Clinical Trial Finds Solriamfetol Effective in Reducing Excessive Sleepiness Among Early Morning Shift Workers

Researchers at Mass General Brigham have released the results of a groundbreaking clinical trial demonstrating that solriamfetol, a wake-promoting medication currently used for narcolepsy and sleep apnea, significantly improves alertness and functional performance in individuals working early morning shifts. The study, published in the journal NEJM Evidence, represents a critical advancement in occupational medicine, as it is the first clinical trial to specifically target the unique challenges faced by workers whose shifts begin in the predawn hours—a demographic that constitutes the largest segment of the non-traditional workforce yet remains largely underserved by sleep medicine research.

Shift work disorder (SWD) is a chronic condition characterized by excessive sleepiness during work hours and insomnia when attempting to sleep during the day. While much of the existing literature and pharmaceutical focus has centered on overnight or "graveyard" shift workers, this new research highlights the profound biological strain placed on those who clock in between 3:00 a.m. and 7:00 a.m. For these individuals, the requirement to be productive and alert coincides with the lowest point of the human circadian rhythm, creating a "biological mismatch" that can have devastating consequences for safety, health, and quality of life.

The Hidden Epidemic of Early Morning Fatigue

Approximately 25% of the global workforce operates on a schedule that falls outside the standard 9-to-5 window. Within this group, early morning workers represent a significant majority. These roles are foundational to modern society, spanning sectors such as healthcare, transportation, logistics, emergency services, and food production. Despite their ubiquity, many individuals in these roles do not self-identify as "shift workers." Instead, they often view their exhaustion as a personal failing or an unavoidable consequence of a "demanding morning routine."

"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 the study’s senior author, Charles A. Czeisler, PhD, MD, who serves as the chief and senior physician of the Division of Sleep and Circadian Medicine at Mass General Brigham. Dr. Czeisler emphasized that the study addresses a major gap in medical knowledge by focusing on those who start their day while the rest of the world is biologically programmed to be in deep sleep.

The biological reality of the early morning shift is unforgiving. Between the hours of 3:00 a.m. and 6:00 a.m., the human body experiences a natural dip in core temperature and a surge in melatonin, the hormone responsible for signaling sleep. Forcing the brain into a state of high-stakes alertness during this window is not merely a matter of willpower; it is a battle against millions of years of evolutionary biology. First author Kirsi-Marja Zitting, PhD, noted that these workers face a "double burden." They must fight sleepiness to perform their jobs safely and then struggle to achieve restorative sleep later in the morning when the environment is noisy and the sun is rising, further disrupting their internal clocks.

Study Methodology and the Evaluation of Solriamfetol

The clinical trial conducted by the Mass General Brigham team was a randomized, double-blind, placebo-controlled study involving 78 participants. All participants were diagnosed with shift work disorder and were regular early morning shift workers. The cohort was divided into two groups: one receiving solriamfetol (marketed under the brand name Sunosi) and the other receiving a placebo over a four-week period.

The researchers employed rigorous testing methods to measure the drug’s efficacy. Rather than relying solely on self-reported data, the team used controlled, low-stimulation environments to assess the participants’ ability to remain awake during hours that mirrored their actual work schedules. These assessments were complemented by clinician interviews and standardized scales to measure daily functioning, workplace productivity, and overall quality of life.

Solriamfetol is a dual norepinephrine and dopamine reuptake inhibitor (DNRI). Unlike traditional stimulants like amphetamines, which can cause significant "jitteriness" or a subsequent "crash," solriamfetol works by increasing the levels of wake-promoting neurotransmitters in the brain in a more sustained and controlled manner. It had already received FDA approval for treating excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, but its application for shift work disorder—specifically for the early morning demographic—was previously untested.

Analyzing the Clinical Results

The findings of the trial were conclusive. After four weeks of treatment, the group receiving solriamfetol demonstrated a marked improvement in their ability to stay awake compared to the placebo group. The data showed that participants were able to maintain alertness throughout the duration of a standard eight-hour shift, even during the most difficult predawn hours.

Beyond the objective measures of wakefulness, the subjective improvements were equally significant. Both the participants and the evaluating clinicians reported higher levels of "global functioning." This term encompasses the ability to manage complex tasks, interact socially without irritability caused by exhaustion, and maintain focus during high-risk activities like driving.

"The improvement we saw is clinically meaningful," Dr. Czeisler stated. "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."

One of the most promising aspects of the trial was the drug’s safety profile regarding subsequent sleep. A common drawback of other wake-promoting agents, such as modafinil, is their long half-life, which can interfere with a worker’s ability to fall asleep once they finally return home. The trial indicated that solriamfetol, when taken at the start of an early morning shift, provided the necessary alertness during work hours without significantly degrading the quality of the sleep that followed.

Safety and Economic Implications of Shift Work Disorder

The implications of this study extend far beyond the laboratory. Shift work disorder is not just a health issue; it is a public safety and economic crisis. Data from the National Highway Traffic Safety Administration (NHTSA) suggests that drowsy driving is responsible for thousands of fatalities and tens of thousands of injuries annually in the United States alone. For early morning workers, the commute to work often occurs during the period of peak biological sleepiness, making them particularly vulnerable to motor vehicle accidents.

In the workplace, the costs of fatigue are staggering. Sleep-deprived employees are more prone to errors in judgment, slower reaction times, and workplace injuries. In high-stakes environments such as hospitals or industrial plants, a single moment of micro-sleep—a brief, involuntary episode of sleep lasting seconds—can result in catastrophic errors. Economic analyses estimate that sleep-related productivity losses cost the U.S. economy over $400 billion per year. By providing a pharmacological tool to mitigate these risks, solriamfetol could potentially reduce the frequency of industrial accidents and improve the overall efficiency of the essential workforce.

Furthermore, the long-term health consequences of untreated shift work disorder are well-documented. Chronic sleep disruption is linked to an increased risk of cardiovascular disease, metabolic disorders such as type 2 diabetes, and mental health challenges including depression and anxiety. While solriamfetol is not a "cure" for the underlying circadian disruption, by managing the most acute symptom—excessive sleepiness—it may help workers maintain a more stable lifestyle, potentially mitigating some of the secondary health impacts of their schedules.

Future Research and the Path Toward Broader Approval

While the results of the Mass General Brigham study are promising, the researchers urge a cautious interpretation regarding long-term use. The trial lasted only four weeks and focused on a relatively healthy group of adults. As with any medication that affects the central nervous system, understanding the effects of multi-year use is essential.

The team is already moving forward with the next phase of research. They are currently enrolling participants for a follow-up clinical trial that will focus specifically on overnight shift workers. The goal is to build a comprehensive body of evidence that could support broader regulatory approval for solriamfetol as a primary treatment for all forms of shift work disorder.

"Shift workers are essential to how our society functions, yet they often pay a hidden biological cost," Dr. Czeisler remarked. "This study shows we can do better for them."

The funding for this research was provided by Jazz Pharmaceuticals and Axsome Therapeutics, alongside the Brigham and Women’s Hospital Center for Clinical Investigation. As the medical community continues to grapple with the realities of a 24-hour society, this study serves as a vital reminder that the "early birds" of the workforce deserve the same level of scientific attention and clinical care as those on more traditional schedules. The successful application of solriamfetol in this context marks a significant step toward reclaiming the safety and well-being of millions of essential workers worldwide.