Citations

Abstract Introduction Zolpidem is a commonly prescribed FDA- approved hypnotic. In 2013, the FDA recommended reducing maximum dosing of zolpidem in female patients due to concern for slower elimination time as compared to their male counterparts. Despite this, none of the FDA warnings or communications cited published studies that support the claim that women are at increased risk of adverse events. Subsequent prescribing data has shifted to reflect FDA recommendations. In this study we examined risks of using above FDA recommended doses in female patients. Methods This is a retrospective chart review including all adult female patients (> 18 years old) evaluated and managed at the Mayo Clinic Center for Sleep Medicine between 1/1/2024 to 12/31/2024. Detailed review of Mayo Clinic’s EMR was accomplished with subjects on zolpidem split into supratherapeutic and non-supratherapeutic dosing groups. Subjects were relegated to the above maximum dose group if they were ever prescribed FDA-defined supratherapeutic dosing (>5 mg IR formulation or >6.25 mg ER formulation) for a >1 week period. Adverse events were defined as: falls, parasomnias, and cognitive impairment determined via ICD-10-CM codes that occurred at any period following zolpidem initiation. We analyzed rates of adverse effects using chi-square test of independence and Fischer’s exact test in patients with or without supratherapeutic dosing. Results 435 female patients met inclusion criteria. Among the demographic characteristics, only weight was associated with receiving a higher dose of zolpidem (P< 0.001). There were similar rates of adverse effects in both dosing groups with 11.4% of female patients on supratherapeutic dosing as compared to 10.9% of female patients on non-supratherapeutic dosing reporting adverse effects (chi-square test of independence (X2=6.5, N=435, p=0.99) or Fischer’s exact test (OR=1.05, p=0.87). Conclusion Overall, there was not a significant difference in rates of adverse events in female patients receiving supratherapeutic vs non-supratherapeutic doses of zolpidem during the time frame described. Further studies are warranted to better elucidate longitudinal risk of adverse effects related to gender-related differences with zolpidem dosing. Support (if any)

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)

Abstract Study Objectives Post-traumatic stress disorder (PTSD) and rapid eye movement (REM) sleep behavior disorder (RBD) share some common features including prominent nightmares and sleep disturbances. We aimed to comparatively analyze REM sleep without atonia (RSWA) between patients with chronic PTSD with and without dream enactment behavior (DEB), isolated RBD (iRBD), and controls. Methods In this retrospective study, we comparatively analyzed 18 PTSD with DEB (PTSD+DEB), 18 PTSD without DEB, 15 iRBD, and 51 controls matched for age and sex. We reviewed medical records to determine PTSD clinical features and quantitatively analyzed RSWA. We used nonparametric analyses to compare clinical and polysomnographic features. Results PTSD patients, both with and without DEB, had significantly higher RSWA than controls (all p < .025, excepting submentalis phasic duration in PTSD+DEB). Most RSWA measures were also higher in PTSD+DEB than in PTSD without DEB patients (all p < .025). Conclusions PTSD patients have higher RSWA than controls, whether DEB is present or not, indicating that REM sleep atonia control is abnormal in chronic PTSD. Further prospective studies are needed to determine whether neurodegenerative risk and disease markers similar to RBD might occur in PTSD patients.