Solriamfetol Significantly Reduces Excessive Sleepiness in Shift Work Disorder, Study Shows

A randomized, double-blind, placebo-controlled trial (NCT04788953) evaluated the efficacy of solriamfetol (Sunosi; Axsome Therapeutics) in early-morning shift workers with shift work disorder (SWD) and found that treatment significantly improved excessive sleepiness compared with placebo. After 4 weeks, the selective dopamine and norepinephrine reuptake inhibitor was associated with improvements in subjective sleepiness as well as clinician- and patient-reported ratings.¹

Trial Overview

Published in NJEM Evidence, the study enrolled 78 early-morning shift workers aged 18 to 64 years with SWD who worked at least 20 hours per week in shifts lasting 6 to 12 hours that began between 3:00 and 7:00 am for at least 3 days per week. The trial focued specifically on early morning shift workers so night, rotating, and irregular shift workers were excluded.

The primary endpoint was change in objective sleepiness, measured by sleep latency on the Maintenance of Wakefulness Test (MWT). Secondary outcomes included subjective sleepiness assessed by the Karolinska Sleepiness Scale (KSS) as well as clinician- and patient-assessed change in clinical condition, using the Clinical Global Impression of Change and Patient Global Impression of Change scales.

Clinical Outcomes

Results demonstrated that patients treated with solriamfetol were significantly less sleepy than those treated with placebo, with a 9.4-minute longer sleep latency on the MWT (95% CI, 5.7 - 13.0; P <0.001). Additionally, treatment was also associated with improvements in subjective sleepiness (KSS difference, −1.2; 95% CI, −1.7 to −0.7), and higher odds of improvement on clinician-rated (odds ratio [OR] 3.7; 95% CI, 1.3 to 10.4) and patient-rated ([OR], 4.2; 95% CI, 1.5 to 11.6) assessments.

Led by Kirsi-Marja Zitting, PhD, clinical investigator at Brigham and Women’s Hospital and Harvard Medical School, the study found that 55% of patients treated with solriamfetol and 63% of those receiving placebo reported at least 1 adverse event (AE). The most common AEs were headache and nausea.

Study Limitations

Zitting and her colleagues reported that although the trial is strong, multiple limitations exist. The demographics related to early-morning shift work are not well understood, making it difficult to determine whether our trial population reflects the overall population of early-morning shift workers with SWD. Furthermore, the participants were selected to have minimal comorbidities, which may not be reflective of early-morning shift workers overall. Although the participants had to report obtaining a typical night of sleep prior to the MWT, they did not undergo a monitored PSG prior to the test.

“Because the patients in our trial worked in a variety of industries, objective measures of work performance were not assessed,” noted study authors. “However, we did use a validated instrument to assess subjective work performance, and we found that the patients treated with solriamfetol reported greater work productivity and less functional impairment due to sleepiness at work than those who received placebo.”¹

Watch more: Solriamfetol for Treatment of EDS in Patients With OSA

Recent Literature on Solriamfetol

Previously reported results involving solriamfetol indicated improvements in a number of neuropsychological outcomes among patients with obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS). Findings from the SURWEY study, a real-world, retrospective, observational trial, showed that treatment with solriamfetol reduced EDS, although there was no link between changes in OSA-associated cognitive impairment and EDS.²

Presented at the 2025 SLEEP Annual Meeting, held June 8-11 in Seattle, Washington, data were analyzed using repeated measures ANOVA, and the relationship between changes in EDS and cognition was assessed through regression analysis. After 3 months of treatment with solriamfetol, participants experienced a 11.4% mean improvement in TAP scores, with statistically significant values (P <.01) observed for those with a warning signal (237.7 [±21.4]) and those without (239.5 [±21.3]).

Led by Yaroslav Winter, MD, MSc, head of Mainz Comprehensive Epilepsy and Sleep Medicine Center, Johannes Gutenberg University, solriamfetol-treated patients also showed a 40.8% (5.1 [±3.1]; P <.01) mean improvement in BC-CCI and a 30.6% (9.3 [±1.8]; P <.01) mean improvement in WAIS-IV across the 3-month period. Notably, patients also saw enhancements in Epworth Sleepiness Scale, demonstrated by score changes of 4.7 (±2.7; P <.01).

REFERENCES
1. Zitting KM, Gilmore KR, Lockyer BJ, et al. Solriamfetol for Excessive Sleepiness in Early-Morning Shift Work Disorder. NEJM Evid. 2026;5(2):EVIDoa2500190. doi:10.1056/EVIDoa2500190
2. Winter Y, Eglit GML, Floam S, Kallweit U. Effects of solriamfetol on neuropsychological outcomes in patients with obstructive sleep apnea in the real-world SURWEY study. Presented at: 2025 SLEEP Annual Meeting; June 8-11; Seattle, Washington. ABSTRACT 0784