Sunosi 'likely superior' treatment for daytime sleepiness in patients with sleep apnea

Key takeaways:

• Wakefulness-promoting agents appear to reduce excessive daytime sleepiness in patients with obstructive sleep apnea.
• However, patients may discontinue the medications due to adverse events.

Sunosi, Wakix and armodafinil-modafinil reduced excessive daytime sleepiness in patients with obstructive sleep apnea who are already receiving conventional therapy, with Sunosi being “likely superior,” according to researchers.

However, the study showed that many patients may discontinue these medications due to adverse events such as headache, anxiety and insomnia.

Excessive daytime sleepiness (EDS) is common in patients with obstructive sleep apnea (OSA), which affects about a quarter of people in the United States, Tyler Pitre, MD, MA, an internal medicine resident in the department of medicine at McMaster University in Ontario, Canada, and colleagues wrote in Annals of Internal Medicine.

EDS, which is linked to neuropsychological impairment and decreased quality of life, usually improves with standard therapies such as positive airway pressure to treat the underlying airway obstruction, according to Pitre and colleagues. But EDS persists in 6% to 18% of patients despite optimal OSA management.

“Interventions aimed at reducing EDS are an important priority for clinicians,” the researchers wrote.

However, not much is known about the comparative effectiveness of pharmacologic agents.

“Pharmacologic treatment of OSA-associated EDS varies by jurisdiction but may include the use of armodafinil-modafinil, as well as newer agents including [Sunosi (solriamfetol; Jazz Pharmaceuticals)], a norepinephrine-dopamine reuptake inhibitor,” the researchers wrote. “Armodafinil-modafinil and solriamfetol are both schedule IV medications approved for OSA in the U.S.”

Additionally, Wakix (pitolisant; Harmony Bioscience), which is a histamine-3 (H3) autoreceptor blocker, has been studied for OSA-associated EDS. Currently, it is approved for narcolepsy but not OSA.

“It promotes wakefulness by blocking the autoinhibiting activity of histamine — a molecule associated with wakefulness — and H3 receptor agonists on endogenous histamine release, allowing for above-basal levels,” the researchers wrote.

Pitre and colleagues conducted a systematic review and network meta-analysis to compare the effectiveness of drugs for EDS in OSA.

The researchers evaluated 14 trials including 3,085 participants with EDS-associated OSA who were on or eligible for conventional therapy. Paired reviewers independently extracted the data that addressed the drugs’ effects on the Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT) and adverse events at the longest reported follow-up visit. The researchers then used the GRADE approach to assess the certainty of evidence.

Pitre and colleagues found that for patients with OSA already on conventional therapy, solriamfetol, armodafinil-modafinil and pitolisant reduced daytime sleepiness, but solriamfetol was “likely superior.” However, they noted that adverse events such as anxiety, headache and insomnia increase the risk for discontinuation for these medications.

At 4 weeks, solriamfetol improved ESS scores compared with placebo (mean difference = 3.85; 95% CI, 5.24-2.5), the researchers determined with high certainty. Armodafinil-modafinil (mean difference = 2.25; 95% CI, 2.85-1.64) and pitolisant-H3-autoreceptor blockers (mean difference = 2.78; 95% CI, 4.03-1.51) also probably improve ESS scores, the researchers wrote. There was moderate certainty for this.

Additionally, at 4 weeks, solriamfetol (mean difference = 0.9; 95% CI, 0.64-1.17) and armodafinil-modafinil (mean difference = 0.41; 95% CI, 0.27-0.55) improved MWT compared with placebo. Both of these were high certainty. On the other hand, the researchers determined with moderate certainty that pitolisant-H3-autoreceptor blockers probably do not.

Finally, at the same time frame, the researchers determined with low certainty that solriamfetol may have increased the risk for discontinuation due to adverse events (RR = 2.07; 95% CI, 0.67-6.25) and determined with moderate certainty that armodafinil-modafinil probably increased the same risk (RR = 2.01; 95% CI, 1.14-3.51). However, low-certainty evidence suggested that the interventions might not increase the risk for serious adverse events.

“Future research should address potential long-term and rare harms that may be associated with these drugs and potential differential effects of these drugs in patients who are not adherent to conventional OSA treatment,” Pitre and colleagues concluded.