Daytime Sleepiness Drugs of Varying Performance in Obstructive Sleep Apnea

One drug stood out for reducing excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) in a meta-analysis, researchers reported.

Compared with placebo, users of solriamfetol (Sunosi) showed improvement on the Epworth Sleepiness Scale (ESS; mean difference -3.8, 95% CI -5.24 to -2.50) after 4 weeks, as did groups taking armodafinil/modafinil (mean difference -2.25, 95% CI -2.85 to -1.64), and pitolisant (Wakix) or other H3-autoreceptor antagonists (mean difference -2.78, 95% CI -4.03 to -1.51), reported Dena Zeraatkar, PhD, of McMaster University in Ontario, Canada, and co-authors.

On the Maintenance of Wakefulness Test (MWT), solriamfetol (standardized mean difference [SMD] 0.90, 95% CI 0.64-1.17) and armodafinil/modafinil (SMD 0.41, 95% CI 0.27- 0.55) showed different magnitudes of improvement over placebo, according to the systemic review and meta-analysis published in the Annals of Internal Medicine.

"We expected to see solriamfetol do well, but not necessarily that much better than modafinil/armodafinil. However, in both main outcomes (MWT and ESS), solriamfetol did perform better," co-author Tyler Pitre, MD, MA, also of McMaster University, told MedPage Today.

The signal of serious adverse events trended strongest for armodafinil or modafinil (RR 1.28, 95% CI 0.44-3.7), translating to 8.4 more events per 1,000. The most common events across the board were anxiety, headaches, and insomnia. Headaches were most likely to occur when taking armodafinil or modafinil, while insomnia was more likely with both armodafinil/modafinil and H3-autoreceptor antagonists.

Despite the efficacy shown by the drugs tested, the researchers noted that adverse events were serious enough to warrant consideration -- noting that when compared with placebo, the stimulant-like drugs armodafinil and modafinil may be associated with an increase in drug discontinuation, as may solriamfetol, albeit with less certainty.

"Solriamfetol, armodafinil-modafinil, and pitolisant reduce daytime sleepiness for patients with OSA already on conventional therapy; solriamfetol is likely superior in effectiveness," the group wrote. "Adverse events probably increase the risk for discontinuation of armodafinil–modafinil and may increase the risk for discontinuation with solriamfetol. Although solriamfetol may have led to more discontinuations from the trials due to adverse events, we did not find convincing evidence of serious adverse events, albeit with very short-term follow-up."

Pitre also noted that the medications analyzed are not meant to be used in the place of traditional OSA treatments, but as additions to assist when daytime sleepiness persists despite treatment.

"Clinically, family physicians, internal medicine and pulmonary medicine specialists all have patients with OSA who are still tired despite adhering to their CPAP [continuous positive airway pressure therapy]. Medications have been available for a long time and with the introduction of solriamfetol, we have more effective means to deal with this issue with patients," he said.

The meta-analysis covered 14 trials with participants having baseline ESS scores of at least 10 and excluding people with sleep disorders other than OSA.

A total of 3,085 participants were included in analysis, which featured an average patient age of 50 years, and a 71% male population. The patient population was 18% Black and 77% white.

Researchers cautioned that the trials analyzed were all performed in high-income countries. They also cited the short follow-up in included trials, as well as a "lack of a core outcome" for OSA patients analyzed.

The authors encouraged further research, particularly into the long-term effects of available medicines. Zeraatkar also noted that recent findings regarding the link between effective CPAP use for OSA and individual chronotype could be areas for further exploration, as well as how these medications may affect patients with varied sleep schedules.

"With regards to recent research concerning chronotypes, to our knowledge, there are no subgroup analyses for these drugs for any specific chronotype. However, we may hypothesize that patients who derive less benefit from CPAP may derive more benefit from these medications to improve their sleepiness scores. It would be interesting to see future research address whether there is an association between these chronotypes and EDS, for example," she told MedPage Today.

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