Acetaminophen and NSAIDs for Migraine

Reviewed by: HU Medical Review Board | Last reviewed: May 2023 | Last updated: May 2023

Acetaminophen and many NSAIDs are readily available without a prescription. NSAID stands for non-steroidal anti-inflammatory drug. These medications are general pain relievers. They are commonly used as first-line acute treatment for people who have mild-to-moderate migraine attacks. People with inconsistent migraine patterns might start with a pain reliever and follow up with a stronger drug later if needed.1,2

Less commonly, NSAID injections may be used in the hospital if other treatments have failed.1

Which pain reliever works the best?

Study results can be a starting point to figure out what works best for you. But remember, what worked in a group of study participants may or may not be the best option for you.

In trials, NSAIDs generally work better than acetaminophen.2 Without head-to-head trials comparing the NSAIDs, it is difficult to say which one might work best.2 You could decide which to take based on cost, side effects, and availability.

The combination of acetaminophen/aspirin/caffeine has been proven to treat migraine. One trial compared acetaminophen/aspirin/caffeine with ibuprofen to treat severe migraine pain.3 Both treatments worked better than placebo (no treatment). Acetaminophen/aspirin/caffeine relieved pain better than ibuprofen as early as 45 minutes after taking it. The benefits continued through 4 hours after treatment.

Is aspirin an NSAID?

Yes. Aspirin is an NSAID. It works differently than other NSAIDs.

All NSAIDs relieve pain and reduce inflammation. They do this by blocking the COX enzyme. This stops the production of chemicals called prostaglandins. The difference between aspirin and non-aspirin NSAIDs is how they block COX. Aspirin binds permanently to COX. The non-aspirin NSAIDs bind temporarily to COX. This difference is the reason aspirin provides lasting protection against platelet clumping. The antiplatelet effects of non-aspirin NSAIDs are much shorter.

Does adding caffeine help pain relievers work?

Maybe. Caffeine is an ingredient in many over-the-counter headache drugs. Caffeine seems to have its own pain-relieving effects.4 It also seems to increase the pain-relieving effects of other drugs by about 40 percent.5

On the other hand, caffeine also contributes to headaches.4 If consumed regularly, the brain starts to tolerate caffeine. Withdrawal leads to symptoms such as headache, nausea, drowsiness, and more.

What are the side effects of NSAIDs?

NSAIDs can cause problems with your stomach and gut.6 These problems include constipation, diarrhea, gas, bloating, nausea, or pain. More serious complications include bleeding, stomach ulcers, or kidney problems. Signs of these complications include changes in stool or urine and weight gain, among others.

People with certain health conditions should not take NSAIDs. For example, people with certain heart problems should not take non-aspirin NSAIDs.

Even though these drugs are available without a prescription, it is a good idea to talk to your doctor about taking them. If you are taking several medications, it is important to know which of them are NSAIDs.

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 are the side effects of acetaminophen?

Unlike NSAIDs, acetaminophen does not irritate your stomach and gut. However, too much acetaminophen can damage your liver. It is very important to know which of the medications you take contain acetaminophen. Do not take more than the recommended amount.

Acetaminophen may not be safe for people with severe kidney or liver disease.7 Do not take acetaminophen if you drink 3 or more alcohol beverages per day. Allergic reactions to acetaminophen are rare, but possible.

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

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