It’s known that both non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants can cause gastrointestinal (GI) bleeding, but now a study shows that they can also increase the risk of intracranial bleeding when taken together.

While neither medication has been associated with the risk on its own, Korean researchers found that in patients using the combination of antidepressants and NSAIDs, the risk of intracranial hemorrhage was higher in the next 30 days compared to those patients using only antidepressants.

The Study Findings

The researchers of the study, published in The BMJ, analyzed data from the Korean nationwide health insurance database to obtain 4,145,226 people who were first-time antidepressant users from 2009-2013. They also accessed NSAID prescriptions and hospital records to identify any admissions for intracranial hemorrhages with a month of a new antidepressant prescription.

They found men were 2.6 times more likely to suffer an episode of bleeding in the brain, and women were 1.2 times more likely. There were no differences found in type of antidepressant and the age of the subject.

“The idea that antidepressants, especially selective serotonin reuptake inhibitors (SSRI), increase risk of bleeding is well-known, especially for bleeding in the stomach,” says Rajnish Mago, MD, Director, Mood Disorders Program, Thomas Jefferson University, and Associate Professor of Psychiatry and Human Behavior at Jefferson Medical College in Philadelphia. Platelets, the clotting cells in the blood, contain the same serotonin transporter molecule that brain cells do, explains Mago. In the platelets, when antidepressants block reuptake of serotonin, this reduces the ability of platelets to stick together and make a plug to stop any bleeding.

For this reason, he also prescribes a proton pump inhibitor (PPI), such as Prilosec or Nexium, when prescribing SSRIs to reduce of risk of GI bleeding. The brain bleeding, he says, is more difficult to prevent.

Should You Worry?

Not everyone who takes both an antidepressant and a NSAID is at equal risk for intracranial bleeding, but if you have certain risk factors, you should discuss the risk with your doctor. “Yes, the risk is very small, but given the seriousness of the matter, it’s something that cannot be ignored."

While in this particular study the researchers did not find older people or those on warfarin had a greater increase in risk, older age may be relevant. That’s because the older population tends to have greater risk factors for intracranial bleeding, including high blood pressure, diabetes, and previous stroke.

What You Can Do

There are different classes of antidepressants, so one that doesn't have has much impact on serotonin may be an option. If continuing SSRIs is most beneficial, consider other pain relief options. Alternatives to NSAIDs include acetaminophen (Tylenol) or an opioid (Percocet). For example, Mago explains that since an opioid is not a NSAID it would be okay to prescribe as a post-surgery pain relief. While doctors may be hesitant to prescribe them because of their addiction possibility, in the case of combined antidepressant use it may be a better choice. Plus, the risk of addiction in taking the drugs for a few days or a week is small.

It all comes down to a collaborative relationship with your doctor, Mago stresses. Depression often goes hand in hand with chronic conditions that require pain relief. You should know that bleeding is a risk, and also know that there are other options available—for both pain relief and depression. Talk to your doctor about finding the best options for you.

Rajnish Mago, M.D., Director, Mood Disorders Program, Thomas Jefferson University, reviewed this article.


Ju-Young Shin, Mi-Ju Park, Shin Haeng Lee, So-Hyun Choi, Mi-Hee Kim, Nam-Kyong Choi, Joongyub Lee, Byung-Joo Park. “Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study.” The BMJ, doi: 10.1136/bmj.h3517, published online July 14, 2015.

Rajnish Mago, M.D., interview with source, October 19, 2015.