Staying Up
Humans love to experiment – on ourselves. If a drug works in one arena, it will be tried in another and another. Provigil, (generic – modafinil) is the newest prescription stimulant, even though a version was devised in France in the 1970’s. Okayed by the US FDA for narcolepsy, sleepiness in sleep apnea, shift work cycle disorder, and in some cases for extreme daytime sleepiness, provigil has been studied for official FDA indications on ADD, jet lag, and depression among others, all the latter without success. Yet it’s most common future use may well be in a different category:
None of the above.
Here’s some reasons why:
- Nobody is sure how it works. Provigil clearly jacks up norepinephrine and dopamine, as do standard stimulants like ritalin (methylphenidate) and adderall-speed (amphetamine.) Yet these actions appear to occur lower down in the brainstem than with older drugs.
And provigil promotes histamine effects in the brainstem. Most folks know about anti-histamines like benadryl (diphenhydramine) and use them commonly for allergy (acceptable) or as sleeping pills (less acceptable.) Most don’t know that far more brain neurotransmitters are stimulatory than inhibitory – histamine and hypocretin-orexin (what sadly disappears in narcolepsy) being in that large group.
So it appears that sleep involves turning off stimulating chemicals as much as it does turning on rest-inducing ones. Much of your brain appears built to be used in the “on” position – which may help explain our society based assault on sleep and rest.
- Lots of people are tired and exhausted much of the time, and a quarter of the population does shift work.
Having knocked off 90 minutes of sleep in the last 40 years, Americans are creating a sleep debt similar in size to our Federal budget deficit. Now much of the population, which routinely used to sleep eight hours or more, is skirting along at around 6 hours of sleep, a behavior whose concomitant increases in weight, heart disease, and depression, not to mention brain fog, menace the public health.
And remember that the brain generally likes stimulants. Think of coffee, tea, and energy drinks. So if pharmaceutical companies find a drug that really keeps people awake, lots of people will use it.
That seems to be the case with provigil.
Who Uses Provigil
As a clinician, I’ve been surprised to find many “fatigued” patients coming to me alreading taking the drug. It costs around 15 bucks a pill, has a high DEA ring fence around it as a potentially abusable substance, and possesses clear cut indications from the FDA that insurance companies are very fond of enforcing – after all, the stuff is really expensive. Yet many patients whose sleep disorders have never been fully diagnosed, or diagnosed at all, walk in on the drug.
Many times I try to treat the underlying sleep disorders, which frequently causes the need for provigil to go away. But doctors and medical workers are quite sympathetic with daytime sleepiness and fatigue. The result is many a depressed or chronically insomniac patient is given provigil – until health insurance preauthorization comes into the picture (see the Blog Archive note of December 21st ).
So who else is benefiting from provigil, which many clinicians suspect has far less abuse potential than amphetamine? The answer is people with chronic inflammatory conditions. There are trials showing real advantages to the drug in people with fibromyalgia; chronic fatigue; Parkinsonism; and other rheumatic conditions. But is it usually better than caffeine?
The Secret Uses of Provigil
Militaries around the world found themselves eager to assess if provigil would work in simulated combat situations. The published results are a small fraction of what was actually tried, and came out equivocal. Some studies seemed to show nausea inducing doses were required to produce a useful effect; one researcher of my acquaintance who did multiple long term studies thought sustained release caffeine every bit as good – and a lot safer.
Yet what is clear is that stimulant use has increased in a 24-7 military. Commando raids often are attempted in biological clock dead zones like 4 AM. Provigil can keep people up through the night especially when they need to be continuously vigilant. So can caffeine gum and the traditional stimulant drugs. Who uses what when is something most militaries will not want to discuss.
Militaries know their people’s lives are on the line. It’s the other folks I worry about more.
The Financial Industry, Globe Trotters, and College Students
People under their breath tell me they often take provigil in order to work. They take to perform global trading, trying to stock pick the Hong Kong Market at 2 AM; for office conferences with colleagues in Europe; to cajole their clients in East or South Asia. Others use provigil to overcome jet lag, though Cephalon, the manufacturer, has given up getting an FDA indication after two attempts.
Students use provigil for doing “all nighters.” Some medics use it to work all night.
What are the overall effects of this? When you’re using a drug in a way that’s not perfectly legal, very few will tell. Provigil manufacturer Cephalon may know quite a lot about these “off label” uses, but it’s not in their interest to let others know.
Yet with the advance of pharmaceuticals and a Net based global economy that prefers treating human workers like machines, stimulant drugs will be used more and more. Teenagers now use energy drinks the way young ones eat candy, and new drugs will eventually come down the pike that will more potently keep you up – and up.
What will be the long term effects to the normal regeneration that keeps us healthy? We see it already in sleep deprived populations of teenagers, who text through the night and slumber through the first half of classes, remembering and learning less and less. We see it in their exhausted parents trying to work two or three jobs to make ends meet. We see it in young mothers trying to go to their jobs while relentlessly cutting rest from their “time allotments” until they no longer can stand up to look in the mirror.
Most of the stimulants they use still involve one or another versions of caffeine. What needs to be done is to study what other stimulants, like provigil, will do to “non-medical” populations who adopt its frequent stimulant use – and don’t talk about it to clinicians.
This is one of those cases where it’s better to know than not to know.
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