketing decision. The patent for its Provigil is coming up in a few years. The drug maker is looking for a variant of Provigil to keep its hold on market share. And in the process, they are using a drug to provide something that's really just about lifestyle."
"There are indeed great things about Nuvigil and Provigil. Typically, they can keep you awake without obvious short-term side-effects. But the truth is we don't know about the long-term side effects of these drugs. The company is marketing Nuvigil for business travelers who go someplace for just a day or two and may need the drug occasionally, but what if these folks take it every time they travel, time and again. The problem is that for ethical reasons nobody can do a long-term study to find out.
"Jet lag is due to a disruption in one's 24 hour circadian rhythm. The rhythm adapts to whatever local condition you're in. If you go to another part of the world, say, a place that's10 hours ahead of you, it'll take one hour per day or 10 days to adjust. But when you first arrive, your body's physiological functions are out of whack. For some, jet lag affects sleep patterns, so they feel fatigued. For others, decision-making may be impaired and others will experience bowel irregularity."
"The problem is that there isn't one circadian clock in the body. There are many rhythmic clocks, each for different functions. The liver may be timed to the schedule of food intake, while the brain takes different cues. Then like an orchestra, there is also a master clock which tries to keep all the different clocks together. But when you go on a long trip, that master synchronization breaks down and instead of getting a nice tune you get cacophony. Nuvigil, as far as we know, does nothing to address the rhythms of our body. It will do nothing to quell the cacophony that results from traveling through time zones. But it will keep you awake without feeling fatigued."
"In my opinion, most people can handle the sleepiness associated with jet lag for one or two days. Even so, you could do things without drugs to make the transition to another time zone easier. There's not much point in trying to completely switch over your circadian rhythm if you're gone for just a couple of days, because you'll be right back home again. Still, trying to shift your body slightly might make you feel better."
"What can you do? Try to prepare your body before you go. You might go to bed a different time a couple days before you travel. Try to moderate the timing of your meals, too, to match your destination meal time. Don't drink alcohol on the plane; it seems to have a reinforcing effect on jet lag. Instead, drink plenty of water. Eat moderately - try to have fresh food because your body has less capability of digesting fatty food at night. And if you're arriving in the morning, then do look at sunlight to tell your body it's morning."
"Actually, the more sensible thing is to go a day earlier and start switching over your clock to local time. Of course, if your internal clock shifts to the new time, that might be harder for you when you come back. You'll probably come home and crash a bit."