A new study in the journal The BMJ finds that the risk of intracranial hemorrhage – bleeding that occurs in or around the brain – is increased when one combines antidepressants with non-steroidal anti-inflammatory drugs (NSAIDS) like ibuprofen or naproxen. Since depression and chronic pain often go hand-in-hand, and millions of people may take the two meds together, the study results are particularly relevant. It’s important to note, however, that this study looked only at prescription NSAIDs, so doses may have been higher than what one might take with an over-the-counter versions. Still, the results raise questions about whether it’s advisable to combine the two drugs over the long term, or at all.
The researchers, from Seoul National University College of Medicine, looked at data from over four million people who had started taking antidepressant medication between 2009 and 2013. About half were also prescribed an NSAID, like ibuprofen or naproxen. The team used hospital records to see who was admitted for intracranial bleeding in the 30 days after being prescribed the NSAID.
It turned out that people who began taking both medications had a 60% greater risk of bleeding around the brain than people taking only antidepressants. There was no significant difference in the risk among the different types of antidepressants (SSRIs, SNRIs, and tricyclics).
The risk of intracranial bleeding was especially heightened in men who took both antidepressants and NSAIDs. Their risk was about 2.6 times higher than men who took antidepressants alone, whereas the risk for women was only about 1.2 times higher than women who took just the one med.
The big caveat is that the team only looked at bleeding that occurred within 30 days of the NSAID prescription: The risk might be different -- possibly higher -- over the long-term. That said, the absolute risk of developing brain bleeding was low, at about 5.7 per 1000 people studied.
We also don't know how the effect of over-the-counter (OTC) painkillers may differ from prescription. "It might be a future study -- there are many possibilities," says study author Byung-Joo Park. "Therefore, we should consider every case. For example, the risk might be higher because OTC NSAIDs are used without any professional advice or monitoring. Or the risk could be lower, because OTC NSAIDs consumers might be healthier users compared with prescription."
The mechanism isn’t totally clear, but each medication appears to have an inhibitory effect on platelets, and each is thought to slightly increase the risk of bleeding on its own (for instance, SSRI antidepressants and NSAIDs are both known to increase the risk of gastrointestinal bleeding). Though neither medication by itself seems to increase the risk of intracranial bleeding, perhaps the two together may have a slight effect.
This study comes just days after the FDA strengthened its warning about the risk of heart attack and stroke from NSAIDs alone. The FDA notes that although heart attack and stroke risk may occur within weeks of beginning to take an NSAID, the risk is likely higher with long-term use.
Since depression and pain often go together, given their shared neurobiological pathways, the new study may be especially relevant. About 65% of people with major depression also have chronic pain, according to an editorial that accompanied the main study.
More work will be needed to understand the connection and all the mechanisms involved. In the meantime, if you’re on one or both of these medications, talk with your doctor about the risks, if you haven’t already, since he or she can give you more personalized advice. And as always, check with your doctor before going on or off a medication, particularly a prescription.
