© 2003 American Thoracic Society
ConModafinil Has No Role in Management of Sleep ApneaDivision of Sleep Medicine Department of Neurology Ohio State University Columbus, Ohio Modafinil has proven to be an effective and well-tolerated drug for the control of excessive daytime sleepiness (EDS) in narcolepsy (1) and, increasingly, other disorders associated with EDS or fatigue (2). In a recent study, it has been shown to reduce residual EDS in patients with obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP) (3). In another study (4), some but not all multiple objective outcome measures of EDS improved. As a result, the use of modafinil in OSA can be expected to increase. The mechanism giving rise to EDS is quite different, however, in narcolepsy and OSA. In narcolepsy, EDS is a central manifestation of a neurologic disorder. In contrast, there are several reasons for thinking that sleepiness in OSA arises indirectly as a result of functional airway obstruction: (1) apneas and hypopneas are associated with end-apneic arousals that result in fragmentation of sleep (5); (2) experimental fragmentation of sleep is also associated with EDS, even in the absence of sleep loss (6, 7); and (3) alleviation of OSA by CPAP promptly and lastingly diminishes EDS, though objective measures may only improve and not return to normal (8). The distinction between EDS as a primary neurologic symptom and a consequence of fragmented sleep implies that by treating OSA we also remove a cause of EDS. This may be of medical significance, because OSA can lead to cardiovascular disorders (pulmonary hypertension, right heart disease, cardiac arrhythmias, systemic hypertension, and others). Suppressing EDS with modafinil will almost certainly not diminish these complications and may even do harm by obscuring the presence of medically significant OSA and reducing CPAP compliance (4). Because it predictably results from OSA of sufficient severity, EDS is a valuable indicator of sleep-disordered breathing that can help the clinician decide whether to obtain a polysomnogram from a new patient, whether to treat OSA, whether the treatment is effective, and whether it remains effective for years. When a patient presents with EDS, a diagnostic polysomnogram should immediately be ordered, because EDS is the complaint that is most predictive of clinically significant sleep apnea. It would not be appropriate to prescribe modafinil instead. Even EDS that does not seem to be caused by OSA should not be suppressed with medication, because its response to the treatment of OSA is a valuable diagnostic sign that should not be obscured. This does not mean, of course, that modafinil (or alternative drug) should not be prescribed for a short time for a sleepy driver who is judged unlikely to desist from driving until EDS has responded to more specific treatment, such as nasal CPAP. Deciding whether to treat OSA will depend on (1) the presence and severity of EDS and (2) the measured frequency of apneas and hypopneas. Both are important, for a patient that does not experience a treatment-responsive symptom such as EDS is unlikely to accept and comply with CPAP. Suppressing EDS with modafinil would therefore subvert recruiting the patient to definitive therapy. After treating OSA with CPAP for several weeks, the clinician must decide whether to approve the long-term use of CPAP. A major criterion will be the success of CPAP in reducing EDS. The clinician will be concerned with matters such as driving safety, whereas patients may be more concerned with how well they feel, work productivity, ability to sit through TV shows, etc. If modafinil is simultaneously exerting an effect, a rational decision regarding CPAP cannot be made. Even after years of CPAP use, recurrence of EDS may alert us to the possibility that OSA has returned or worsened. The usual reason is mechanical (e.g., leakage requiring mask replacement), but the CPAP pressure requirement may have increased as a result of weight gain. Treatment failure should prompt an investigation, not the pharmacologic suppression of symptoms. Modafinil therefore has no more place in the long-term management of sleep apnea than it does in its initial recognition, diagnosis, and treatment. There are several reasons why a treatment may fail to eliminate OSA and EDS, including inadequacy of the treatment modality (upper airway surgery, intraoral appliance), CPAP-mask leakage, incorrect CPAP pressure, and noncompliance with treatment. If the frequency of apneas cannot be reduced to asymptomatic levels with CPAP, another cause of continued sleep disruption should be sought. There may, for example, be a site of upper airway obstruction in addition to the usual oropharyngeal mechanism (e.g., hypopharynx). Suppressing EDS with modafinil would reduce the likelihood of searching for and finding such a mechanism. It is uncommon for a thorough work-up and well-implemented CPAP to fail to reduce obstructive apneas to asymptomatic levels. If EDS should persist, however, it may be attributed to OSA when it is in fact caused by a neurologic disorder (narcolepsy, myotonic dystrophy), by drug effects, or, most commonly, by insufficient nocturnal sleep. Sleep deprivation occurs in many shiftworkers and also in those who get up very early to begin work. It results from forced early termination of sleep by alarm clocks, combined with relatively late bedtimes, and results in failure to fulfill the nightly need for sleep. Even compensatory weekend sleep does not provide sleep when it is most needed, i.e., on days when people must be alert on the job and on the drive to and from the workplace. A sleep log should reveal whether a patient is failing to average at least 7.0 hours of sleep a day. Modafinil might reduce EDS in such patients, but an extension of sleep hours would be more effective and specific. In summary, we have considered the main stages of managing sleep apnea as well as several reasons why treatment may fail. In none of these situations is it desirable to suppress EDS pharmacologically, and doing so may be harmful. It is therefore an unavoidable conclusion that modafinil has virtually no role in the management of sleep apnea. REFERENCES
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