100 Migraine Drugs, A to Z: clopidogrel

Clopidogrel (Plavix) was not on my original list of 100 migraine drugs, but I decided to add it after another mention of this drug at the last congress of the International Headache Society in Dublin (since I keep adding drugs and new ones are being released, the list will exceed 100).

Patients who suffer from migraines, especially those who have auras, have a higher incidence of a persistent opening between the left and the right side of their heart, called patent foramen ovale or PFO. PFO is found in 25% of the general population, is usually small and causes no symptoms. When it is large, it needs to be closed, which can be done through a vein in the groin. Unfortunately, studies that aimed to relieve migraines by closing the PFO did not show much benefit. However, blood thinners used after the procedure may have helped some patients.

I first mentioned clopidogrel in a blog post from 2007 when describing a British doctor’s experience with a few of his patients. In another blog post from 2015 I mentioned a study that showed that clopidogrel with aspirin was more effective in improving migraines than aspirin alone. A study comparing aspirin and clopidogrel showed them to be equally effective in improving migraines in patients with a PFO.

In the study presented in Dublin by two Chinese doctors PFO was found in 151 out of 266 (57%) of all migraine patients, of whom 65 the opening was large. PFO was found in 59 out of 84 (70%) of all migraine with aura and 36 patients had a large opening. 27 migraine patients who did not respond to standard medical therapy were given clopidogrel, 75 mg a day for 3 months. 22 patients completed this study. Headache frequency, severity and duration were significantly decreased by addition of this drug. Migraine-related disability was also reduced.

Aspirin, clopidogrel as well as prasugrel (Effient) and ticagrelor (Brilinta) are drugs that inhibit the function of platelets, small blood particles that are involved in blood clotting. Platelet dysfunction and other blood clotting problems have been suspected to play a role in triggering migraines, but the scientific evidence has been lacking.

A report by a cardiologist Dr. Robert Sommer and his colleagues at the Columbia University Medical Center suggests that platelets do contribute to migraines in some patients. They reviewed records of their 136 patients (86% female, mean age 38 years, with an average of 15 headache days a month). Migraines improved on clopidogrel in 80 (59%). The clopidogrel was equally beneficial in patients with episodic and chronic migraines, with and without aura. When the researchers tested platelets in non-responders, 19 of 45 (40%) did not have their platelets inhibited by clopidogrel. Sixteen of those patients were switched to prasugrel, which adequately inhibited platelets and 10 of 16 (62%) had improvement in their migraines. 56 of 90 responders had their PFO closed and the drug stopped after 3 months, which is typically done after a PFO closure. Ninety-four percent had ongoing migraine relief. All 8 of 8 responders who stopped their medication without PFO closure had worsening of their migraines.

This was not a blinded study, so it is premature to recommend PFO closure to migraine patients. However, it can be argued that patients whose migraines do not respond to several drugs, Botox, and monoclonal antibodies should have an echocardiogram to look for a PFO and if one is found, at least given a trial of an antiplatelet medication.