Nurses arriving for a 5 a.m. shift. Warehouse workers clocking in at 4. Bakers, airport staff, and first responders starting before sunrise. Roughly 16 to 20 percent of the U.S. workforce performs shift work, and those with the earliest start times — between 3 and 7 a.m. — are among the most likely to develop shift work disorder, a condition marked by chronic excessive sleepiness and impaired functioning.
Until now, not a single randomized clinical trial had tested a treatment for this specific group. A study published in NEJM Evidence changes that.
The Trial
Researchers at Mass General Brigham enrolled 78 early-morning shift workers diagnosed with shift work disorder in a randomized, double-blind, placebo-controlled trial. Participants worked shifts starting between 3 and 7 a.m. and took either solriamfetol (marketed as Sunosi) or a placebo on workdays for four weeks.
Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor already approved for treating excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea. This trial tested whether it could also help the distinct problem of circadian-misaligned sleepiness in shift workers.
The Results
After four weeks, the differences were clear across every measure:
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Objective alertness: Participants on solriamfetol stayed awake 9.4 minutes longer on the Maintenance of Wakefulness Test compared to placebo (P<0.001) — a clinically meaningful difference in a controlled, low-stimulation setting designed to measure the ability to resist sleep.
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Subjective sleepiness: Scores on the Karolinska Sleepiness Scale improved by 1.2 points more than placebo, reflecting how much more alert participants felt during their shifts.
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Clinician assessment: Doctors rated solriamfetol patients as 3.7 times more likely to have meaningfully improved compared to placebo.
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Patient self-assessment: Workers themselves rated their odds of improvement at 4.2 times higher than placebo, reporting better work performance and greater ability to manage daily tasks.
Participants on solriamfetol were able to maintain alertness throughout a full eight-hour shift — a result with direct implications for both productivity and safety.
A Favorable Safety Profile
Adverse events were actually slightly more common in the placebo group (63%) than in the solriamfetol group (55%). When side effects did occur with solriamfetol, headache and nausea were the most frequently reported. No serious adverse events were attributed to the drug.
Critically, solriamfetol did not appear to disrupt sleep when participants were off-shift. Unlike older stimulant-type medications, the drug's mechanism — boosting dopamine and norepinephrine reuptake inhibition — wears off within hours, allowing normal sleep during off-duty periods.
Why Early-Morning Workers Were Overlooked
Shift work disorder has historically been studied in the context of overnight shifts, where the circadian disruption is most extreme. But early-morning workers face their own biological challenge: waking at 2 or 3 a.m. means beginning work during the circadian nadir, the period when the brain's drive for sleep is strongest.
These workers often cannot simply "go to bed earlier" to compensate. The body's circadian clock resists falling asleep in the early evening, and social and family obligations further constrain sleep timing. The result is chronic partial sleep deprivation layered on top of circadian misalignment — a combination that degrades alertness, mood, and cognitive function.
The consequences extend beyond individual discomfort. Sleepy shift workers face elevated risks of workplace accidents, motor vehicle crashes, and medical errors. A 2020 meta-analysis estimated that shift work disorder affects between 10 and 38 percent of shift workers, depending on the population studied.
What Comes Next
The research team is currently recruiting for a follow-up trial of solriamfetol in overnight shift workers, which could support broader FDA approval for shift work disorder as an indication. Solriamfetol is currently approved only for narcolepsy and obstructive sleep apnea-related sleepiness; use for shift work disorder would be off-label until further regulatory action.
What This Means for Patients
Early-morning shift workers who struggle with persistent sleepiness during their shifts — despite adequate sleep opportunity — should consider discussing shift work disorder with a sleep specialist. The condition is formally diagnosable and, as this trial demonstrates, treatable.
For workers already aware of their condition, the study offers evidence that pharmacological support can make a meaningful difference in both alertness and daily functioning. The conversation with a physician should include discussion of sleep hygiene optimization, shift scheduling where possible, and strategic light exposure — alongside the option of medication for cases where behavioral strategies alone fall short.
