Solriamfetol improves cognitive function in OSA, excessive daytime sleepiness
Key takeaways:
- Using baseline scores as reference points, three measures of cognitive function improved more when patients took solriamfetol vs. placebo.
- Reported adverse events did not exceed the moderate severity level.
Among patients with obstructive sleep apnea and excessive daytime sleepiness-related cognitive impairment, 2-week solriamfetol led to cognitive function improvement on three tests/scales, according to data published in CHEST.
“These results support previous findings that solriamfetol improves [excessive daytime sleepiness (EDS)] in patients with OSA, has a favorable safety profile, and has the potential to improve cognitive function in patients with cognitive impairment associated with OSA and EDS,” Hans P. A. Van Dongen, PhD, professor and director of the sleep and performance research center at Washington State University’s Elson S. Floyd College of Medicine, and colleagues wrote.
In the multicenter, randomized, double-blind, placebo-controlled, crossover, phase 4 SHARP trial, Van Dongen and colleagues evaluated 59 patients (mean age, 52.2 years; 36% women; 73% white; 71% PAP users) with cognitive impairment associated with OSA and EDS to uncover the impact of 2-week solriamfetol (Sunosi, Axsome Therapeutics) vs. placebo on cognitive function, measured via the Digit Symbol Substitution Test of the Repeatable Battery for the Assessment of Neuropsychological Status (DDST RBANS).
As Healio previously reported, solriamfetol, pitolisant (Wakix, Harmony Bioscience) and armodafinil-modafinil reduced EDS in patients with OSA who are already receiving conventional therapy, with solriamfetol being “likely superior.”
When receiving solriamfetol, patients started with a once-daily 75 mg dose for 3 days, followed by a once-daily 150 mg dose for the rest of the 2-week period. Between the switch from solriamfetol to placebo (n = 30) or vice versa (n = 29), there was a 1-week washout period, according to the study.
“Two participants (one in each treatment sequence) did not complete the study; one completed the first period efficacy visit, resulting in 58 participants in the modified intention-to-treat population with data available for analysis of efficacy outcomes,” Van Dongen and colleagues wrote.
Using the baseline DSST RBANS scores as the reference point, researchers found a better average DSST RBANS score after patients received solriamfetol vs. placebo (mean difference, 1.75; 95% CI, 0.46-3.04).
Notably, the significant improvement observed with solriamfetol vs. placebo was found at three of the four time points assessed shortly following dosing: 2 hours (mean difference, 1.91; 95% CI, 0.16-3.65), 6 hours (2.33; 95% CI, 0.78-3.88) and 8 hours (1.58; 95% CI, 0.23-2.93).
Other measures of cognitive function that improved more from baseline when patients took solriamfetol vs. placebo included the British Columbia Cognitive Complaints Inventory (mean difference, –1.58; 95% CI, –2.53 to –0.63) and the Patient Global Impression of Severity (mean difference, –0.29; 95% CI, –0.57 to –0.02), according to the study.
Researchers also reported on change in Epworth Sleepiness Scale score from baseline and found significant improvements with solriamfetol vs. placebo at the end of the treatment period (mean difference, –2.1; 95% CI, –3.51 to –0.68).
In terms of safety, more patients reported a treatment-emergent adverse event when receiving solriamfetol vs. placebo (19%; n = 11 vs. 10%; n = 6). The study noted that reported adverse events did not exceed the moderate severity level.
Nausea was the treatment-emergent adverse event experienced by the highest proportion of patients during solriamfetol treatment at 7% (n = 4). Anxiety was reported by a lower proportion of patients (3%; n = 2) but was still notable, according to the study.
“Research is needed to evaluate cognitive improvements from solriamfetol compared with other [wake-promoting agents],” Van Dongen and colleagues wrote.
Perspective
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The idea that neurologic and neurocognitive consequences can doggedly persist in patients with OSA despite treatment, including in patients adherent to PAP therapy, is well known and important. Further, these consequences of OSA represent a large unmet need.
The authors in this study present a randomized, double-blind, placebo-controlled, crossover trial studying the effects of solriamfetol on both daytime sleepiness and neurocognitive outcomes with promising results.
Solriamfetol represents one of the newer wake-promoting agents with a unique mechanism of action — dopamine and norepinephrine reuptake inhibition. The authors also note another intriguing mechanism, agonism of trace amine-associated receptor 1, which may have benefits on cognitive functioning and may help to explain some of the positive effects seen in this study.
Among the strengths of this trial was use of multiple endpoints on repeatable neurocognitive testing over 2-hour intervals, up to 8 hours, in a single day. The persistence of positive effects on this test, as the authors note, would cover a large portion of wakefulness during an average day, which represents real-world relevance.
Further, no treatment-emergent adverse effects were noted to be severe or lead to removal from or discontinuation of the study, implying this type of treatment might be well tolerated.
However, it should be noted that 19% of the treatment group reported side effects compared with 10% of placebo, and whether such side effects would outweigh the benefits of treatment over the long term cannot be addressed with this study design.
One limitation of this study was that it tested a short-term treatment trial — 2 weeks — and measured potential benefit on a single day. Therefore, it is difficult to project whether the positive treatment effects seen in this study would persist over the long term.
However, these findings certainly warrant additional longer-term studies and represent a positive and important step in the treatment of persistent neurocognitive deficits due to OSA.
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