Burnout, characterized by emotional exhaustion as well as feeling cynical, ineffective or unaccomplished at work, is bad for both employees and employers.

For doctors and hospitals, though, the ramifications can be especially dire. Doctors in the U.S. experience symptoms of burnout at almost twice the rate of other workers, often citing as contributors the long hours, a fear of being sued, and having to deal with growing bureaucracy, like filling out clunky and time-consuming electronic medical records. Burned-out doctors tend to make more medical errors, and their patients have worse outcomes and are less satisfied. Doctors also have higher rates of suicide than the general population, according to the American Foundation for Suicide Prevention.

The economic impacts of burnout are also significant, costing the U.S. some $4.6 billion every year, according to a new study published in the journal Annals of Internal Medicine.

To calculate the cost, a team of researchers looked at several key measures related to physician burnout, including turnover. Using recent research and industry reports, they weighed the costs of replacing a doctor who leaves their job. “Marketing costs to advertise the position, costs of hiring, costs associated with training and starting out a physician—all of these really add up pretty quickly,” says study co-author Joel Goh, an assistant professor at the National University of Singapore and a visiting scholar at Harvard Business School. The analysis also factored in the revenue a healthcare organization loses when they have an unfilled physician position.

The researchers call these estimates conservative; they didn’t consider other expensive aspects of physician burnout, like malpractice lawsuits and lower quality patient care, because they’re difficult to quantify.

“Physicians find practicing medicine harder than ever because it is harder than ever,” writes Dr. Edward Ellison, executive medical director and chairman of the Southern California Permanente Medical Group, in an editorial accompanying the analysis. “Nearly everything a physician does in 2019 is monitored, rated, assessed, and reported. The electronic health record has many benefits but it can also be a burden, adding substantially to the time physicians spend in front of a computer screen while robbing them of what brings them joy: spending time with their patients.”

These challenges will likely grow in the U.S., thanks to an anticipated physician shortage. “Over the next 20 or 30 years, it looks as if the demands are projected to increase, and the supply is basically not going to be able to catch up,” says Goh. “We’re starting to feel some of the effects today.”

The physician-burnout problem is complex, and so demands complex solutions. Goh says he hopes these new estimates show that physician burnout is an acute economic issue, on top of the clear ethical and moral urgencies it presents. “These are not small numbers,” he says.

Write to Mandy Oaklander at mandy.oaklander@time.com.