Provigil and Other Off-Label Medications Used To Treat MS

Patient Expert

I was asked to comment on Modafinil (Provigil ®). It was originally approved by the Food and Drug Administration (FDA) in 1998 for the treatment of excessive daytime sleepiness associated with narcolepsy, and since then has gained FDA-approval for the treatment of excessive sleepiness associated with Obstructive Sleep Apnea, Hypoventilation Syndrome, and Shift Worker Sleep Disorder.

Notice what is missing: MS Related Fatigue. Although there have been studies demonstrating that it is safe and effective in MS Fatigue, this is considered an off-label use of the medication. We doctors use a lot of medications off-label and we are allowed to do so, but it also means that without FDA-Approval, many insurance companies (including Medicaid) will not pay for the medication.

When I traveled to Washington DC last month, I met with a non-profit group called Medicare Rights Center, which has as one of its goals to bring the "consumer voice to the national debate on Medicare reform." One of the big problems is that people with Medicare Part D (which pays for prescription medications until a certain point, called the "doughnut hole' and then picks up again after many thousands of dollars are spent by the person with Medicare) are denied medications that are off-label, even though there is often very good scientific evidence to support the use of these medications, and they are often a last resort.

The basic argument is that Medicare should not be regulating on or off label use of medications (that is an FDA determination), but is supposed to pay for medications written by a doctor because of medical necessity.

So why should you care if you do not have Medicare? Because most insurers follow Medicare's decisions.

So what can be done about MS Fatigue?

The first issue that needs addressing is the source of the fatigue. Most people with MS have fatigue because of poor (and non-restorative) sleep - and this is caused by the same reasons in the general population: poor sleep hygiene (for example, eating in bed), obstructive sleep apnea and even a snoring bed-partner. People with MS may have fatigue that is more than just a sleeping problem, and sometimes it is very difficult for loved ones to understand. MS related fatigue can be quite disabling and is much worse than simple "tiredness."

There are non-pharmacologic ways of treating this, such as biofeedback, meditation, lifestyle modification and acupuncture. There are also medications which have been used: Amantidine, Vitamin B12, Provigil ®, and stimulants (medications like Ritalin ® and Cylert ®).

We applied for and received a University of Florida Deans Grant to study a Complementary and Alternative Medication (CAM) from the Ayurvedic tradition, called Ashwagandha. After we get FDA approval to study this herb (it is considered a food substance and so you could take it now, but we are studying it to see if it really works and is safe, so we need FDA permission, called an Investigational New Drug - IND - application). The trial will study people with MS Related Fatigue and half will receive the real Ashwagandha, while the other half will receive placebo (fake medicine).

Then at a certain point, there will be a cross-over and the group who received the real medicine will now get the placebo and vice versa. This will help us figure out if the medication is really working, or if there is a placebo-effect (where the medicine is only working because everyone gets a little better when thy think they are getting a really good medicine because the mind is very powerful at making us feel a little better, even without any real medicine).