0759 Targeting Sleep Inertia in Sleep Disorders: A Retrospective Case Series of Evening-Dosed Extended-Release Methylphenidate

Abstract Introduction Sleep inertia—prolonged grogginess and confusion upon awakening—causes disabling impairment in hypersomnolence disorders, often persisting despite standard daytime stimulants. This leaves patients with functional limitations before medication onset. This case series evaluates evening-dosed, delayed-release methylphenidate for refractory sleep inertia. Methods A retrospective pre-post analysis was performed on a case series of 12 patients (age range: 12–24 years) treated for sleep disorders with residual sleep inertia. Diagnoses included idiopathic hypersomnia, circadian rhythm sleep-wake disorder, post-viral hypersomnia, and narcolepsy types 1 and 2. Patients were treated with evening-dosed delayed-release methylphenidate with final titrations ranging from 20 mg to 80 mg. Clinical metrics using validated sleep measures were collected to compare baseline (pre) and follow-up (post) metrics. The primary outcome was the Epworth Sleepiness Scale (ESS). Secondary outcomes included the Insomnia Severity Index (ISI), PROMIS Sleep-Related Impairment (SRI), Sleep Disturbance (SD), and the Clinical Global Impression (CGI) scale. Statistical significance of mean changes was assessed using paired sample t-tests. Results Evening-dosed long-acting methylphenidate improved sleepiness from 18.33 (SD=5.03) to 7.83 (SD=1.53) (reduction 10.50; 95% CI: 7.13–13.87; t=6.86, p< 0.0001). Patients achieved normalization (ESS< 11). Regarding secondary outcomes: PROMIS-SRI improved from 20.25 (SD=8.99) to 14.25 (SD=5.91) (Mean reduction 6.00; 95% CI: -12.17 to 24.17; t=1.05, p=0.37). ISI improved from 18.25 (SD=4.50) to 12.00 (SD=2.16) (Mean reduction 6.25; 95% CI: -0.40 to 12.90; t=2.99, p=0.06), suggesting no insomnia exacerbation. PROMIS-SD remained stable (18.43 [SD=9.91] to 16.14 [SD=6.12]; Mean reduction 2.29; 95% CI: -8.35 to 12.93; t=0.53, p=0.62). CGI-Sleep Inertia improved significantly from 3.00 (SD=0.00) to 1.56 (SD=0.53) (Mean reduction 1.44; 95% CI: 1.04–1.84; t=8.18, p< 0.0001), indicating minimal symptoms. Adherence was rated "good" or "acceptable." Conclusion This case series suggests that evening administration of delayed-release methylphenidate is associated with clinically significant reductions in daytime sleepiness and sleep inertia. A key limitation is that patients were concurrently treated with other stimulants or wake-promoting agents; thus, observed improvements likely reflect an additive benefit rather than an isolated effect. Findings suggest that targeting the morning "wake-up" phase with evening chronotherapy is a viable strategy for refractory sleep inertia in complex sleep disorders. Support (if any) None