Solriamfetol Shows Promise in Improving Alertness for Early Morning Shift Workers Facing Shift Work Disorder

The landscape of modern labor is increasingly defined by non-traditional hours, with approximately 20% to 25% of the global workforce operating outside the conventional 9-to-5 window. Among these individuals, those who begin their duties in the very early hours of the morning—typically between 3:00 a.m. and 7:00 a.m.—represent a significant but often overlooked demographic. While overnight shift workers have long been the focus of occupational health studies, a new clinical trial led by researchers at Mass General Brigham suggests that early morning workers face equally grueling biological challenges. The study, recently published in NEJM Evidence, reveals that the wake-promoting medication solriamfetol, marketed under the name Sunosi, significantly improves alertness and reduces the "hidden biological cost" paid by those who work while the rest of the world sleeps.

The Silent Crisis of the Early Morning Shift

Shift Work Disorder (SWD) is a circadian rhythm sleep disorder characterized by excessive sleepiness during work hours and insomnia when the individual attempts to sleep. For many, the term "shift work" evokes images of the midnight oil—factory workers on the graveyard shift or emergency room nurses working through the night. However, the researchers at Mass General Brigham point out that the largest segment of the non-traditional workforce actually consists of early morning starters.

These individuals include delivery drivers, logistics coordinators, transit operators, healthcare professionals, and retail workers who prepare storefronts before dawn. Because these workers often finish their days in the early afternoon, they—and society at large—frequently fail to categorize their schedule as "shift work." Instead, it is viewed as a disciplined, early start. Yet, from a physiological perspective, waking up at 2:00 a.m. or 3:00 a.m. forces the brain to function during the "circadian trough," the period when core body temperature is at its lowest and the biological drive for sleep is at its peak.

Dr. Charles A. Czeisler, chief of the Division of Sleep and Circadian Medicine at Mass General Brigham and senior author of the study, noted that this specific group has been largely ignored in clinical literature. "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," Czeisler stated. The study aims to bridge this gap, addressing the needs of workers who are biologically programmed to be asleep during their most critical working hours.

Understanding the Physiological Toll

The human body is governed by a master clock located in the suprachiasmatic nucleus of the brain. This clock regulates a 24-hour cycle of alertness and rest, primarily influenced by light exposure. When a worker wakes up at 3:00 a.m., they are defying millions of years of evolutionary biology. This misalignment leads to more than just a feeling of tiredness; it results in a state of "sleep debt" and "circadian misalignment" that can have catastrophic consequences.

First author Kirsi-Marja Zitting, PhD, emphasized the "double burden" these workers face. Not only must they struggle to remain vigilant during their shifts, but they also find it difficult to obtain restorative sleep during the day when the sun is up and the rest of society is active. This chronic state of exhaustion is linked to a higher incidence of workplace accidents, errors in judgment, and long-term health issues such as cardiovascular disease, metabolic syndrome, and cognitive decline.

Methodology of the Solriamfetol Trial

To address this issue, researchers conducted a double-blind, placebo-controlled clinical trial involving 78 adults diagnosed with Shift Work Disorder. All participants were regular early morning shift workers. The cohort was split into two groups: one receiving a daily dose of solriamfetol and the other receiving a placebo over a four-week period.

Solriamfetol is a dual norepinephrine and dopamine reuptake inhibitor (DNRI). Unlike traditional stimulants, which can cause jitters or a "crash" effect, solriamfetol is designed to promote sustained wakefulness. It had previously received FDA approval for treating excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, but its efficacy specifically for the early morning workforce remained unproven until now.

The researchers utilized several metrics to gauge the drug’s effectiveness:

1. Maintenance of Wakefulness Test (MWT): Participants were placed in a low-stimulation, quiet environment and asked to remain awake for as long as possible. This is the gold standard for measuring a person’s ability to resist sleep.
2. Clinical Global Impression of Change (CGI-C): Clinicians assessed the overall improvement in the participants’ condition.
3. Patient-Reported Outcomes: Workers kept logs regarding their productivity, mood, and ability to perform daily tasks.

Findings: A Significant Boost in Vigilance

The results of the trial were conclusive. After four weeks, the participants who took solriamfetol demonstrated a marked improvement in their ability to stay awake during hours that mirrored their work shifts. On average, those in the solriamfetol group could remain awake significantly longer during the MWT than those in the placebo group.

Beyond the laboratory metrics, the real-world implications were notable. Both the participants and the monitoring physicians reported enhanced daily functioning. Workers reported that they felt more capable of managing complex tasks and felt safer during their commutes—a critical factor, given that drowsy driving is a leading cause of vehicular accidents among shift workers.

"The improvement we saw is clinically meaningful," Czeisler observed. He highlighted that the medication allowed workers to maintain alertness throughout a full eight-hour shift without the significant sleep disruption later in the day that is often associated with other wake-promoting agents like modafinil.

Comparison with Existing Treatments

Historically, shift workers have turned to caffeine or medications like modafinil and armodafinil to stay awake. While effective for some, these substances have limitations. Modafinil has a relatively long half-life, which can make it difficult for a worker to fall asleep once they return home from an early shift. If a worker takes a stimulant at 4:00 a.m. to stay awake until noon, but the drug remains active in their system until 8:00 p.m., their "rest window" is effectively destroyed, worsening the cycle of exhaustion.

Solriamfetol appears to offer a more balanced profile for this specific use case. By targeting dopamine and norepinephrine reuptake, it supports the brain’s natural alertness mechanisms. The trial suggested that solriamfetol provided the necessary "up-time" without severely penalizing the worker’s ability to recover during their scheduled sleep periods.

Economic and Safety Implications

The societal cost of Shift Work Disorder is staggering. Data from the National Safety Council suggests that fatigue-related productivity losses cost U.S. employers approximately $136 billion annually. In sectors like transportation and healthcare, the cost isn’t just financial; it is measured in human lives.

A study by the AAA Foundation for Traffic Safety found that drivers who sleep less than five hours in a 24-hour period have a crash risk comparable to someone driving drunk. For an early morning worker who wakes up at 2:30 a.m. after failing to fall asleep before 10:00 p.m. the night before, this level of impairment is a daily reality.

The Mass General Brigham study suggests that by managing the symptoms of SWD through targeted pharmacological intervention, the risks of "microsleeps"—brief, involuntary moments of sleep that can last a few seconds—are significantly reduced. This has the potential to lower the rate of workplace injuries and transit-related fatalities.

Future Research and Broader Applications

While the results of the four-week trial are promising, the research team was careful to note that further study is required. The trial consisted of otherwise healthy adults, and the long-term effects of daily solriamfetol use for shift work remain to be seen.

The research team is currently expanding their scope. A follow-up clinical trial is already underway, specifically enrolling overnight shift workers. If these subsequent trials mirror the success of the early morning study, it could pave the way for solriamfetol to receive broader regulatory approval specifically for Shift Work Disorder across all non-traditional schedules.

The study was a collaborative effort involving experts from various fields of sleep medicine, including Katherine R. Gilmore, Brandon J. Lockyer, and Jeanne F. Duffy. The research was supported by funding from Jazz Pharmaceuticals and Axsome Therapeutics, the companies involved in the development and distribution of the drug, as well as the Brigham and Women’s Hospital Center for Clinical Investigation.

Conclusion: Recognizing the Essential Workforce

As the global economy moves toward a 24-hour cycle, the reliance on early morning workers will only increase. From the baristas who serve the first cup of coffee to the warehouse workers who ensure overnight deliveries arrive on time, these individuals are the "gears" of modern society.

The findings published in NEJM Evidence represent a shift in how the medical community views these workers. By validating the severity of their struggle and providing a potential solution in solriamfetol, researchers are moving toward a future where the "biological cost" of employment is no longer an inevitable burden. As Dr. Czeisler concluded, "Shift workers are essential to how our society functions… This study shows we can do better for them."