Johny Marice
Far more people work very early morning shifts than overnight schedules, yet many struggle with severe fatigue linked to shift work disorder. This condition can interfere with concentration, job performance, and safety. A new clinical trial led by researchers at Mass General Brigham found that the wake-promoting drug solriamfetol (Sunosi) helped early morning shift workers stay more alert. The findings were published in NEJM Evidence.
Addressing a Critical Gap in Shift Work Disorder Treatment
"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."
The groundbreaking research highlights a significant unmet need in occupational health. While shift work disorder has long been recognized as a debilitating condition, clinical interventions have historically focused on individuals working overnight. This new study, however, shifts the focus to the substantial population of early morning shift workers, a group often overlooked despite their significant numbers and the unique challenges they face.
Understanding the Biological Clock Disruption in Early Risers
Approximately one in four workers in the United States operates outside the traditional 9-to-5 workday, a statistic that encompasses a vast array of professions from healthcare and manufacturing to transportation and retail. Within this broad category, those who begin their shifts between 3 a.m. and 7 a.m. represent a particularly vulnerable segment. These individuals often do not identify as "shift workers" in the conventional sense, viewing their early start times as simply an accommodation for personal or family needs rather than a direct disruption of their natural circadian rhythm.
However, the biological reality is that these early start times directly conflict with the body’s innate sleep-wake cycle. "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," explained first author Kirsi-Marja Zitting, PhD, an investigator with the Division of Sleep and Circadian Medicine at Mass General Brigham. "That makes staying alert extraordinarily difficult, even when they are highly motivated." This biological imperative to sleep during these pre-dawn and early morning hours can lead to a "double burden": persistent daytime sleepiness during work hours and fragmented, insufficient sleep when attempting to rest.
The Science Behind Early Morning Fatigue
The human body’s internal clock, or circadian rhythm, is a complex system that regulates various physiological processes, including sleep-wake cycles, hormone release, and body temperature. This rhythm is primarily influenced by light exposure. For early morning shift workers, the alarm clock often sounds before sufficient natural light has signaled the brain to transition from sleep to wakefulness. This misalignment can lead to a state of chronic sleep deprivation and impaired alertness.
Data from the Bureau of Labor Statistics indicates that industries requiring early morning shifts, such as food service, healthcare support, and manufacturing, employ millions of Americans. For instance, in 2022, over 3.5 million individuals were employed in food preparation and serving occupations, many of whom work early morning or late-night shifts. Similarly, the healthcare sector, with its 24/7 operational demands, relies heavily on early morning staff to provide critical patient care. The cumulative effect of these early starts, particularly when coupled with insufficient recovery sleep, contributes to a widespread public health concern.
Health and Safety Ramifications of Shift Work Disorder
The consequences of shift work disorder extend far beyond mere tiredness. The persistent, excessive sleepiness experienced by affected individuals can have profound impacts on their cognitive function, leading to a reduction in mental sharpness, impaired judgment, and a diminished capacity for complex problem-solving. This cognitive decline directly translates to decreased productivity and an increased likelihood of errors in the workplace.
The risks are particularly acute in safety-sensitive professions. Studies have consistently linked shift work disorder to a higher incidence of motor vehicle accidents, both during commutes and on the job. For example, research published in the Journal of Occupational and Environmental Medicine has indicated that shift workers are at a significantly elevated risk of accidents compared to their daytime counterparts. Furthermore, workplace injuries are more common among individuals struggling with sleepiness and reduced alertness, posing a threat not only to the affected workers but also to their colleagues and the public.
Existing Treatments and Their Limitations
While medications like modafinil have been employed to promote wakefulness in individuals with shift work disorder, their efficacy and safety profiles have primarily been established through studies on overnight shift workers. A significant concern with these medications is their potential to interfere with sleep later in the day or night, creating a paradoxical effect that can exacerbate sleep problems for some individuals. This underscores the need for targeted therapeutic options that address the specific challenges faced by early morning shift workers.
Solriamfetol: A New Hope for Early Morning Shift Workers
Solriamfetol, the drug evaluated in this pivotal clinical trial, represents a promising therapeutic avenue. Already approved for the treatment of excessive sleepiness associated with narcolepsy and obstructive sleep apnea, solriamfetol works by increasing levels of wake-promoting neurotransmitters in the brain, namely dopamine and norepinephrine. Its pharmacological profile is particularly attractive for shift workers as it is designed to promote alertness for extended periods without significantly disrupting the ability to sleep when desired. This characteristic is crucial for individuals who need to maintain wakefulness during their early morning shifts and then transition to restorative sleep later in the day.
The Clinical Trial: Design and Methodology
The Phase 3 clinical trial, conducted by Mass General Brigham researchers, enrolled 78 participants who had been diagnosed with shift work disorder and who worked early morning shifts. The study employed a rigorous randomized, double-blind, placebo-controlled design, considered the gold standard for evaluating the efficacy of new treatments. Participants were randomly assigned to receive either solriamfetol or a placebo on their workdays for a duration of four weeks.
To objectively assess the drug’s impact on alertness, researchers utilized a controlled, low-stimulation laboratory setting designed to mimic the hours of a typical early morning shift. During these simulated work periods, participants’ ability to remain awake was meticulously monitored. In addition to these objective measures, participants also provided subjective reports on their daily functioning, including levels of sleepiness, energy, and overall quality of life. Regular consultations with clinicians allowed for ongoing assessment of their well-being and any potential adverse effects.
Promising Results: Improved Alertness and Performance
The findings from the four-week trial demonstrated a statistically significant and clinically meaningful improvement in the participants who received solriamfetol. Those taking the drug reported feeling less sleepy and were demonstrably able to remain awake for longer durations during the simulated work hours compared to the placebo group. This enhanced wakefulness translated into tangible benefits in daily life.
Both participants and their treating clinicians observed improvements in overall functioning. Participants reported a greater ability to manage their daily tasks, indicating a positive impact on their cognitive and physical capabilities. Work performance was also noted to be better, suggesting that the drug’s wake-promoting effects extended beyond the laboratory setting and into their actual work environments.
"The improvement we saw is clinically meaningful," Dr. Czeisler emphasized. "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." He further articulated the societal debt owed to these essential workers: "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."
Future Directions and Broader Implications
While the results of this trial are highly encouraging, the researchers are quick to point out that further investigation is warranted. The current study focused on otherwise healthy adults and had a relatively short duration of four weeks. Understanding the long-term effects of solriamfetol in early morning shift workers will be crucial for establishing its sustained efficacy and safety profile.
The research team is already moving forward with a follow-up clinical trial that will investigate solriamfetol in overnight shift workers. This expansion of research could potentially lead to broader approval for the drug’s use in treating shift work disorder across all types of non-traditional schedules.
The implications of this research are far-reaching. By offering a targeted treatment for a common and debilitating condition, solriamfetol has the potential to significantly improve the health, safety, and well-being of millions of early morning shift workers. This could lead to reduced workplace accidents, increased productivity, and a better quality of life for individuals whose contributions are vital to the functioning of modern society. The study represents a significant step forward in acknowledging and addressing the unique health challenges faced by this often-overlooked segment of the workforce.
The study was funded by Jazz Pharmaceuticals, Axsome Therapeutics, and Brigham and Women’s Hospital Center for Clinical Investigation. The clinical trial registration number is NCT04788953.
Mass General Brigham Authors:
- Kirsi-Marja Zitting, PhD
- Charles A. Czeisler, PhD, MD
- Katherine R. Gilmore
- Brandon J. Lockyer
- Wei Wang
- Nicolas C. Issa
- Stuart F. Quan
- Jonathan S. Williams
- Jeanne F. Duffy
Additional Author:
- Eileen B. Leary
