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Nonsteroidal anti-inflammatory drugs, commonly referred to as NSAIDs, are used to alleviate fever symptoms and reduce pain. Most people who take over-the-counter NSAIDs use them to ease the occasional headache or muscle pain. But they also provide quick relief for an estimated 52 million Americans— mostly older adults— with arthritis. In these cases, prescription-strength NSAIDs drastically improve quality of life with few noticeable side effects.

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“These are some of the most popular drugs in the world,” says Dr. Myron Tong, director of liver research at the Huntington Medical Research Institutes in Pasadena, California. “And as the American population ages, usage will probably increase too.”

Research suggests that regular, heavy use of these drugs increases the long-term risk of heart attack, stroke, liver damage and ulcers. These medications may also interfere with antidepressants.

For most people, over-the-counter NSAIDs are relatively safe to use for minor aches and pains. But daily use increases the risks of conditions that may be more serious. Here’s what to know about the risks.

Heart attack and stroke

There are over a dozen NSAIDs on the market, including over-the-counter versions like ibuprofen (Advil) or naproxen (Aleve), and prescription varieties like celecoxib (Celebrex). Most carry some risk of heart attack and stroke, especially when taken in high doses.

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The Food and Drug Administration (FDA) says that risk is higher than previously thought. Last month, the FDA announced it will strengthen the label warning that prescription NSAIDs increase the chance of heart attack and stroke. The warnings do not apply to aspirin, which is often taken at low doses for heart attack prevention. The FDA will request updates to over-the-counter NSAID labels in the future, according to the agency’s website.

Most NSAIDs bind to a key protein in the blood. “They likely reduce albumin, a substance that protects arteries against spasm and narrowing, and reduces the risk of blood clotting,” says Dr. Ronald J. Scheib, cardiologist of Pritikin Longevity Center in Miami, Florida.

Patients without a history of heart disease also face an increased risk of heart attack and stroke from prescription and over-the-counter NSAIDs, according to the FDA’s panel on NSAID safety. That panel found that estimates of increased risk range from 10 percent to more than 50 percent for serious cardiovascular events.

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The risk is greater for those who have been diagnosed with any type of heart disease, Scheib says.

Interaction with antidepressants

Research has found that some NSAIDs, particularly ibuprofen varieties like Advil or Motrin, may make some antidepressants less effective. Specifically, selective serotonin reuptake inhibitors (SSRIs) like Prozac, Lexapro and Paxil may not work as well when combined with NSAIDs.

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In a study involving more than 1,500 SSRI antidepressant users, those who took NSAIDs were found to be more likely to be resistant to antidepressant treatment. The analysis, published in the Proceedings of the National Academy of Sciences, showed that 45 percent of SSRI users who took NSAIDs responded to antidepressants, compared with 55 percent of people who didn’t take NSAIDs.

Liver damage

NSAIDs present a minuscule risk of liver damage for most people, especially those who take them only occasionally. However, there is a group at increased risk.

“I advise my patients with liver inflammation or kidney disorders not to use NSAIDs at all,” Tong says. “It’s a small group, but people with hepatitis, cirrhosis, or who have had kidney failure should generally not take NSAIDs.”

These patients are at an increased risk of toxicity to the liver, which could lead to failure. For people without those problems, risk of liver injury is around 1 in 100,000, Tong says.

Ulcers

Several studies have found that over-the-counter NSAIDs, especially aspirin, can cause ulcers in the stomach and the small intestine. According to a 2010 safety review in the Oxford journal Rheumatology, the risk of complications in the stomach or small intestines in over-the-counter NSAID users is four times as great as in non-users. It also found the risk of peptic ulcers was five times greater in over-the-counter NSAID users than in non-users.

Safely using NSAIDs

Those with kidney, liver, or heart diseases should be more cautious and avoid using prescription-strength NSAIDs.

“There are other options to reduce pain for those people at a higher risk,” says Tong, the director of liver research in Pasadena. “Your doctor can help you make that decision.”

For the majority of people, the risk of taking NSAIDs is small enough that there’s no reason to not take them from time to time.

“For someone with just a headache or some joint pain, take the recommended dose on the bottle, but never more,” says Scheib, the cardiologist. If you’re not finding relief from NSAIDs, he says, it’s time to see a doctor.