Solriamfetol Shows Significant Promise in Treating Shift Work Disorder Among Early Morning Workers in New Clinical Trial

A groundbreaking clinical trial led by researchers at Mass General Brigham has demonstrated that solriamfetol, a wake-promoting medication, significantly improves alertness and functional performance in individuals working early morning shifts. The study, published in NEJM Evidence, represents the first clinical trial specifically targeting the "early bird" demographic of shift workers—those who begin their duties between 3:00 a.m. and 7:00 a.m. While overnight workers have traditionally been the focus of sleep deprivation research, this new data highlights a critical and often overlooked segment of the labor force that suffers from profound biological misalignment and its attendant safety risks.

Shift Work Disorder (SWD) is a chronic condition characterized by excessive sleepiness, insomnia, or both, resulting from a work schedule that overlaps with the typical sleep period. For early morning workers, the challenge is twofold: they must perform high-stakes tasks during the biological "circadian trough"—the period when the body’s internal clock is most insistently signaling for sleep—and they often struggle to obtain restorative sleep during the daylight hours when the rest of society is active. The Mass General Brigham study suggests that solriamfetol, currently marketed under the brand name Sunosi, could provide a vital therapeutic intervention for this population.

The Biological Reality of the Early Morning Shift

The human body is governed by a circadian rhythm, an internal 24-hour clock regulated by the suprachiasmatic nucleus in the brain. This rhythm dictates cycles of alertness and sleepiness by managing the release of hormones like melatonin and cortisol. For the approximately 25% of the global workforce that operates outside of a standard 9-to-5 schedule, this internal clock is frequently at odds with external demands.

Individuals starting work in the pre-dawn hours are often required to wake up during their biological night. According to Dr. Kirsi-Marja Zitting, an investigator with the Division of Sleep and Circadian Medicine at Mass General Brigham and the study’s first author, this timing is particularly treacherous. "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," Zitting explained. "That makes staying alert extraordinarily difficult, even when they are highly motivated."

The study notes that many of these workers do not even identify as "shift workers," viewing their schedules as merely an early start to a normal day. However, the physiological impact is identical to that of traditional overnight shifts, leading to "double burdens" of excessive sleepiness during work and fragmented sleep during time off.

Clinical Trial Design and Methodology

To address the lack of data regarding this specific demographic, the research team conducted a four-week, randomized, double-blind, placebo-controlled trial. The study enrolled 78 participants who were diagnosed with Shift Work Disorder and were consistently working early morning shifts.

Participants were randomly assigned to receive either solriamfetol or a placebo on their scheduled workdays. The efficacy of the drug was measured using several standardized clinical metrics:

1. Maintenance of Wakefulness Test (MWT): Conducted in a controlled, low-stimulation laboratory environment, this test measures a person’s ability to remain awake during hours that correspond to their work shift.
2. Clinical Global Impression of Change (CGI-C): A scale used by clinicians to assess whether a patient’s overall condition has improved or worsened relative to a baseline state.
3. Patient Global Impression of Change (PGI-C): A self-reported metric where participants rate their own perception of improvement in daily functioning and alertness.
4. Work Performance Scales: Assessments focused on the ability to concentrate, manage tasks, and maintain productivity throughout an eight-hour period.

Solriamfetol differs from older stimulants because it is a dual dopamine and norepinephrine reuptake inhibitor (DNRI). Unlike some medications that have a short half-life or cause a "crash," solriamfetol is designed to provide sustained wakefulness throughout a shift without necessarily preventing the user from falling asleep later in the day, a common side effect of traditional stimulants like caffeine or certain amphetamines.

Key Findings: Improved Alertness and Safety

The results of the trial were definitive. After four weeks of treatment, the group receiving solriamfetol showed statistically significant improvements compared to the placebo group. Participants on the medication were able to remain awake longer during the MWT and reported feeling substantially more alert during their actual work hours.

The clinical implications of these findings are substantial. Senior author Dr. Charles A. Czeisler, chief of the Division of Sleep and Circadian Medicine at Mass General Brigham, emphasized that the improvements were not just statistically significant but "clinically meaningful."

"These workers were able to stay awake and alert throughout a full eight-hour shift," Czeisler stated. "This has real implications for performance, safety, and quality of life."

In terms of safety, the data suggests a potential reduction in "micro-sleeps"—brief, involuntary moments of sleep that can last from a fraction of a second to thirty seconds. For early morning workers in sectors such as transportation, healthcare, and heavy machinery operation, micro-sleeps are a primary cause of catastrophic accidents. By stabilizing wakefulness, solriamfetol may mitigate the risks of "drowsy driving" and workplace injuries, which are disproportionately high among SWD sufferers.

The Economic and Societal Burden of Sleep Deprivation

The societal cost of Shift Work Disorder is immense, though often hidden. According to data from the National Safety Council, tired workers cost U.S. employers approximately $136 billion annually in lost productivity. Furthermore, shift workers are statistically more likely to suffer from long-term health issues, including cardiovascular disease, metabolic syndrome, and mental health disorders such as depression and anxiety, all of which are exacerbated by chronic sleep-wake misalignment.

Early morning shifts are essential to the modern economy. They include the nurses and doctors handing over shifts at hospitals, the logistics drivers ensuring goods reach stores before opening, the pilots of early-bird flights, and the utility workers maintaining infrastructure. Despite their essential nature, these workers have historically been excluded from clinical trials for wake-promoting agents, which have prioritized night-shift workers or those with narcolepsy.

This study begins to bridge that gap. By validating a treatment for the 3:00 a.m. to 7:00 a.m. cohort, the research acknowledges the specific biological strain placed on these individuals. The findings suggest that targeted pharmacological intervention can help bridge the gap between biological necessity and economic demand.

Comparative Analysis: Solriamfetol vs. Modafinil

Prior to this study, modafinil and armodafinil were the primary medications studied and prescribed for Shift Work Disorder. While effective for many, these drugs have limitations. Some patients find that modafinil stays in their system too long, making it difficult to achieve restorative sleep once their shift ends.

Solriamfetol, which was FDA-approved in 2019 for the treatment of excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea, appears to offer a more favorable profile for certain users. In this trial, researchers noted that solriamfetol promoted alertness for the duration of the work shift without the significant sleep-interference issues that can plague other treatments. However, the researchers cautioned that further comparative studies are needed to determine which patient profiles benefit most from each specific medication.

Chronology of the Research and Future Directions

The trial (NCT04788953) began recruitment in early 2021, focusing on healthy adults who met the diagnostic criteria for SWD and worked at least three early morning shifts per week. Following the successful four-week pilot, the research team has moved toward broader investigations.

Current and future phases of this research include:

• Long-term Safety Monitoring: Because the published trial lasted only four weeks, researchers are looking to gather data on the effects of solriamfetol use over six months to a year.
• Overnight Shift Study: Mass General Brigham is currently enrolling participants for a follow-up trial to evaluate solriamfetol’s efficacy specifically for overnight workers (11:00 p.m. to 7:00 a.m.).
• Impact on Metabolic Health: Future studies may investigate whether improved wakefulness and better-regulated sleep-wake cycles can mitigate the metabolic damage (such as insulin resistance) often seen in shift workers.

Official Responses and Funding

The study was funded through a combination of support from Jazz Pharmaceuticals, Axsome Therapeutics (the current manufacturer of Sunosi), and the Brigham and Women’s Hospital Center for Clinical Investigation. While the involvement of pharmaceutical companies is standard for late-stage clinical trials, the researchers maintained rigorous independent oversight of the data collection and analysis.

Industry analysts suggest that if solriamfetol receives expanded FDA approval for Shift Work Disorder based on these and upcoming trials, it could become a standard of care in occupational medicine. Occupational health experts have reacted positively to the study, noting that providing workers with tools to manage their biological clocks is a matter of both employee welfare and public safety.

Conclusion: A New Standard for Occupational Health

The Mass General Brigham study serves as a wake-up call for the medical community and employers alike. It highlights the fact that "early morning" is not just a time of day, but a specific biological challenge that requires dedicated scientific attention.

As society continues to move toward a 24-hour operational model, the prevalence of Shift Work Disorder is expected to rise. The success of solriamfetol in this clinical trial offers a glimmer of hope for millions of workers who currently struggle to stay awake during their shifts and sleep during their off-hours. By treating the symptoms of SWD, researchers are not just improving job performance; they are potentially saving lives by reducing the incidence of fatigue-related accidents on our roads and in our workplaces.

"Shift workers are essential to how our society functions," Dr. Czeisler concluded. "Yet they often pay a hidden biological cost. This study shows we can do better for them." With the publication of these results in NEJM Evidence, the medical community takes a significant step toward recognizing and mitigating the physiological toll of the early morning shift.