New Clinical Trial Finds Wake-Promoting Drug Solriamfetol Significantly Improves Alertness in Early Morning Shift Workers

The modern global economy runs continuously, supported by millions of individuals who operate outside the traditional Monday-through-Friday, nine-to-five framework. While much of the public discourse surrounding non-standard work schedules focuses on overnight shifts, statistics indicate that a far greater proportion of the workforce is employed during the early morning hours. Despite its prevalence, this schedule type has historically been overlooked in clinical research regarding sleep disorders. However, a landmark clinical trial led by researchers at Mass General Brigham has successfully evaluated a therapeutic intervention tailored specifically to early morning shift workers, offering new hope for millions struggling with chronic, debilitating fatigue.

The study, published in the peer-reviewed journal NEJM Evidence, investigated the efficacy of the wake-promoting medication solriamfetol, commercially known as Sunosi, in mitigating the severe daytime sleepiness associated with shift work disorder (SWD). By focusing on individuals who begin their days in the dead of night or the early hours of dawn, the research addresses a critical gap in occupational medicine and clinical sleep science, providing actionable insights into how employers and healthcare providers can better support an essential segment of the labor force.

Understanding the Hidden Burden of Early Morning Shifts

To appreciate the significance of the Mass General Brigham trial, one must first examine the physiological realities of human circadian rhythms. Approximately one in four workers in industrialized nations is employed outside standard daylight hours. Within this demographic, a substantial percentage starts work between 3:00 a.m. and 7:00 a.m.

Crucially, many individuals working these early schedules do not self-identify as traditional "shift workers." Instead, they view their routines merely as waking up earlier than average to commute to jobs in healthcare, transportation, sanitation, manufacturing, and emergency services. Consequently, they often fail to recognize that their symptoms stem from a recognized clinical condition.

Shift work disorder is characterized by insomnia during intended periods of rest and excessive sleepiness during waking hours, driven by a misalignment between an individual’s work schedule and their internal biological clock. For those starting work in the early pre-dawn hours, the physiological challenge is profound.

During these hours, the human brain is biologically programmed to produce melatonin and promote deep sleep. Forcing the body into a state of high cognitive alertness against this biological tide creates what sleep researchers term a "double burden." Affected workers must contend with intense drowsiness while trying to perform complex tasks, coupled with an inability to achieve restorative sleep when they finally return home.

Prior to this study, therapeutic options for SWD—such as modafinil—were studied almost exclusively in overnight workers. These existing treatments frequently carried drawbacks, including the potential to disrupt subsequent sleep cycles. Furthermore, no clinical trials had ever rigorously tested a pharmacologic intervention for workers on early morning schedules, despite this demographic representing the largest segment of non-standard shift workers.

Methodological Rigor and Clinical Trial Design

To address this knowledge gap, the research team designed a rigorous, randomized, double-blind, placebo-controlled clinical trial. The study enrolled 78 participants, all of whom were early morning shift workers formally diagnosed with shift work disorder.

Over a four-week trial period, participants were randomly assigned to receive either daily doses of solriamfetol or a matching placebo on their workdays. Solriamfetol is a dual-acting dopamine and norepinephrine reuptake inhibitor that has previously received regulatory approval to treat excessive daytime sleepiness in patients suffering from obstructive sleep apnea and narcolepsy. Researchers identified the drug as an ideal candidate for evaluation because of its pharmacological profile, which promotes sustained alertness over extended periods without causing the erratic sleep disruptions associated with older wake-promoting agents.

The trial utilized a combination of objective testing and subjective reporting to evaluate outcomes. Investigators assessed participants’ physiological ability to remain awake in a controlled, low-stimulation environment during hours that mirrored their actual work shifts. In addition, participants maintained detailed logs and met regularly with clinical staff to report on their daily functioning, cognitive performance, and subjective experiences of fatigue.

Key Findings and Performance Metrics

The results of the four-week trial demonstrated clear, statistically significant benefits for the cohort receiving solriamfetol compared to the placebo group. Participants treated with the medication exhibited a markedly enhanced ability to resist sleep during simulated work hours and reported substantial reductions in daytime drowsiness.

Furthermore, these physiological improvements translated directly into functional gains in daily life. Both the participants and their supervising clinicians noted enhancements in overall functional capacity, improved workplace performance, and a heightened capability to manage routine domestic and professional responsibilities.

According to senior author Dr. Charles A. Czeisler, chief and senior physician of the Division of Sleep and Circadian Medicine in the Mass General Brigham Department of Medicine, the observed improvements carry profound real-world consequences. The data confirmed that workers could maintain alertness and concentration throughout a complete eight-hour shift, directly mitigating the cognitive deficits that typically compromise safety and productivity during pre-dawn hours.

Broader Implications for Public Health and Workplace Safety

The implications of the Mass General Brigham study extend far beyond individual comfort, touching upon core issues of public safety, occupational health, and economic productivity. Shift work disorder is widely associated with an elevated risk of adverse health outcomes, including cardiovascular disease, metabolic dysfunction, and mental health challenges such as depression and anxiety.

On a day-to-day basis, the cognitive impairments linked to unmanaged SWD present immediate dangers. Reduced mental sharpness and delayed reaction times significantly increase the probability of motor vehicle accidents during commutes, as well as critical errors and traumatic injuries in workplace environments. Because early morning workers are often responsible for critical infrastructure—including healthcare delivery, public transit, and freight logistics—the societal cost of unmanaged fatigue is immense.

Experts note that while lifestyle modifications, strategic napping, and light therapy remain foundational components of managing circadian misalignment, pharmacological tools like solriamfetol offer an essential intervention for individuals whose occupational demands make purely behavioral adjustments insufficient. By establishing the safety and efficacy of solriamfetol in this specific population, the trial provides clinicians with a validated tool to help patients regain control over their alertness and overall quality of life.

Limitations and Future Research Directions

Despite the positive outcomes, the research team emphasized that the study has specific limitations that must be addressed in future investigations. The trial was relatively short in duration, lasting only four weeks, and focused exclusively on an otherwise healthy adult population. Consequently, additional research is required to evaluate the long-term safety, efficacy, and tolerability of continuous solriamfetol use over extended periods.

Building upon the success of this initial trial, the investigative team has already initiated next steps. Researchers are currently enrolling participants for a follow-up clinical trial designed to study solriamfetol in overnight shift workers. Data from this expanded research effort are expected to provide a comprehensive dataset that could support broader regulatory approvals for treating shift work disorder across all schedules.

The study was supported by research funding from Jazz Pharmaceuticals and Axsome Therapeutics, alongside institutional support from the Brigham and Women’s Hospital Center for Clinical Investigation. The trial is officially registered under ClinicalTrials.gov identifier NCT04788953.

As society continues to demand round-the-clock services, the physiological toll paid by the labor force cannot be ignored. The findings from Mass General Brigham mark a critical step forward, demonstrating that targeted medical science can successfully alleviate the hidden costs borne by millions of early morning workers.