Comparing Treatments for Excessive Daytime Sleepiness in OSA

Patients with obstructive sleep apnea (OSA) can develop excessive daytime sleepiness (EDS). Pharmacologic agents are used to promote wakefulness in this population; however, according to a study in Annals of Internal Medicine, the effectiveness of these agents has not been directly compared. Lead author Tyler Pitre, MD, MA, and colleagues performed a systematic review and network meta-analysis to compare pharmacologic agents for EDS in OSA.

After analysis, the researchers reported that solriamfetol, armodafinil-modafinil, and pitolisant-H3-autoreceptor blockers effectively reduced daytime sleepiness in patients with OSA already on conventional therapies, with solriamfetol likely being the most effective.

In addition, the authors noted that adverse events (AEs) likely increased the risk of discontinuation with armodafinil-modafinil and possibly increased the risk with solriamfetol.

Solriamfetol, Armodafinil-Modafinil, or Pitolisant

The network meta-analysis included 14 trials published to the Medline, Central, Embase, and ClinicalTrials.gov databases by November 2022. The pooled cohort consisted of 3085 patients with EDS-associated OSA who were on or eligible for conventional therapy and assigned to any pharmacological treatment.

Compared with placebo at week 4, authors found Epworth Sleepiness Scale scores were probably improved by:

• Solriamfetol (mean difference [MD], –3.85; 95% CI, –5.24 to –2.50; high certainty)
• Armodafinil-modafinil (MD, –2.25; 95% CI, –2.85 to –1.64; moderate certainty)
• Pitolisant-H3-autoreceptor blockers (MD, –2.78; 95% CI, –4.03 to –1.51; moderate certainty)

Compared with placebo at week 4, mean maintenance of wakefulness test (MWT) scores were also improved with high certainty by both solriamfetol (standardized MD [SMD], 0.9; 95% CI, 0.64-1.17) and armodafinil-modafinil (SMD, 0.41; 95% CI, 0.27-0.55), whereas pitolisant-H3-autoreceptor blockers probably did not improve MWT (moderate certainty).

Researchers found that AEs increased risk for discontinuation with moderate certainty for armodafinil-modafinil (relative risk [RR], 2.01; 95% CI, 1.14-3.51) and with low certainty for solriamfetol (RR, 2.07; 95% CI, 0.67-6.25). The lower degree of certainty led authors to suggest these 2 treatments may not increase the risk for serious AEs.

In closing, the study’s authors noted their findings were limited by the lack of data on long-term efficacy or efficacy among patients who had mixed or nonadherence to conventional treatments for OSA.

Ultimately, the authors concluded that all 3 agents effectively reduced daytime sleepiness in patients, with solriamfetol likely being the optimal choice.

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