First-of-Its-Kind Study Finds Drug Reduces Excessive Sleepiness in Early-Morning Workers

A clinical trial suggests that a wake-promoting drug may help early-morning shift workers overcome the biological challenges of working during hours when the brain expects sleep.

Before sunrise, millions of people are already at work. For many of them, the biggest challenge is not motivation. It is biology. Early morning shifts are more common than overnight schedules, yet many workers on these shifts struggle with the extreme sleepiness linked to shift work disorder. That can hurt concentration, job performance, and safety.

A new clinical trial from Mass General Brigham suggests there may be a way to help. Researchers found that solriamfetol (Sunosi), a wake-promoting drug, improved alertness in early morning shift workers with shift work disorder. The findings were published in NEJM Evidence.

“Until now, no clinical trial had tested a treatment for shift work disorder in early-morning shift workers, even though this is the most common type of shift schedule,” said senior author Charles A. Czeisler, PhD, MD, chief and senior physician of the Division of Sleep and Circadian Medicine in the Mass General Brigham Department of Medicine. “This study addresses a major gap by focusing on the workers who start their day when most people are still asleep.”

About one in four workers has a schedule that falls outside the traditional 9-to-5 day. That includes many people who start work well before dawn. Researchers say these workers often do not think of themselves as “shift workers.” They may see their schedule as an unusually early version of a normal workday. Even so, many are still vulnerable to shift work disorder, a condition marked by disrupted sleep and excessive daytime sleepiness.

The Biological Challenge of Early Starts

“People who start work between 3 a.m. and 7 a.m. are waking up at a time when the brain is biologically programmed to sleep. That makes staying alert extraordinarily difficult, even when they are highly motivated,” said first author Kirsi-Marja Zitting, PhD, an investigator with the Division of Sleep and Circadian Medicine in the Mass General Brigham Department of Medicine. “They are often dealing with a double burden—excessive sleepiness during work hours and difficulty sleeping enough when they have the chance to rest.”

Shift work disorder can increase the risk of impaired thinking, reduced job performance, motor vehicle crashes, and workplace accidents. Doctors sometimes prescribe wake-promoting medications such as modafinil to help manage the condition. However, those drugs were mainly studied in overnight shift workers and may interfere with sleep later in the day.

Solriamfetol, the medication tested in the new study, is already approved to treat excessive sleepiness in people with obstructive sleep apnea and narcolepsy. Researchers considered it a promising option for early morning workers because it can promote wakefulness for several hours without significantly reducing sleep later.

The clinical trial included 78 early morning shift workers who met the criteria for shift work disorder. Half of the participants took solriamfetol on each workday for four weeks, while the other half received a placebo.

Researchers evaluated how long participants could remain awake in a quiet, dark setting during periods that matched their normal working hours. Participants also met with physicians and reported on their daily functioning.

Improved Alertness and Work Function

After four weeks, the group taking solriamfetol reported significantly less sleepiness and remained awake longer during simulated work hours. Both participants and their doctors also noted improvements in overall functioning, work productivity, and daily activities.

“The improvement we saw is clinically meaningful. These workers were able to stay awake and alert throughout a full eight-hour shift, which has real implications for performance, safety, and quality of life,” Czeisler said. “Shift workers are essential to how our society functions, yet they often pay a hidden biological cost. This study shows we can do better for them.”

The researchers note that early morning shift workers have not been widely studied. In addition, the four week trial involved otherwise healthy adults, so the long term effects of the treatment still need further investigation.

The team is now recruiting participants for a follow-up clinical trial that will test solriamfetol in overnight shift workers, which could help support approval of the drug as a treatment for shift work disorder.

Reference: “Solriamfetol for Excessive Sleepiness in Early-Morning Shift Work Disorder” by Kirsi-Marja Zitting, Katherine R. Gilmore, Brandon J. Lockyer, Eileen B. Leary, Wei Wang, Nicolas C. Issa, Stuart F. Quan, Jonathan S. Williams, Jeanne F. Duffy and Charles A. Czeisler, 27 January 2026, New England Journal of Medicine.
DOI: h10.1056/EVIDoa2500190

Funding: Funded by Jazz Pharmaceuticals, Axsome Therapeutics, and Brigham and Women’s Hospital Center for Clinical Investigation; NCT04788953(2021-03-09) https://clinicaltrials.gov/study/NCT04788953

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