Far more people work early shifts than night shifts, yet many suffer from severe fatigue associated with shift work disorder. This condition can impair concentration, work performance, and safety. A new clinical study led by researchers at Mass General Brigham found that the wake-promoting drug solriamfetol (Sunosi) helped early-shift workers stay more alert. The results were published in NEJM Evidence.

“Until now, no clinical trial had tested a treatment for shift work disorder in early-shift workers, even though this is the most common type of shift schedule,” said lead author Charles A. Czeisler, PhD, MD, director and senior physician in the Department of Sleep and Circadian Medicine at Mass General Brigham’s medical school. “This study fills a major gap by focusing on workers who start their day when most people are still asleep.”

Why Early Shifts Disrupt the Body’s Internal Clock

About one in four workers works outside the typical 9-to-5 schedule, including those who start work very early in the morning. Many people with such schedules do not consider themselves shift workers, but simply view their daily routine as starting the day earlier than usual. Nevertheless, they are at high risk for shift work disorder, which is associated with disrupted sleep patterns and persistent daytime sleepiness.

“People who start work between 3 and 7 a.m. wake up at a time when the brain is biologically programmed for sleep. This makes it extremely difficult to stay alert, even if they are highly motivated,” said lead author Kirsi-Marja Zitting, PhD, a researcher in the Division of Sleep and Circadian Medicine at the Mass General Brigham Department of Medicine. “They often struggle with a double burden—excessive sleepiness during work hours and difficulty getting enough sleep when they have the opportunity to rest.”

Health and Safety Risks of Shift Work Disorder

Shift work disorder is far more than just a temporary feeling of fatigue after a night shift – it represents a chronic strain on the entire body and can have profound effects on cognitive performance, safety, and long-term health. At its core, it arises from the persistent discrepancy between work hours and the natural circadian rhythm—that is, the human biological day-night cycle. Since this rhythm is evolutionarily designed for sleeping at night and being active during the day, the reversal or constant shifting of these times leads to a permanent internal desynchronization.

One of the most immediate consequences is reduced mental performance. Those affected often report difficulty concentrating, slowed thinking, and problems making decisions. Neurobiologically, this can be explained by the fact that sleep deprivation and circadian misalignment impair activity in the prefrontal cortex—that is, the area of the brain responsible for planning, attention, and problem-solving. At the same time, reaction speed decreases and the likelihood of errors increases. These effects are not only noticeable in the short term but can intensify under chronic stress and lead to a permanent decline in performance. Closely linked to this is reduced productivity. When attention, memory, and cognitive flexibility are impaired, work performance inevitably declines as well. Tasks take longer, require more frequent corrections, or are left incomplete. This can have significant consequences, particularly in professions that require high precision—such as healthcare, industry, or the transportation sector. Furthermore, many affected individuals are less motivated and show lower commitment due to constant fatigue, which further impairs productivity.

A particularly critical aspect is the increased risk of accidents, both on the road and in the workplace. Fatigue affects the brain in many ways similar to alcohol: reaction times are prolonged, attention wanes, and the ability to assess risks correctly is impaired. Studies show that people have a significantly increased risk of car accidents after a night shift, especially on the way home when natural fatigue peaks. So-called “micro-sleep” episodes, in which the brain falls into a sleep-like state for a few seconds, can also occur—often without the person being aware of it. These brief lapses are particularly dangerous in traffic or when operating machinery. The risk of workplace accidents also increases significantly. In industries involving physical labor or complex technical processes, even a minor lapse in attention can have serious consequences. Research shows that accidents occur more frequently in the early morning hours—precisely when the body is biologically primed for sleep. In addition, chronic fatigue and stress can impair compliance with safety regulations because those affected tend to take shortcuts or work less carefully.

In the long term, these problems often reinforce each other. Sleep deprivation leads to cognitive impairments, which increase the risk of accidents, and repeated stress can lead to chronic stress. This stress, in turn, negatively affects sleep, creating a vicious cycle. Emotional and psychological factors can also come into play: irritability, reduced stress tolerance, and even depressive symptoms are more common among shift workers, which can further impair performance and safety.

Wakefulness-Promoting Medication

Medications such as modafinil are sometimes used to promote wakefulness, but these agents have so far been studied mainly in night workers and can impair sleep later in the day. Solriamfetol, the medication examined in this study, is already approved for the treatment of excessive daytime sleepiness in people with obstructive sleep apnea and narcolepsy. The researchers considered it a promising option because it can promote alertness over extended periods without significantly disrupting sleep later on.

Pharmacologically, solriamfetol belongs to the class of drugs known as dopamine and norepinephrine reuptake inhibitors (DNRI). This means that it increases the concentration of the neurotransmitters dopamine and norepinephrine in the brain by blocking their reuptake into nerve cells. These two neurotransmitters are crucial for wakefulness, attention, and motivation. Through this mechanism, the drug specifically enhances wakefulness without causing the classic “high” associated with amphetamines.

An important difference from older active ingredients like modafinil is that solriamfetol has a more direct and predictable effect on these neurotransmitter systems. While modafinil acts in a more complex manner and influences multiple systems, solriamfetol has a pharmacologically “clearer” focus. This results in the wake-promoting effect often being stronger and more consistent throughout the day. Another advantage observed in studies is that solriamfetol improves alertness without impairing subsequent sleep as much as some other stimulants. This is particularly important for conditions such as shift work disorder, where the goal is not only alertness during work but also as restful a sleep as possible afterward.

Clinical Study Shows Improved Alertness and Performance

The study involved 78 early-shift workers who had been diagnosed with shift work disorder. Participants were randomly assigned and received either solriamfetol or a placebo on workdays over a four-week period. Researchers assessed their ability to stay awake in a controlled, low-stimulus environment during hours corresponding to their typical work schedule. Participants also reported on their daily functioning and met regularly with doctors.

After four weeks, those who received solriamfetol showed significant improvements. They were less sleepy and were able to stay awake longer during simulated work hours. Both the participants and their doctors noted better overall functioning, improved work performance, and a greater ability to manage daily tasks. “The observed improvement is clinically significant. These workers were able to remain awake and alert throughout an entire eight-hour shift, which has real-world implications for performance, safety, and quality of life,” said Czeisler. “shift workers are essential to the functioning of our society, yet they often pay a hidden biological price. This study shows that we can do more for them.”

The researchers emphasized that early-shift workers have been little studied to date and that the current study lasted only four weeks and included otherwise healthy adults. Further research is needed to understand the long-term effects of the treatment. The team is currently recruiting participants for a follow-up clinical trial to study solriamfetol in night shift workers, which could help secure broader approval for the treatment of shift work disorder.