Solriamfetol (Sunosi), a norepinephrine reuptake inhibitor, is likely more effective than other wakefulness-promoting drugs in patients with obstructive sleep apnea (OSA) who have residual daytime sleepiness after conventional treatment, according to a systematic review and meta -analyses.
In a systematic review of 14 studies including more than 3,000 patients, solriamfetol was associated with improvements of 3.85 points on the Epworth Sleepiness Scale (ESS) score compared to placebo.
“We found that solriamfetol is nearly twice as effective as modafinilarmodafinil, the cheapest and oldest option at improving ESS score, and much more effective at improving Test of Maintained Wakefulness (MWT),” study author Tyler Pitre, MD, an internal medicine physician at McMaster University in Hamilton, Canada, said Medscape Medical News.
The results were published online on May 9 Annals of Internal Medicine.
High certainty evidence
The analysis included 3085 adults with excessive daytime sleepiness (EDS) who were receiving or were eligible for conventional OSA treatment such as positive airway pressure (PAP). Participants were randomly assigned to receive placebo or any EDS pharmacotherapy (armodafinil, modafinil, solriamfetol, or pitolisant). The primary outcomes of the analysis were change in ESS and MWT. Secondary outcomes were drug-related adverse events.
The studies had an average follow-up time of 4 weeks. The meta-analysis showed that solriamfetol improved ESS to a greater extent than placebo (high certainty), armodafinilmodafinil and pitolisant (moderate certainty). Compared with placebo, the mean difference in ESS scores for solriamfetol, armodafinilmodafinil and pitolisant were 3.85, 2.25 and 2.78, respectively.
The analysis produced high-certainty evidence that solriamfetol and armodafinilmodafinil improved MWT, compared with placebo. The former was “probably superior,” while pitolisant “may have little or no effect on MWT, compared with placebo,” the authors write. The standardized mean difference (SMD) in MWT scores, relative to placebo, was 0.90 for solriamfetol and 0.41 for armodafinilmodafinil. “Solriamfetol is likely superior to armodafinilmodafinil in improving MWT (SMD, 0.49),” state the authors.
Compared with placebo, armodafinilmodafinil probably increases the risk of discontinuation due to adverse events (relative risk [RR], 2.01) and solriamfetol may increase the risk of discontinuation (RR, 2.04), according to the authors. Pitolisant “may have little or no effect on drug withdrawal due to adverse events,” the authors write.
While solriamfetol may have led to more discontinuations than armodafinilmodafinil, “we found no compelling evidence of serious adverse events, albeit with very short-term follow-up,” they add.
The most common side effects for all surgeries were headache, insomnia and anxiety. Headache was more likely with armodafinilmodafinil (RR, 1.87) and insomnia was more likely with pitolisant (RR, 7.25).
“Although solriamfetol appears to be the most effective, hypertension and associated costs may be a barrier to its use,” say the researchers. “In addition, there are potentially effective candidate therapies such as methylphenidate, atomoxetine or caffeine, which have not been examined in randomized clinical trials.”
Although EDS is reported in 40% 58% of patients with OSA and can persist in 6% 18% despite PAP therapy, most non-sleep specialists may not be aware of drug options, Pitre said. “I haven’t seen a study looking at physicians’ prescribing habits for this condition, but I suspect primary care physicians aren’t prescribing modafinilarmodafinil as frequently for it, and less so for solriamfetol,” she said. “I hope this document will raise awareness of this condition and also inform doctors about the options available to patients, as well as common side effects to advise them on before starting treatment.”
Pitre was surprised by the extent of solriamfetol’s superiority over modafinilarmodafinil, but cautioned that solriamfetol has been shown to increase blood pressure at higher doses. Therefore it needs to be prescribed carefully, “especially to a patient population who often have comorbid hypertension,” he said.
Some limitations of the analysis were that all studies were conducted in high-income countries (most commonly the United States). Additionally, 77% of the participants were white and 71% were male.
Beneficial adjunctive therapy
Commenting on the findings for Medscape, Sogol Javaheri, MD, MPH, who was not involved in the research, said they confirm those of previous studies and are “consistent with what my colleagues and I experience in our clinical practices.”
Javaheri is director of the sleep medicine fellowship associate program at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston.
While sleep medicine specialists are more likely than others to prescribe these medications, “any physician can use these medications, ideally if they’ve ruled out other potential reversible causes of EDS,” Javaheri said. “Medications don’t treat the underlying cause, which is why it’s important to use them as an adjunct to conventional therapy that actually treats the underlying sleep disorder and to rule out additional potential causes of sleepiness that are treatable.”
These potential causes could include insufficient sleep (less than 7 hours a night), untreated anemia and incompletely treated sleep disturbances, he explained. In sleep medicine, modafinil is usually the treatment of choice due to its lower cost, but it can reduce the effectiveness of hormonal contraception. Solriamfetol, on the other hand, doesn’t. “Also, I look forward to the validation of pitolisant for the treatment of EDS in patients with OSA, as it is not a controlled substance and may benefit patients with a history of substance abuse or who may be at increased risk of addiction,” Javaheri said.
The study was conducted without external funding. Pitre and Javaheri report no relevant financial relationships.
Ann Intern Med. Published online May 9, 2023. Abstract
Kate Johnson is a Montreal-based freelance medical journalist who has written on all areas of medicine for more than 30 years.
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