Roberts, Jessica

Abstract Introduction Residual excessive daytime sleepiness (RES) despite effective positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) is a clinical problem impacting quality of life and daily function. Wake-promoting agents (WPAs) such as modafinil, armodafinil, and solriamfetol have demonstrated efficacy in reducing RES in randomized controlled trials (RCTs); however, their effectiveness in typical sleep clinic populations remains underexplored. This study aimed to evaluate the efficacy, safety, and tolerability of these WPAs in real-world clinical settings. Methods This retrospective study analyzed electronic health records of 69 randomly selected, consenting patients with OSA who are on PAP therapy and a WPA at Mayo Clinic from 9/19/2019 to 9/19/2024. Researchers reviewed charts for treatment indication, duration, adverse effects, and response (categorized as “complete,” “partial,” or “poor”). Therapy longevity was assessed using initiation, refill, and discontinuation data. Outcomes were analyzed with paired t-tests, chi-square tests, and regression models. Results Of 69 patients, 45 were excluded because: WPA use before observation period (24), off-label WPA use (13), WPA use before CPAP (3), or other (5). Off-label reasons included neurologic-condition-related fatigue (6), depression augmentation (5), and autoimmune-condition-related fatigue (2). 24 patients were on WPAs for RES with PAP-treated OSA, including 3 with mixed indications, and were included in analyses. The median age was 65 (IQR 11). BMI at OSA diagnosis was 33.6 (IQR 6.4). Most subjects were male (75%). Initial Epworth Sleepiness Scale scores (ESS) were 12.3±1.1. ESS at the first WPA prescription were 15.4±0.9 (p=0.04). Most patients (83.3%) started on modafinil. Of the 4 patients who started on armodafinil or solriamfetol, chart review showed a previous trial of modafinil without benefit. After optimizing the initial WPA dosage, ESS improved by 3.3±1.4 points (p=0.04) to 12.1 ±1.2. Side effects limited WPA use in 20.8% of patients. Median first WPA duration was 141 days (IQR 53-280) with no significant difference between these WPAs (p=0.81). Conclusion Although WPAs have narrowly defined approved indications, they are often prescribed off-label for comorbidities. Unlike straightforward use in RCTs, real-life use is more complicated. Patients prescribed WPAs for the targeted approved indication show statistically significant benefits, although adverse effects limited their use for some. Support (if any)