Mass General Brigham researchers found that solriamfetol helped early morning shift workers with shift work disorder stay more alert
Many more people work very early morning shifts than overnight ones, and a large proportion struggle with excessive sleepiness from shift work disorder, leading to problems with focus, performance and safety. A new clinical trial by investigators from Mass General Brigham found that the wake-promoting drug solriamfetol (Sunosi) helped early morning shift workers with shift work disorder stay more alert. Their results are published this week 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 a quarter of the workforce labors outside the traditional 9-to-5 schedule, including early-morning shifts. Researchers say many people who start work very early do not think of themselves as "shift workers" and may view their schedules as an early start to a normal workday. Yet, many are at risk of developing shift work disorder, a medical condition characterized by sleep disturbances and excessive daytime sleepiness.
"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."
People with shift work disorder face higher risks of impaired thinking, reduced job performance, motor vehicle crashes and workplace accidents. Wake-promoting drugs such as modafinil are commonly used for shift work disorder but were only tested in overnight shift workers and can make it harder to sleep later in the day.
The drug in this study, solriamfetol, is approved to treat excessive sleepiness in people with obstructive sleep apnea and narcolepsy. Its ability to keep people awake for hours—without costing them sleep later—made it a logical option to test in early-morning shift workers, the researchers said.
The study enrolled 78 early-morning shift workers who met criteria for shift work disorder. Half took solriamfetol each workday for four weeks, and half took a placebo. Researchers measured how long the workers could stay awake in a quiet, dark environment during times when they would normally be working. They also met with doctors and gave reports of their daily functioning.
After four weeks, workers who received solriamfetol were significantly less sleepy and were able to stay awake longer during simulated work hours. Both the workers and their doctors reported better 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 are not well studied, and that the four-week study focused on otherwise healthy adults, meaning longer-term effects still need to be explored. The team is currently recruiting for a follow-up clinical trial of solriamfetol in overnight shift workers to support its approval as a treatment for shift work disorder.
Authorship: In addition to Zitting and Czeisler, Mass General Brigham authors include Katherine R. Gilmore, Brandon J. Lockyer, Wei Wang, Nicolas C. Issa, Stuart F. Quan, Jonathan S. Williams, and Jeanne F. Duffy. Additional authors include Eileen B. Leary.
Disclosures: A full list of author disclosures can be found in the paper. All authors received financial support from Jazz and Axsome. Leary was employed by Jazz and later Axsome and other authors received financial support via a grant awarded to Brigham and Women's Hospital.
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
Paper cited: Zitting KM et al." Solriamfetol for Excessive Sleepiness in Early Morning Shift Work Disorder" New England Journal of Medicine DOI: 10.1056/EVIDoa2500190
