Key takeaways

Taking Zoloft and ibuprofen together slightly increases the risk of bleeding, but short-term use is generally considered safe.
Zoloft and ibuprofen both affect the body’s ability to form blood clots, potentially leading to a greater chance of unwanted bleeding when used together.
People with pre-existing conditions like gastrointestinal disorders, kidney or liver issues, or those taking blood thinners are at a higher risk for bleeding when combining Zoloft and ibuprofen.
If concerned about the risk of bleeding, it’s advised to use acetaminophen (Tylenol) instead of ibuprofen with Zoloft, as it does not have the same risk of increasing bleeding.

If you take the antidepressant Zoloft, you may have noticed that your prescription insert says taking ibuprofen with Zoloft increases your risk of bleeding. It’s one in a long list of potential adverse effects, most of which, you assume won’t happen to you.

When that familiar throbbing in your forehead starts, you might remember that warning and wonder, “Is taking Zoloft and ibuprofen safe?” While it’s not always obvious when two medications might have serious a drug interaction, for most people this particular danger is really quite small.

Should you avoid taking Zoloft and ibuprofen together?

“The short answer is that there is a very small likelihood of increased risk of bleeding when taken in combination, but it is likely safe for use for short periods of time,” says Dr. Carly Snyder, MD, a psychiatrist based in New York.

You may have heard that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, can cause stomach problems like bleeding or ulcers. The effect that’s lesser known? Adding an antidepressant, such as Zoloft (sertraline), ups those chances. Zoloft slows down your body’s absorption of serotonin, which helps improve mood. But serotonin has another role: It encourages platelets to clump together and form clots. When platelets absorb less serotonin, your blood doesn’t clot as well. Ibuprofen—commonly sold under the brands Advil or Motrin—also thins your blood in the process of relieving your fever, aches, or pains. Less clotting means a greater likelihood of unwanted bleeding.

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Dr. Snyder says that taking just Zoloft increases your chance of GI or stomach bleeding by roughly one and a half to two times. If you’re taking sertraline and ibuprofen (or any NSAID), the likelihood of bleeding increases to four times.

“Since the two medications have a synergistic effect when taken together, meaning that you end up with more of each medication when taken together compared to when each is taken alone, the side effects will then also be increased,” says Danielle Plummer, Pharm.D., a pharmacist based in Nevada. Some studies show that taking these two medications together increases your chances of bleeding by 10 times, she explains.

Certain patients are at a higher risk for bleeding

Most people taking Zoloft won’t experience any issues with occasional ibuprofen use. “People who have pre-existing conditions that render their platelet counts already low … or who have inherited dysfunctional platelets like Von Willebrand disease, may need to exercise more caution,” explains Dr. Snyder.

Patients with the following medical conditions are at higher risk, according to Dr. Plummer:

gastrointestinal (GI) disorders, including GERD (reflux) and ulcers
kidney disorders
liver disorders
patients taking warfarin or aspirin (or any other medications that impacts the likelihood of bleeding)
elderly patients

Dr. Plummer goes on to explain there are some signs that there’s been an interaction between the two drugs. These include:

unusual or excessive bleeding (including cuts or nosebleeds)
unusual or excessive bruising
red, black, or tarry stools
bleeding from gums after bruising (that is excessive or unusual)
coughing up fresh blood or dried blood that looks similar to coffee ground.
heavier than usual menstrual flow, accompanied by headache and/or dizziness
Symptoms of blood loss such as lightheadedness, dizziness, headache, or weakness.

If you notice any of these symptoms, you should seek medical attention immediately, and discontinue taking the ibuprofen.

Can I take acetaminophen with Zoloft?

Both Dr. Plummer and Dr. Snyder agreed that an Advil here or there is probably okay. However, they both advised against chronic usage of the two medications together. If you’re worried, take Tylenol (acetaminophen) instead. It’s not an NSAID, so it doesn’t increase bleeding.