On Treatment but Still Sleepy

Cause and Management of Residual Sleepiness in Obstructive Sleep Apnea

Sandrine H. Launois; Renaud Tamisier; Patrick Lévy; Jean-Louis Pépin

Disclosures

Curr Opin Pulm Med. 2013;19(6):601-608. 

In This Article

Management of Residual Sleepiness

The first step in managing residual sleepiness is a thorough diagnostic assessment ruling out all potential causes of sleepiness.

Subjective report of sleepiness does not always correlate well with objective measures.[37] An objective measurement of alertness may be needed to ascertain sleepiness severity. Furthermore, if sleepiness is deemed severe enough to require treatment with an alerting drug, an objective evaluation at baseline will allow proper assessment of vigilance on treatment. Such assessment is particularly useful when an alerting drug is prescribed off-label.

Sleepiness, regardless of its cause, leads to increased reaction time, inattentiveness or micro-sleep episodes, thus diminishing driving ability.[38] As mentioned earlier, residual sleepiness patients have moderate-to-severe sleepiness. Consequently, although no study has specifically examined driving performances in residual sleepiness patients, the risks of driving while sleepy should be discussed with patients.

After exclusion or treatment of all other causes of sleepiness, it may be justified to initiate treatment with a stimulant drug in patients with severe residual sleepiness, particularly in patients who drive. Methylphenidate has not been tested specifically in this indication. Randomized controlled trials testing modafinil or its enantiomer armodafinil to treat residual sleepiness have demonstrated significant improvement in various measures of sleepiness, fatigue and quality of life ( Table 1 ).[31–36] Although most measures show statistically significant improvement on modafinil or armodafinil compared with placebo, the amplitude of the change is small and does not always carry a strong clinical significance. At the conclusion of the trials that have reported these data, a significant proportion of patients were still sleepy in spite of combined CPAP and stimulant treatment.[33,35] In only one of these trials, a statistically significant but clinically negligible decrease in CPAP nightly use of approximately 12 min was recorded.[36]

Most of the studies on the use of modafinil or armodafinil are short-term trials, with at most 12 weeks of treatment; however, tolerance is remarkably satisfactory in these patients who may be at risk for cardiovascular complications, with no serious adverse events reported. Of note, in a large group of middle-aged, obese OSA patients, no significant difference in newly diagnosed hypertension or worsening of preexisting hypertension was observed after 12 weeks of treatment with 150 or 250 mg of armodafinil or placebo.[33]

Indeed, modafinil and armodafinil have been approved in some countries for residual sleepiness treatment. Unfortunately, in November 2010, the European Medicines Agency (EMA) restricted the approval of these medications to the treatment of narcolepsy. The EMA based its decision on methodological grounds (lack of large, randomized studies), on safety issues (lack of pharmacovigilance data for blood pressure) and on the unresolved question, as discussed above, of whether or not residual sleepiness is a specific entity in OSA patients. Clinical trials of residual sleepiness treatment with H3 receptor agonists are currently underway and may provide a useful alternative in countries where modafinil and armodafinil are not approved for the treatment of residual sleepiness.[47]

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