Narcolepsy Treatment May Lead to Abuse




Narcolepsy is a neurological disorder typified by excessive daytime sleepiness. The symptoms of the disorder can be disabling, and for years treatment relied on amphetamines and related stimulants to help patients stay awake. For nearly 2 decades now, modafinil (Provigil) has been available to treat the symptoms of narcolepsy; modafinil has been the preferred wake-promoting drug due to its mechanism of action and safety profile that is distinct from traditional stimulants. It was long believed that modafinil could produce the benefits of the stimulants without the dangerous and unwanted side effects. However, a new study conducted by the National Institutes of Health (NIH), reported in the Journal of the American Medical Association, has shown that it might not be as different from traditional stimulants as once believed.

The National Institute on Drug Abuse, part of the NIH, studied the effects of therapeutic doses of modafinil on the dopamine levels in the brain. Dopamine is a neurotransmitter that influences reward pathways in the brain and mediates euphoria, pleasure, and addiction. Cocaine and amphetamines dramatically increase dopamine levels in the brain, and it was largely believed that modafinil did not have the same effect on dopamine levels. However, the new study reports that modafinil does, in fact, increase dopamine levels in regions of the brain that are critical to the rewarding effects of drug abuse. The researchers concluded that dopamine does play a role in the mechanism of modafinil, and that its abuse potential could be higher than initially considered.

The abuse potential of modafinil might not be worrisome if its use was restricted to patients with significant or debilitating symptoms associated with excessive daytime sleepiness. But, modafinil’s off-label use has increased dramatically in the last few years, and is frequently used for psychiatric indications, including treatment-resistant depression, attention-deficit/hyperactivity disorder, schizophrenia, and cognitive dysfunction. It is also quickly becoming a lifestyle drug for people with various undefined fatigue syndromes, as well as college students, truck drivers, workaholics, and others wanting to find a substitute for sleep. Currently, the United States Food and Drug Administration approves the use of modafinil for shift work sleep disorder and obstructive sleep apnea/hypopnea syndrome, in addition to the excessive daytime sleepiness associated with narcolepsy.

Modafinil has always been viewed as an innocent alternative to traditional stimulants and amphetamines. It was believed to boost the performance of the central nervous system without the cardiovascular side effects and euphoria associated with amphetamines. (The most common side effects of modafinil are mild headache and nausea, and are only reported by about 1% of people who use the drug.) Now it is clear that the more silent effects involving dopamine may have significant consequences. Modafinil’s effects on the brain are similar to other stimulants and drugs of abuse and this may lead to abuse of modafinil in otherwise healthy individuals.

The NIH study was notably small in size, evaluating only 10 healthy male adults, but it highlights the need for further investigation of the true mechanism of modafinil. The potential for abuse and risk of undiagnosed causes of fatigue and sleepiness increase as the off-label use of modafinil grows.

References

Didato, G., & Nobili, L. (2009). Treatment of narcolepsy Expert Review of Neurotherapeutics, 9 (6), 897-910 DOI: 10.1586/ern.09.29

Minzenberg, M., & Carter, C. (2007). Modafinil: A Review of Neurochemical Actions and Effects on Cognition Neuropsychopharmacology, 33 (7), 1477-1502 DOI: 10.1038/sj.npp.1301534

Teitelman E. Off-label uses of modafinil. Am J Psychiatry. Aug 2001;158(8):1341.

Volkow, N., Fowler, J., Logan, J., Alexoff, D., Zhu, W., Telang, F., Wang, G., Jayne, M., Hooker, J., Wong, C., Hubbard, B., Carter, P., Warner, D., King, P., Shea, C., Xu, Y., Muench, L., & Apelskog-Torres, K. (2009). Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain: Clinical Implications JAMA: The Journal of the American Medical Association, 301 (11), 1148-1154 DOI: 10.1001/jama.2009.351

Winder-Rhodes, S., Chamberlain, S., Idris, M., Robbins, T., Sahakian, B., & Muller, U. (2009). Effects of modafinil and prazosin on cognitive and physiological functions in healthy volunteers Journal of Psychopharmacology DOI: 10.1177/0269881109105899

  • windhill

    Having taken both Provogil and amphetamines to treat MS-related fatigue I can attest to their similar effects. Provigil is a little gentler on heart rate and seems to leave me less cranky, otherwise the effects are very similar. On “bad”days all it seems to do is wake me up enough to let me know how tired I am….

    One factor likely to lessen abuse is the outrageous price of $10/day. No generic is available in this country and the insurance companies only approve it for specific diagnoses, and will not let you exceed your monthly allowance if you are lucky enough to be covered. ( I am not) I wouldn’t know if it is available on the street. .

  • Bruce

    Provigil first reached the US market in 1998. For reasons which defy logic no serious attention was paid by the FDA to nine years of reports by ER doctors and cardiologists of known deaths caused by Provigil and its twin Nuvigil , which by late 2007 had already numbered into the the 1000s ( THOUSANDS ) according to the FDA’s own records. Finally, in 2006 an FDA committee refused to permit Provigil ‘s manufacturer, Cephalon, to market Provigil ( under the name Sparlon ) for the treatment of ADHD because, while Provigil was effective for ADHD, the physicians determined that Provigil was simply too dangerous for such widespread use.

    With the grave dangers Provigil presented finally disclosed in that 2006 decision, a year later the FDA issued warnings to the the medical community and ordered Cephalon to include bold-print warnings of Provigil ‘s potential for causing various manifestations of what has been called ” Delayed Reaction Drug Hypersensitivity Syndrome”. This syndrome, not to be confused with the everyday allergic reactions which most drugs are capable of causing , is an insidious one because it does not occur soon after Provigil therapy is begun but rather occurs no sooner than 2 weeks after daily use has started and usually no later than 3 months after.

    The illnesses Provigil causes once they manifest themselves are invariable sudden, severe , at first inexplicable , and life-threatening if the condition is not recognized promptly . These conditions include Stevens – Johnson syndrome . TENS and other sudden severe manifestations of skin rashes whcih can, within 24 hours, become functionally identical to 3rd degree burns and as disfiguring. Less easily identified and thus far more likely to remain unattributed to Provigil , even post – mortem. is DRESS syndrome, a condition which, once it takes hold can lead to a near total shutdown of the body’s vital systems – the kidneys, the heart, the lungs the liver the intestinal system and the brain. Only heroic and immediate medical aatention in the form of total life support can forstall a rapid death. At that survival is no more than 20% after 48 hours.

    I was struck down by DRESS syndrome 2 months after I began taking Provigil. While I did defy the odds in surviving the complete breakdown of my bodily systems, my survival such as it is was not one involving what I would call “luck” , other than it gives me the opportunity to warn others of this so-called ‘innocuous’ drug and to suggest that those who need to remain awake rely upon upon dextroamphetamine, a remarkably safe drug with a 75 year track record of safety.

  • Lesley

    Interesting, Bruce.

    I researched provigil very well when I first went on it and found very little of this information. Can you post sources? ‘m not denying that you went through something horrific with DRESS. For me, provigil has been a lifesaver and I’m not eager to stop taking it, but if it’s too risky, I will weigh the evidence. But I need to find evidence.

    I know about Stevens-Johnson syndrome and Sparlon. I’m talking about the number of cardiovascular events and whether the thousands of deaths are more than you’d expect with any other drug of this class?

    Anyway, if you point me in the right direction, I’ll look it up. Thanks for the heads-up.

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  • LBickers

    I was diagnosed with Narcolepsy in 1998. I took Provigil the first time in 2000. I went off of it when I became pregnant and started back on Provigil in 2007 when my symptoms could no longer be controlled without the medication. Since starting back on my current dose of 300 mg a day ( I do not utilize the entire dose unless I will be driving long distances) of which I take 200 mg on a regular basis, other than the initial “getting used to” the drug, I have not experienced any ill side effects and am able to go without the drug on the weekends and when I am not going to be engaging in activities that might otherwise bring on more fatigue. I also would like to say that although I take 200 mg a day, my blood pressure remains a steady 90/60 and a heart rate of about 80. I would not be able to lead a “normal” life without Provigil and would like to state that all drugs have different effects on different individuals. I had to change my lifestyle to accommodate my illness and the Provigil helps me to function on a daily basis. I am thankful for this drug. My only complaint is that Cephalon will not lift its hold on the drug to allow a more affordable generic form of this medication. I would not be able to take it if not for my coinsurance. This drug is ridiculously priced at $900 for 90 pills and $550+ for 60 pills. I feel for those individuals with this illness that do not have the means to purchase this if they suffer from narcolepsy.

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Jennifer Gibson, PharmD

Jennifer Gibson, PharmD, is a practicing clinical pharmacist and medical writer/editor with experience in researching and preparing scientific publications, developing public relations materials, creating educational resources and presentations, and editing technical manuscripts. She is the owner of Excalibur Scientific, LLC.
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