Combining antidepressants and a commonly used over-the-counter painkiller can have dangerous side effects, according to a recent study.

Korean researchers found that of more than 4 million people prescribed a first-time antidepressant, those who also used nonsteroidal anti-inflammatory drugs (NSAIDs) had a significantly higher risk of intracranial hemorrhage.

Intracranial hemorrhage refers to bleeding under the skull that can lead to permanent brain damage or death. NSAIDs reduce inflammation and pain, and are commonly used to provide relief for headaches, arthritis, backaches, and sprains. Popular brands include Excedrin, Advil, Motrin, and Aleve.

The investigators, led by senior researcher Dr. Byung-Joo Park, studied records from Korea’s national health insurance program to find more than 4 million people given a new prescription for an antidepressant between 2009 and 2013. Half were also using an NSAID.

Park’s team found that NSAID users were 60 percent more likely to suffer an intracranial hemorrhage within 30 days of starting an antidepressant – even with age and chronic medical conditions taken into account.

While they found no statistical differences in risk of bleeding between ages, being male was a common factor for a higher risk.

There was no indication that any particular type of antidepressant carried a greater risk than others, said Park, a professor of preventive medicine at Seoul National University College of Medicine.

He said that antidepressant users should consult their doctor before taking NSAIDs on their own.

Park also pointed out that the study looked at the risk of brain bleeding within 30 days, so the findings may not apply to people who’ve been using an antidepressant and an NSAID for a longer period without problems.

In an accompanying editorial, Dr. Stewart Mercer at the University of Glasgow and colleagues at the University of Cambridge said the results are concerning. They pointed out that both types of drug are widely used, and that co-morbidity of the conditions for which these drugs are used is very high: 65% of those with major depression also have chronic pain. They urge doctors to be extra vigilant in terms of prescribing behavior and discussing the risks with patients.