© 2003 American Thoracic Society
Modafinil and SleepinessTo the Editor:I enjoyed the Pro/Con Debate of Drs. Black (1) and Pollak (2) and the associated Essay by Dr. Pack (3). Like Pollak and Pack, I have significant concerns about the widespread use of modafinil. Dr. Black is economical with the truth when considering fears that patients with obstructive sleep apnea (OSA) taking modafinil might lose their incentive to use continuous positive airway pressure (CPAP). He states "All evidence thus far, however, suggests otherwise—CPAP-compliant patients taking modafinil do not reduce CPAP use." This was not the finding in a double-blind study we performed and published in this journal (4). Modafinil decreased CPAP use significantly, albeit by a small amount (3%) in a short-term study. Furthermore, this study was analyzed entirely independently, and there is an urgent need for more independent studies to clarify the conflicting data. Dr. Black (1) also states "It is well established that approximately 30 to 50% of patients with diagnosed OSA are CPAP noncompliant." This figure is highly dependent on patient selection (5) and the support provided to them, and must be seen in the context that noncompliance with all long-term medication is 30 to 50% (6). Given the cardiovascular benefits of CPAP (7), the first-line treatment of CPAP noncompliers must be to try to improve CPAP use; if this fails, provide patients with alternative effective treatment for their apneas. This must supersede any temptation to give them a medication that has no effect on cardiovascular risk and little effect on symptoms; the benefits in terms of Epworth Sleepiness Score range from (a nonsignificant) 2 to 3 for modafinil over placebo in the studies cited by Black (1) in comparison with 3 to 7 for CPAP over placebo in the studies cited by Pack (3). I share Dr. Pack's concerns about the Food and Drug Administration (FDA) considering a broad indication for modafinil use in excessive sleepiness. Subjective sleepiness is frequently a response to inadequate sleep, shift work, or psychological factors. To provide a medication with poorly documented long-term side effects to such individuals is not good medicine. Even if use was limited to patients with "sleep disorders" with continued sleepiness, I share Dr. Pack's concern that this would prejudice accurate diagnosis and specific therapy. Furthermore, some alleged "sleep disorders" such as periodic limb movement disorder, are so prevalent that most of the elderly would still be in line for modafinil treatment. Modafinil is useful in the treatment of narcolepsy. The FDA would be well advised to limit its use to areas where there is a sound evidence base.
Department of Medicine University of Edinburgh Edinburgh, Scotland FOOTNOTES Dr. Charles Pollak and Dr. Allan Pack were given the opportunity to respond to this letter but declined to do so. REFERENCES
From the Author: Dr. Douglas refers to the Pro/Con debate, which ultimately proved to be without great contrast in perspectives (1, 2). Concern exists on both sides that some patients may reduce or eliminate continuous positive airway pressure (CPAP) use in response to improved daytime alertness with modafinil. Treating physicians must monitor CPAP compliance when adding modafinil for residual sleepiness. Prudent management mandates that modafinil prescriptions be discontinued in patients with reduced compliance in response to modafinil treatment, when and if this may occur. Moreover, inadequate management of sleep-related airway obstruction before modafinil initiation is untenable. All appropriate measures must be used to ensure optimal use of and benefit from CPAP or from alternative treatments when CPAP fails. Adequate sleep-related airway management is essential as primary treatment to ameliorate obstructive sleep apnea (OSA)-related cardiovascular risks (3, 4). With CPAP as primary OSA management, treatment optimization frequently requires multiple interventions that can include mask refitting, humidification, and retitration with esophageal pressure monitoring, among many others. In addition, long-term follow up is critical. When patients continue to experience daytime sleepiness despite optimal airway management, compassionate care dictates the pursuit of secondary treatments to temper the residual sleepiness. Well conducted, controlled treatment trials exist suggesting that patients with OSA with residual sleepiness may experience improved alertness with the addition of modafinil to primary treatment (nasal CPAP) without evidence of reductions in CPAP use for up to 12 weeks (5, 6). In many areas of medicine, when primary treatment fails to eliminate condition-associated symptoms, secondary measures are used, if available, to provide further symptom relief. Again, this is the compassionate approach. If, however, secondary treatment of symptoms yields reduced compliance with primary treatment, the ultimate value of the secondary treatment is called into question. I maintain my original claim that modafinil has a role in the treatment of residual sleepiness in patients with OSA, after the institution of proper primary upper airway management of sleep-related obstruction. As is always the case in medicine, judicious prescribing is imperative. In addition, the potential role of modafinil in the treatment of primary OSA-related sleepiness when the patient is unable to adequately tolerate CPAP and other treatments fail, has not been studied, and is entirely a separate matter, but one that may be worthy of further evaluation.
Stanford University Stanford, California REFERENCES
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