Solriamfetol (Sunosi), a norepinephrine–dopamine reuptake inhibitor, might be more practical than different wakefulness-promoting drugs in sufferers with obstructive sleep apnea (OSA) who’ve residual daytime sleepiness after standard remedy, in keeping with a scientific overview and meta-analysis.
In a scientific overview of 14 trials that included greater than 3000 sufferers, solriamfetol was related to enhancements of three.85 factors on the Epworth Sleepiness Scale (ESS) rating, in contrast with placebo.
“We discovered that solriamfetol is nearly twice as efficient as modafinil–armodafinil — the cheaper, older possibility — in bettering the ESS rating and way more efficient at bettering the Upkeep of Wakefulness Check (MWT),” research creator Tyler Pitre, MD, an inner drugs doctor at McMaster College in Hamilton, Canada, advised Medscape Medical Information.
The findings were published on-line Might 9 in Annals of Inner Medication.
Excessive-Certainty Proof
The evaluation included 3085 adults with extreme daytime sleepiness (EDS) who had been receiving or had been eligible for standard OSA remedy corresponding to optimistic airway strain (PAP). Contributors had been randomly assigned to both placebo or any EDS pharmacotherapy (armodafinil, modafinil, solriamfetol, or pitolisant). The first outcomes of the evaluation had been change in ESS and MWT. Secondary outcomes had been drug-related antagonistic occasions.
The trials had a median follow-up time of 4 weeks. The meta-analysis confirmed that solriamfetol improves ESS to a better extent than placebo (excessive certainty), armodafinil–modafinil, and pitolisant (reasonable certainty). In contrast with placebo, the imply distinction in ESS scores for solriamfetol, armodafinil–modafinil, and pitolisant was −3.85, −2.25, and −2.78, respectively.
The evaluation yielded high-certainty proof that solriamfetol and armodafinil–modafinil improved MWT, in contrast with placebo. The previous was “most likely superior,” whereas pitolisant “could have little to no impact on MWT, in contrast with placebo,” write the authors. The standardized imply distinction (SMD) in MWT scores, in contrast with placebo, was 0.90 for solriamfetol and 0.41 for armodafinil–modafinil. “Solriamfetol might be superior to armodafinil–modafinil in bettering MWT (SMD, 0.49),” say the authors.
In contrast with placebo, armodafinil–modafinil most likely will increase the chance for discontinuation as a consequence of antagonistic occasions (relative threat [RR], 2.01), and solriamfetol could improve the chance for discontinuation (RR, 2.04), in keeping with the authors. Pitolisant “could have little to no impact on drug discontinuations as a consequence of antagonistic occasions,” write the authors.
Though solriamfetol could have led to extra discontinuations than armodafinil–modafinil, “we didn’t discover convincing proof of great antagonistic occasions, albeit with very short-term follow-up,” they add.
The commonest uncomfortable side effects for all interventions had been complications, insomnia, and nervousness. Complications had been almost certainly with armodafinil–modafinil (RR, 1.87), and insomnia was almost certainly with pitolisant (RR, 7.25).
“Though solriamfetol seems simplest, comorbid hypertension and prices could also be boundaries to its use,” say the researchers. “Moreover, there are doubtlessly efficient candidate therapies corresponding to methylphenidate, atomoxetine, or caffeine, which haven’t been examined in randomized medical trials.”
Though EDS is reported in 40%–58% of sufferers with OSA and might persist in 6%–18% regardless of PAP remedy, most non-sleep specialists will not be conscious of pharmacologic choices, mentioned Pitre. “I’ve not seen a research that appears on the prescribing habits of physicians for this situation, however I think that main care physicians should not prescribing modafinil–armodafinil steadily for this, and fewer so for solriamfetol,” he mentioned. “I hope this paper builds consciousness of this situation and likewise informs clinicians on the choices accessible to sufferers, in addition to frequent uncomfortable side effects to counsel them on earlier than beginning remedy.”
Pitre was shocked on the magnitude of solriamfetol’s superiority to modafinil–armodafinil however cautioned that solriamfetol has been proven to extend blood strain in increased doses. It subsequently have to be prescribed rigorously, “particularly to a inhabitants of sufferers who usually have comorbid hypertension,” he mentioned.
Some limitations of the evaluation had been that each one trials had been carried out in high-income international locations (mostly america). Furthermore, 77% of members had been White, and 71% had been male.
Useful Adjunctive Remedy
Commenting on the findings for Medscape, Sogol Javaheri, MD, MPH, who was not concerned within the analysis, mentioned that they verify these of prior research and are “in keeping with what my colleagues and I expertise in our medical practices.”
Javaheri is affiliate program director of the sleep drugs fellowship at Brigham and Girls’s Hospital and assistant professor of Medication at Harvard Medical College in Boston.
Whereas sleep drugs specialists are extra doubtless than others to prescribe these drugs, “any clinician could use these drugs, ideally if they’ve dominated out different potential reversible causes of EDS,” mentioned Javaheri. “The drugs don’t deal with the underlying trigger, which is why it is necessary to make use of them as an adjunct to standard remedy that really treats the underlying sleep disorder and to rule out further potential causes of sleepiness which might be treatable.”
These potential causes would possibly embrace inadequate sleep (lower than 7 hours per evening), untreated anemia, and incompletely handled sleep problems, she defined. In sleep drugs, modafinil is often the remedy of alternative due to its decrease price, however it might scale back the efficacy of hormonal contraception. Solriamfetol, nonetheless, doesn’t. “Moreover, I stay up for validation of pitolisant for remedy of EDS in OSA sufferers, as it’s not a managed substance and should profit sufferers with a historical past of substance abuse or who could also be at increased threat of habit,” mentioned Javaheri.
The research was carried out with out outdoors funding. Pitre and Javaheri report no related monetary relationships.
Ann Intern Med. Printed on-line Might 9, 2023. Abstract
Kate Johnson is a Montreal-based freelance medical journalist who has been writing for greater than 30 years about all areas of drugs.
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