Clinical Trial Finds Solriamfetol Significantly Improves Alertness and Performance in Early Morning Shift Workers Suffering from Shift Work Disorder

The landscape of modern labor is increasingly defined by non-traditional hours, with approximately one-quarter of the global workforce operating outside the standard 9-to-5 window. Among these individuals, those who begin their duties in the early morning hours—typically between 3:00 a.m. and 7:00 a.m.—represent the largest yet most understudied segment of the shift-working population. A landmark clinical trial led by researchers at Mass General Brigham has now provided the first robust evidence for a pharmacological intervention specifically tailored to this demographic. The study, published in the journal NEJM Evidence, demonstrates that the wake-promoting agent solriamfetol, marketed under the brand name Sunosi, significantly enhances alertness and reduces excessive sleepiness in early morning shift workers diagnosed with shift work disorder (SWD).

This research addresses a critical gap in occupational medicine and sleep science. While previous pharmaceutical studies have focused predominantly on overnight or rotating shift workers, the millions of individuals who wake up while the rest of society is in deep sleep have remained largely overlooked. The findings suggest that solriamfetol could offer a vital tool for improving the safety, productivity, and quality of life for a workforce that includes essential personnel such as healthcare providers, logistics drivers, and emergency responders.

The Biological Reality of Early Morning Shifts

Shift work disorder is a circadian rhythm sleep-wake disorder characterized by a misalignment between an individual’s internal biological clock and the requirements of their environment or schedule. For those starting work in the early morning, the biological challenge is profound. Human physiology is governed by the suprachiasmatic nucleus (SCN) in the brain, which regulates the release of hormones like melatonin and cortisol based on light exposure.

When a worker wakes at 3:00 a.m., they are interrupting their sleep during the "biological night," a period when the body’s core temperature is at its lowest and the drive for sleep is at its physiological peak. "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," noted first author Kirsi-Marja Zitting, PhD, an investigator with the Division of Sleep and Circadian Medicine at Mass General Brigham. This misalignment creates a "double burden": the worker must fight intense biological pressure to sleep while on the job, yet they often struggle to achieve restorative sleep later in the day because their internal clock signals that it is time to be awake.

The study highlights that many early morning workers do not even identify as "shift workers." They often view their schedules as simply an early start to a normal day. However, the physiological impact is identical to that of overnight shifts, leading to chronic sleep deprivation and the severe cognitive impairments associated with SWD.

Methodology and Findings of the Solriamfetol Trial

The clinical trial was a randomized, double-blind, placebo-controlled study involving 78 participants diagnosed with shift work disorder. These participants were otherwise healthy adults whose work schedules consistently began in the early morning hours. Over a four-week period, half of the group was administered solriamfetol on workdays, while the other half received a placebo.

To measure the drug’s efficacy, researchers utilized the Maintenance of Wakefulness Test (MWT), a gold-standard objective assessment that measures an individual’s ability to remain awake in a dark, quiet, and low-stimulation environment. This test was conducted during hours that mirrored the participants’ actual work shifts. Additionally, researchers used the Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C) scales to gather subjective data on how the participants felt and functioned in their daily lives.

The results after four weeks were definitive. Participants taking solriamfetol showed a statistically significant improvement in their ability to remain awake compared to the placebo group. On average, those treated with the medication could stay alert for longer durations during the simulated work shift. Beyond the objective laboratory tests, both the participants and the supervising clinicians reported marked improvements in overall functioning. Workers noted that they were better able to manage complex tasks, felt more present during their shifts, and experienced a reduction in the "brain fog" that typically plagues those with SWD.

Comparative Advantages Over Existing Treatments

Prior to this study, medications like modafinil and armodafinil were the primary pharmacological options for treating wakefulness issues in shift workers. However, these drugs were primarily validated in populations working traditional overnight shifts (e.g., 11:00 p.m. to 7:00 a.m.). A significant drawback of some existing stimulants is their potential to interfere with subsequent sleep. For an early morning worker who finishes their shift at noon and needs to nap or sleep early in the evening to prepare for the next 3:00 a.m. start, a drug with a lingering stimulatory effect can exacerbate the cycle of insomnia.

Solriamfetol is a dual norepinephrine and dopamine reuptake inhibitor (DNRI). It was FDA-approved in 2019 for the treatment of excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea. One of its primary advantages, as observed in this trial, is its ability to promote sustained wakefulness throughout an eight-hour shift without significantly compromising the ability to fall asleep later in the day. This balance is crucial for maintaining a sustainable circadian rhythm in the long term.

The High Cost of Occupational Fatigue

The implications of this trial extend far beyond the laboratory. Shift work disorder is not merely a matter of feeling tired; it is a significant public health and safety concern. Data from the National Highway Traffic Safety Administration (NHTSA) suggests that drowsy driving is a factor in approximately 100,000 police-reported crashes annually, many of which involve workers commuting to or from early shifts.

In the workplace, the lack of concentration and reduced reaction times caused by SWD are linked to an increased frequency of industrial accidents, needle-stick injuries in hospitals, and errors in high-stakes environments like air traffic control or power plant management. Furthermore, chronic circadian disruption is associated with long-term health risks, including cardiovascular disease, metabolic syndrome, and certain types of cancer.

"The improvement we saw is clinically meaningful," said senior author Charles A. Czeisler, PhD, MD, chief of the Division of Sleep and Circadian Medicine at Mass General Brigham. "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. Shift workers are essential to how our society functions, yet they often pay a hidden biological cost."

Industry Context and Future Research Directions

The study was funded by Jazz Pharmaceuticals and Axsome Therapeutics, the latter of which currently holds the rights to Sunosi. The involvement of these pharmaceutical entities reflects a growing interest in the "wakefulness" market, as modern economies move toward 24/7 operations. However, the researchers emphasize that medication is only one part of the solution. Proper sleep hygiene, light therapy, and strategic napping remain essential components of managing SWD.

Despite the positive results, the researchers noted several limitations. The trial lasted only four weeks, leaving questions about the long-term efficacy and potential side effects of daily solriamfetol use in this specific population. Furthermore, the study cohort consisted of generally healthy adults, meaning the results might differ for individuals with underlying health conditions or those taking multiple medications.

To build on these findings, the Mass General Brigham team is currently enrolling participants for a follow-up clinical trial. This next phase will focus on the efficacy of solriamfetol in overnight shift workers, with the goal of securing broader regulatory approval for the treatment of shift work disorder across all non-traditional schedules.

Conclusion: Supporting the "Invisible" Workforce

The "early bird" shift is a cornerstone of the modern economy, yet the people who fill these roles—the bakers, the morning news anchors, the transit operators, and the warehouse pickers—have long been ignored by clinical research. By demonstrating that solriamfetol can effectively mitigate the debilitating sleepiness associated with these hours, this study paves the way for a new standard of care.

As society continues to demand round-the-clock services, the burden on the human biological clock will only increase. Research like that conducted by Czeisler, Zitting, and their colleagues serves as a vital reminder that "working hard" should not have to mean working in a state of permanent cognitive impairment. The validation of solriamfetol for early morning shift workers represents a significant step toward reconciling the demands of the modern economy with the immutable realities of human biology.