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NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been around for centuries and are some of the oldest and most widely used medications. In fact, 3500 years ago, the Greek physician Hippocrates prescribed an extract from willow bark to treat pain, fever, and inflammation.1

In the 17th century, scientists discovered salicin as the active ingredient in willow tree bark. The NSAID class of drugs originated more than two hundred years later, in 1899, when Bayer introduced acetylsalicyclic acid (aspirin) into the market.1

Many NSAIDs are readily available as over-the-counter drugs, and therefore don’t need a prescription. However, some higher strength NSAIDs used as rescue medications for migraine are only available by prescription. As a class, NSAIDs are used to lower fevers as well as to treat inflammation and a variety of pain from arthritis, muscle aches, menstrual cramps, and migraine attacks.2

NSAIDs are most often used for mild-to-moderate migraine. They are often used as a first choice medication, either alone or in combination, since they are effective, less expensive, and have fewer side effects than many migraine-specific medications.3

NSAIDs are not effective for long-term prevention. Additionally, they should not be used more than twice a week to treat head pain, because overuse can lead to medication-overuse headaches or chronic daily migraine.4

NSAIDs appear to be particularly useful for menstrual migraine and migraine caused by exercise or exertion.

How do NSAIDs work?

NSAIDs work by blocking certain chemical signals in the body that cause inflammation, or swelling. These chemicals are known as cyclooxygenase (COX) enzymes.1

To treat migraine, NSAIDs are also available in combination with caffeine, which enhances their antimigraine effect. Some pain relievers also contain a combination of acetaminophen, aspirin, and caffeine.3

What are some common NSAIDs?

Over-the-counter NSAID medications for migraine and other headaches include:

  • Aspirin (available as Anacin®, Bayer®, Bufferin®, Ecotrin®, Excedrin®)
  • Ibuprofen (available as Advil®, Motrin IB®, Nuprin®)
  • Naproxen (available as Aleve®)

NSAIDs available by prescription for migraine include:

  • Anaprox (naproxen sodium)
  • Cambia® (diclofenac potassium)
  • Cataflam® (diclofenac potassium)
  • Indocin® (indomethacin)

NSAIDs come in the following forms:

  • Tablet
  • Liquid
  • Chewable
  • Capsule
  • Suppository

Indomethacin is a prescription medicine that also comes in a rectal suppository, which may be useful for people who feel nausea when they have migraine.4

What are some side effects of NSAIDs?

The most common side effects of NSAIDs are upset stomach, ulcers, heartburn, and rash. Some users also experience stomach or GI bleeding, vomiting, and changes in liver function.5

People who have heart disease should not take an NSAID, including over-the-counter NSAIDs, without first talking to their doctor. Some NSAIDs may interfere with medicines prescribed to patients with heart disease.

These are not all the possible side effects of NSAIDs. Patients should talk to their doctor about what to expect with treatment with NSAIDs.

What else should I know about NSAIDs?

NSAIDs are best taken with food to reduce the risk of digestive problems. If taken too frequently or for long periods of time NSAIDs can also lead to medication overuse, or rebound, headaches. People who have been taking NSAIDs regularly should not stop suddenly.

Older people or those with serious health problems may have other side effects, which are seen less often, such as confusion, swelling of the face, feet, or lower legs or a decrease in urine. Children should not take aspirin, especially if they have recently had a cold or virus.

Health care providers do not recommend taking NSAIDs if you have ulcers, esophageal reflux, kidney disease, or the triad of aspirin sensitivity, nasal polyps, and asthma.4

Written by: Sara Finkelstein | Last reviewed: August 2019
  1. P. N. Praveen Rao and Edward E. Knaus. Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond. J Pharm Pharmaceut Sci (www. 11 (2): 81s-110s, 2008. Accessed May 10, 2018.
  2. Pain Relievers: Understanding Your OTC Options. Family American Academy of Family Physicians. Accessed May 10, 2018.
  3. Zahid H Bajwa, MD and Jonathan H Smith, MD. Acute treatment of migraine in adults. UpToDate. Published January 15, 2018. Accessed May 10, 2018.
  4. Commonly Used Acute Migraine Treatments. American Migraine Foundation. Published September 21, 2016. Accessed May 10, 2018.
  5. Headache Medications. The Cleveland Clinic. Published July 8, 2014. Accessed May 10, 2018.