“NSAIDs target inflammation and pain and thus often work on the pain receptors to block and decrease pain sensation,” says Doris Kung, DO, a neurologist and associate professor at Baylor College of Medicine in Houston. “In migraine, these drugs seem to target the parts of the brain, brainstem, and cranial nerves that may be involved in generating headache pain.” As a result, they can also block the brain processes that cause migraine attacks, Dr. Kung adds. Not surprisingly, NSAIDs have long been a mainstay of migraine treatment, according to the American Migraine Foundation (AMF). Although triptans such as sumatriptan (Imitrex) and naratriptan (Amerge) are more often the first-choice treatment option for migraine, NSAIDs can be effective at relieving some of its symptoms, says Merle Diamond, MD, a headache specialist with the Diamond Headache Clinic and an assistant professor of medicine at the Chicago Medical School. However, like all medications NSAIDs have side effects — some significant — and can cause a common migraine complication called “medication-overuse headache.” Here’s how to use NSAIDs — safely — for migraine so that you get the most out of these widely used pain drugs.

What Are NSAIDs?

NSAIDs are a class of pain relievers designed to block the production of specific body chemicals that cause inflammation, according to Cleveland Clinic. They’re available in both prescription and nonprescription strength, the latter as over-the-counter (OTC) products found in drugstores and supermarkets. They can be used to treat a variety of pain conditions, including:

Back painDental and mouth painMenstrual crampsMuscle achesOsteoarthritisRheumatoid arthritis

In general, NSAIDs are effective at treating pain caused by slow tissue damage, such as arthritis pain.

NSAIDs for Migraine

The American Academy of Family Physicians (AAFP) notes that oral NSAIDs can be effective for people with mild to moderate migraine. Oral NSAIDs include:

aspirin (sold under several brand names, including Bayer and St. Joseph)celecoxib (Celebrex and Elyxyb)diclofenac tablets (Cataflam, Voltaren, Zipsor, among others) and diclofenac powder (Cambia)flurbiprofenibuprofen (Motrin and Advil Migraine)indomethacin (Indocin)ketorolac (Toradol IM or Sprix NS)mefenamic acidnabumetonenaproxen (Aleve and Anaprox)

NSAIDs are also components of suggested combination treatments for mild to moderate migraine. Examples include Excedrin Migraine, which is a combination of acetaminophen, aspirin, and caffeine, and Treximet, which combines sumatriptan and naproxen, according to the AAFP. Aspirin is considered an OTC product, meaning it can be used without a doctor’s prescription. Excedrin is also an OTC, while diclofenac, ibuprofen, and naproxen come in both prescription and nonprescription strengths. “The prescription doses of these medications are higher than the over-the-counter options,” Dr. Kung explains. Celecoxib, flurbiprofen, indomethacin, ketorolac, mefenamic acid, and nabumetone are only available with a doctor’s prescription.

Using NSAIDs for Migraine

If your doctor recommends an NSAID for migraine, the dose you take will depend on the specific drug you use and the severity and nature of your symptoms, according to Dr. Diamond. Your risk for certain side effects associated with NSAID use will also help determine your dose, she adds. Generally, NSAIDs such as diclofenac powder and ketorolac are recommended to treat migraine attacks, because they start to work faster after you take them, the American Headache Society (PDF) notes. Diclofenac tablets, ibuprofen, indomethacin, and naproxen can take longer to work, so they’re often recommended for people whose attacks are longer in duration, it says. For most NSAIDs, your doctor will advise you to take them as needed — at the beginning of a migraine attack or beforehand, following exposure to a migraine trigger — with certain restrictions, Diamond says. This is to limit possible side effects associated with their use, she explains. NSAIDs should be used to relieve symptoms of migraine, not to prevent attacks, she adds.

NSAIDs Side Effects and Safety Concerns

Although NSAIDs are generally safe, Kung says, they can irritate the lining of the stomach or intestines, which can be problematic for people with peptic ulcers, acid reflux, GERD, irritable bowel syndrome, and other gastrointestinal (GI) disorders, according to the American Migraine Foundation. Heartburn (or acid reflux) and diarrhea are also common side effects associated with NSAIDs, it notes. NSAID use can also cause fluid retention, or edema, the accumulation of excess fluid that causes swelling in the arms and legs as well as in certain organs of the body, including the eyes, heart, and lungs. However, this is rare, particularly with as-needed use. NSAIDs can impair kidney or liver function when taken daily or near-daily, which is why your doctor will recommend that you only use them when needed, Diamond says. Similarly, these medications can also increase your risk for heart attack and stroke, so if you have a history of these conditions, NSAIDs may not be right for you, she adds. In addition, people who take blood thinners can’t take NSAIDs. Because of these side effects, you shouldn’t exceed the maximum daily dose for an NSAID (a number that varies depending on the drug and your risk for certain side effects). Also, don’t assume that taking more of an NSAID will make it more effective, Diamond warns. This can increase your risk for certain side effects. “When I started treating headache patients more than 30 years ago, we often recommended NSAIDs be taken daily, to prevent attacks,” Diamond notes. “However, as we learned more about these side effects, we moved away from that and toward their use to treat attacks.” Beyond these NSAID-specific side effects, people who use the drugs are susceptible to a phenomenon called medication-overuse headache, she adds. This complication typically occurs when you take NSAIDs or triptans more than once or twice a week, as these medications can alter the serotonin system in the brain and interfere with the body’s pain response, which causes increased sensitivity to pain. Among OTC NSAIDs, Excedrin Migraine and Advil Migraine both carry warnings for medication-overuse headache.

Are NSAIDs Effective for Migraine?

NSAIDs work by blocking chemicals called cyclooxygenase (COX) enzymes that cause inflammation, or swelling. In the case of migraine, they block the enzyme’s function in the brain. Because of their ability to block COX, NSAIDs work well for people with mild to moderate migraine symptoms, but they aren’t really an option for those with more severe symptoms, Diamond explains. “There are a number of clinical studies where they’ve been shown to be efficacious in the acute treatment of migraine,” she adds. Research suggests that the medications in this class provide “a modest but significant benefit,” at least compared with a placebo (a sham or fake treatment that provides no clinical benefit). However, in the few studies that have compared an NSAID with a triptan, the former has performed nearly as well. In general, NSAIDs are more effective when taken early in a migraine attack, or soon after the onset of symptoms, according to the American Migraine Foundation. Prescription NSAIDs contain higher doses, but OTC versions can also provide symptom relief, Diamond says. “More isn’t necessarily better,” she adds. Prescription triptans are usually the first-choice treatment for people who have more serious migraine symptoms, but NSAIDs can be an option for people who can’t take these medications, due to a history of heart disease or stroke, the AMF adds. NSAIDs are often less expensive than triptans, making them an option if cost is an issue, the AMF notes. Still, at least one prescription product — sumatriptan combined with naproxen (Treximet) — combines an NSAID with a triptan, an approach called “layering.” Taking an NSAID and a triptan together may be more effective at migraine relief than taking either drug alone, according to the AMF. Excedrin Migraine, which combines the pain medication acetaminophen with the NSAID aspirin and caffeine is another example of “layering.” “Excedrin contains acetaminophen, aspirin, and caffeine and thus can target headache relief through several mechanisms of action,” Kung explains. “Although some people may respond to caffeine and acetaminophen, others may find that these aren’t effective, and these components can still cause medication-overuse headaches.” Like all migraine treatments, NSAIDs may take several weeks — or even months — to work. You should give the drug recommended by your doctor time to work before trying another option. And, even if one NSAID doesn’t relieve your symptoms, another one might, Kung says.