Zoloft and Ibuprofen: Interactions and Side Effects

By Alicia Wooldridge, MD
Medically reviewed checkmarkMedically reviewed
May 25, 2022

Most of us think nothing of taking over-the-counter (OTC) pain reliever when an everyday headache, muscle soreness, or other discomfort crops up.

But if you take certain prescription medications, you need to be mindful of your OTC drugs.

For example, if you check the prescription insert, the antidepressant Zoloft includes a warning that taking it with ibuprofen can increase the risk of bleeding.

Luckily, there are other medications you can take to address pain.

In this article, we’ll explore potential interactions between Zoloft and ibuprofen, precautions about this drug combination, safe alternatives, and when to see a doctor if you take Zoloft.

Zoloft and Ibuprofen Interactions

Zoloft and ibuprofen can individually have a thinning effect on the blood.

Zoloft is the brand name of the selective serotonin reuptake inhibitor (SSRI) sertraline.

It is commonly prescribed for major depressive disorder and anxiety.

It increases the amount of serotonin in the brain by slowing the body’s absorption of this neurotransmitter.

In addition to regulating mood, serotonin plays a role in blood clotting.

When absorption slows, so does the time it takes for blood to coagulate, or clump together.

Due to this decreased clotting, Zoloft can lead to a greater risk of bleeding, either externally (if, for example, you cut yourself) or internally (such as if you have an ulcer). 

Ibuprofen, which is sold under the brands Advil and Motrin, is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve pain.

It can also interfere with blood clotting, which can increase the risk of bleeding. (This happens with other NSAIDs such as aspirin and naproxen too.)

If the use of both Zoloft and ibuprofen overlaps for short periods of time or rarely, there is not as much risk of bleeding.

But if both are regularly consumed at the same time, for long periods of time, the risk can increase: It can be four times greater than the risk with taking NSAIDs alone and 10 times higher than the risk with taking SSRIs alone.

Feeling Down?

Take our free assessment and learn about your options.

Get Started
Doctor's image

Other drug interactions of Zoloft

Zoloft has some potentially serious drug interactions, so always tell your healthcare provider if you take any prescription medications, OTC drugs, supplements, or vitamins.

In particular, if you combine Zoloft with other medications that affect serotonin levels, a serious and potentially life-threatening complication known as serotonin syndrome can occur.

Do not take Zoloft with the following medications:

  • Anticoagulants
  • Monoamine oxidase inhibitors (MAOIs)
  • St. John’s wort
  • Eliglustat
  • Isocarboxazid
  • Lomitapide
  • Flibanserin
  • Procarbazine
  • Thioridazine
  • Phenelzine
  • Pimozide
  • Selegiline
  • Tranylcypromine

Risks and Precautions

Most people who take Zoloft and occasionally take ibuprofen won’t experience any significant side effects.

However, any other medications that slow clotting time can lead to further risks.

Additionally, people who have certain bleeding disorders or coagulation problems may be at higher risk for complications.

Other medical conditions or situations that can increase the risk of serious side effects or complications from combining Zoloft and ibuprofen include:

  • Kidney or liver disorders
  • Gastrointestinal disorders like GERD or ulcers
  • The use of aspirin or blood thinners
  • Being older

If you notice any of the following symptoms, stop taking ibuprofen and contact your healthcare provider immediately:

  • Black, red, or tarry bowel movements
  • Unusual or excessive bleeding (nosebleeds, cuts, etc.)
  • Easy or excessive bruising
  • Bleeding from the gums
  • Coughing up blood or vomiting what looks like coffee grounds
  • Heavy menstrual flow
  • Signs of blood loss, such as lightheaded or dizzy feelings, weakness, or headache

Tell your doctor if you have ever had allergic reactions or adverse reactions to any ingredients in Zoloft.

Possible Alternatives for Zoloft

There are many treatment options for anxiety and depression.

If you need to take ibuprofen, your healthcare provider may suggest one of the following rather than Zoloft:

  • Xanax: A benzodiazepine, Xanax is in a different class of drugs than Zoloft. It works on different brain chemicals and is only intended for short-term use. Xanax is a controlled substance and may be addictive or habit-forming. It may be more effective than Zoloft at treating short-term or acute episodes of anxiety.

Safer alternatives to ibuprofen

If you need to continue taking Zoloft, acetaminophen (Tylenol) is the safest alternative to ibuprofen for pain, fever, or headache relief because it isn’t an NSAID and doesn’t increase the risk of bleeding.

Though aspirin and naproxen (Aleve) are ibuprofen alternatives, both are NSAIDs and come with the same risk of bleeding.

Feeling Down?

Take our free assessment and learn about your options.

Get Started
Doctor's image

When to See a Doctor

If you take Zoloft and require a pain reliever, ask your doctor whether it is safe to occasionally use ibuprofen or whether you need an alternative.

Also see your healthcare provider if you take ibuprofen regularly and need to find a replacement anti-anxiety or antidepressant medication for Zoloft.

If you take Zoloft and ibuprofen and experience symptoms of increased bleeding that do not resolve on their own, promptly see your healthcare provider.

Internal bleeding from drug interactions does not always cause immediate symptoms, but it can lead to serious and severe complications. 

How K Health Can Help

Think you might need a prescription for Zoloft (Sertraline)?

K Health has clinicians standing by 24/7 to evaluate your symptoms and determine if Zoloft is right for you.

Get started with our free assessment, which will tell you in minutes if treatment could be a good fit. If yes, we’ll connect you right to a clinician who can prescribe medication and have it shipped right to your door.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Alicia Wooldridge, MD

Dr. Alicia Wooldridge is a board certified Family Medicine physician with over a decade of experience.

Close button

Get confidential, affordable mental health treatment

Start your free assessment now
Image of pill bottle
K Health logo (used on certain page templates)