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In France there has become available a non-amphetamine vigilance-enhancing drug, without hypertensive effects or, apparently adverse effects on sleep: modafinil (Modiodal). In normal subjects, it increases MSLT (see Glossary) and idiopathic hypersomnia(see Glossary).
The authors used 6 male patients with obstroctive sleep apnea/hyopnea syndrome, ages 49-69, who had an average Apnea/Hypopnea Index (see Glossary) of 38. They all reported excessive daytime sleepiness as represented by more than one sleep attack a day in their sleep diaries.
The design of their study was that of a randomized, placebo-controlled, double-blind, crossover: meaning that all patients received either modafinil or placebo for one two-week period, then the alternative treatment for the second two-week period, without knowing which treatment (modafinil or placebo) they were receiving during a given two-week period.
A 24-hour sleep polysomnogram was done at the end of each treatment period. Also measured at these points were weight, blood pressure, electrocardiogram, and verbal memory. The patients kept diaries of daytime sleep attacks, yawning, daytime alert awake, sleep duration, and quality of sleep for the entire study period.
Only one subject had a blood pressure increase, from 140 on placebo to 170 on modafinil. Modafinil did not appear to affect the electrocardiogram or cause heart arrhythmias. Nighttime PSGs showed no difference between modafinil and placebo, but daytime PSGs showed a 42% reduction in daytime sleep, from 77 minutes on placebo to 45 minutes on modafinil, and sleep diaries indicated about an hour of increased alert waking during the day on modafinil. Modafinil improved memory significantly.
The authors concluded that modafinil may have a role to play in the treatment of obstructive sleep apnea, at least as a complementary treatment to CPAP where excessive somnolence persists. However, it had no effect on the apneas and hypopneas themselves. Its efficacy over the long-term remains to be established.

As discussed in a previous article, a certain small proportion of well-treated sleep apneics remain overly drowsy during the day despite good adherence to their treatment. Sometimes these patients receive stimulants to improve their daytime alertness. However, there are several problems with amphetamine-like stimulants (Ritalin, Dexedrine, Desoxyn, Cylert). One is that they can disturb sleep. Another is that people often become tolerant to them and require increasing doses, possibly leading to physical "addiction" with a "crash-like" withdrawal syndrome when the drugs are stopped. Yet another is that these drugs can raise blood pressure, often already a problem in sleep apneics. Finally, they can be viewed as wholly "symptomatic" treatment, like treating a headache with aspirin rather than discovering the cause of the headache (e.g., migraine, hypertensive) and treating that more directly. However, if the patient is receiving optimal treatment with CPAP and has been shown not to have periodic leg movements of sleep or other directly remediable factors (like side-effects of medications) as a cause of persistent daytime drowiness, some symptomatic treatment for excessive daytime sleepiness and associated impairment of attention and memory may be in order.
What disturbed me most about this study is that, without stating whether the patients were receiving CPAP or not, it leaves one having to assume that they were not on CPAP. It may be difficult to find sufficient numbers of obstructive sleep apneics who remain excessively drowsy on CPAP, but it is exactly this group where a drug like modafinil might come into play.
Also, the brief duration of the modafinil trial leaves unclear whether the patients would develop tolerance to its therapeutic effects with prolonged usage.
Nevertheless, we should acknowledge that some treatment-resistant sleep apnea patients--as well as narcoleptics and those with idiopathic hypersomnia (both of which may coexist with sleep apnea) do receive stimulants, and when modafinil becomes available in this country, it may well take the place of conventional amphetamine-like stimulants as the treatment of choice for these unfortunate people (myself included!). Meanwhile, bear in mind that new drugs often become available in Canada before they get approved for use in the U.S., and it is not unknown for patients to travel to Canada to see a doctor who might prescribe such drugs in such a way that frequent return trips to Canada for follow-up are unnecessary.

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