The Harvard study was conducted in the wake of the 2015 Germanwings tragedy in the French Alps, in which a mentally ill co-pilot deliberately crashed his plane, killing himself and 149 others.
Researchers found that 426 of 3,278 pilots surveyed last year - about 13 percent - were likely suffering from depression.
Seventy-five pilots reported having suicidal or self-destructive thoughts within two weeks of taking the survey, according to the study, published Wednesday in Environmental Health.
Using those numbers, researchers estimated that about 18,000 pilots are depressed and 5,600 have been suicidal, out of the roughly 140,000 flying worldwide - half of whom fly in the United States.
Airline pilots may be grounded if they report experiencing depression, depending on whether they are being treated, according to the study's lead author, Alex Wu.
"That is a strong disincentive [to report], if that directly influences their career," he said, according to Boston.com.
"Underreporting of mental-health symptoms and diagnoses is probable among airline pilots due to the public stigma of mental illness and fear among pilots of being grounded," the study says.
"Miracle on the Hudson" pilot Chesley "Sully" Sullenberger said pilots who are not fit to fly should remain out of the cockpit.
"But we need to make pathways for them to come back to work when their issues are resolved," the retired US Airways captain, whose father took his life after a battle with depression, told CBS News.
"It's likely given these statistics, I probably have flown with someone who had thoughts. They just didn't share them with me," Sullenberger said. "Self-reporting is critically important."
Despite the findings, public confidence in airline pilots should not take a hit, the authors said.
"Flying is safe and this study doesn't change that," senior study author Joseph G. Allen told the LA Times.
The Federal Aviation Administration has not called for routine psychological evaluations, saying there is no proof it would improve safety, CBS News reported.
But a US advisory panel has recently called for heightened measures to spot and treat mentally ill pilots to prevent the kind of breakdowns that led to the Germanwings disaster, a source told the Washington Post.
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