Episode 1: Results of the Solriamfetol's effect on cognitive health

In this episode I will discuss the recent results of an industry funded randomized double bind placebo-controlled cross over trial comparing Solriamfetol to placebo in treating residual excessive daytime sleepiness and cognitive function in patients with treated obstructive sleep apnea published in Chest. Residual excessive daytime sleepiness despite adequate treatment of obstructive sleep apnea is common in patients with obstructive sleep apnea. Treatments for residual excessive daytime sleepiness despite obstructive sleep apnea (OSA) treatment include modafinil, armodafinil and solriamfetol.

This study was conducted from May 2021 to September 2022 at 28 sites in North America and Europe. The participants were 18 to 65 years old diagnosed with obstructive sleep apnea and impaired cognitive function defined as an age-corrected scaled score of < or = to 8 at screening on the Digit Symbol Substitution Test DSST, a subtest in the Wechsler Adult Intelligence Scale, 4th Edition (DSST WAIS-IV), and a score < or = 9 on the British Columbia Cognitive Complaints Inventory (BC-CCI) at screening and baseline.

Participants were included if they were consistent in the number of hours of PAP use on > or = to 5 nights per week for > or= to 1 month prior to baseline; or had no current PAP therapy for > or = to 1 month prior to baseline but a history of attempted PAP use for > or= to 1 month with > or = to 1 adjustment intended to optimize therapy; or had a history of surgical intervention intended to treat OSA symptoms. The participants were excluded if their usual bedtime was later than 1 am; they were a shift work; they used of over-the-counter or prescription medications that could affect excessive daytime sleepiness; any contraindication for solriamfetol; use of a PAP machine without down-loadable adherence data; diagnosis of a sleep disorder other than OSA; positive urine drug screen during the study; excessive caffeine use (>600 mg/d) 1 week prior to screening or anticipated during the study; and history or current diagnosis of any clinically relevant medical, behavioral, or psychiatric disorder associated with impaired cognitive function.

In this study the researchers randomized 59 patients to receive either placebo or solriamfetol 75 mg/d for 3 days, then 150 mg/d for 2 weeks. After a 1-week washout period, participants crossed over to receive the opposite intervention for 2 weeks. They measured the Digit Symbol Substitution Test (DSST), of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), the Patient Global Impression of Severity (PGI-s), and the Epworth Sleepiness Scale (ESS). The primary end point was change from baseline in average postdose Digit Symbol Substitution Test (DSST), of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Secondary end points were changes from baseline in Digit Symbol Substitution Test (DSST), of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), the Patient Global Impression of Severity (PGI-S), and the Epworth Sleepiness Scale (ESS) scores at 2, 4, 6, and 8 hours' postdose.

Solriamfetol was shown to significantly improve postpose average Digit Symbol Substitution Test (DSST), of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores compared to placebo (P=0.009). When evaluated at each 2-hour time point, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all, P values <0.05). During solriamfetol treatment, there were significant improvements in the British Columbia Cognitive Complaints Inventory (BC-CCI)(P value=0.002), Patient Global Impression of Severity (PGI-S) (P=0.034), and ESS(P=0.004) compared with placebo. The most common treatment-emergent adverse events were nausea at 7% and anxiety of 3%.

The researcher's conclusion were that solriamfetol can improve objective and subjective measures of cognitive function in patient with cognitive impairment associated with obstructive sleep apnea and excessive daytime sleepiness. Limitations of the study include its industry funding by the companies who own the rights to market solriamfetol. The authors list other limitations to include the 5-week duration of the study which precludes conclusions regarding the sustained effects on cognitive function over longer durations.

Overall I believe this study adds to the literature for treatment options for patients with residual excessive daytime sleepiness and cognitive impairments in patients with treated obstructive sleep apnea.