Non-Steroidal Anti-Inflammatories for the Acute Treatment of Migraine

Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used medications for many pain conditions, and can be very effective for the treatment of migraine. There are several reasons to consider using this class of medications:

1. NSAIDs may be more effective deep into the headache attack, when the pain has spread throughout the head, and even into the neck and shoulders. This spread of pain is called central sensitization, in which the pain spreads as the attack progresses. Central sensitization is also associated with the dislike of light, noise, smells, touch, and movement so common at the peak of a migraine.

2. NSAIDs are helpful with wake-up early morning headaches which have likely progressed during the night, so that when someone with a migraine wakes up, the migraine is full-blown, and less responsive to a triptan.

3. NSAIDs can be used be used to increase the effect of migraine-specific medications. They can be added to most medications already being taken for a migraine, possibly lowering the chance of the headache coming back, also called recurrence.

4. Triptans do not work for all patients. It is estimated that triptan tablets are ineffective in up to 40% of patients, and in these individual, NSAIDS may work better than triptans.

5. Pain in migraine occurs through two pathways, inflammation and blood vessels getting big (dilation). Triptans do not work against the inflammation, although they reverse the blood vessel dilation. NSAIDs block the inflammation. Therefore, taken together, NSAIDs and triptans can work together, and the whole can be greater than the sum of the parts.

6. NSAIDs can generally be used in the setting of vascular disease. Unlike the usual migraine-specific medications such as triptans or dihydroergotamine (DHE), NSAIDs do not narrow arteries.. Individuals who have had a heart attack will still need to discuss NSAID use with their cardiologist, as NSAIDs are not entirely risk-free. Clinical trials of some NSAIDs have shown an increased risk of heart attacks and stroke, but this risk differs with different NSAIDs.

7. Menstrual migraine is one of the most challenging forms of migraine, and NSAIDS, especially when added to a triptan, will attack both pain pathways so that inflammation as well as blood vessel dilation are suppressed.

8. Unlike narcotics, NSAIDS are not habit forming, and yet can be highly effective.

NSAIDs can be administered in pill form (such as ibuprofen, naproxen), by injection (such as ketorolac or Toradol), dissolved in water, ((diclofenac potassium for oral solution/Cambia), or through nasal spray ( nasal ketorolac/Sprix).

Nasal ketorolac or SPRIX is FDA approved for the more general category of moderate to severe pain. It is not specifically FDA approved for migraine, but does bypass the GI tract for patients who are vomiting.


Treating migraines fast is very important, not only for more rapid relief, but also because as the migraine progresses, the patient’s gut becomes more sluggish and less effective at absorbing pills or even melt formulations. For this reason non-tablet treatment is one way to get faster and more effective relief.

As of now, the only FDA approved prescription NSAID for the treatment of migraine specifically is Cambia, a dissolvable diclofenac. It comes in the form of a flavored powder that is poured into a small amount of water, and then drunk. Other prescription NSAIDs are not FDA approved for migraine.

Cambia consists of 50 mg of diclofenac, an NSAID that at 2 hours into migraine, has been shown to be as effective as the tablet form of sumatriptan, the most commonly used triptan. Unlike the generic tablet of diclofenac, Cambia begins to give pain relief in 15 minutes.

In Summary: Use of an NSAID with or without a triptan, offers fast relief, does not constrict arterial blood flow, provides additional relief of inflammation, is effective late into a migraine attack, is helpful in reversing the pain spread called central sensitization, and can be especially helpful for menstrual migraine.

Deborah E. Tepper, MD

Center for Headache,

Cleveland Clinic