Research Activities, March 2014
Little difference in effectiveness of drugs to prevent episodic migraine in adults
All four drugs approved by the U.S. Food and Drug Administration for prevention of adult episodic migraine (the anti-epileptics, divalproex and topiramate, and the beta-blockers, timolol and propranolol) were found effective in a review of studies on the medications. These drugs were found to be better than placebo in reducing monthly migraine frequency by at least 50 percent in 200–400 patients per 1,000 treated, according to a the review of 215 randomized controlled trials (RCTs) and 76 nonrandomized studies. However, none of the approved drugs was found to be significantly more beneficial than the others.
Migraine headaches affect 17 percent of women and 6 percent of men in the United States and fall into two classes—episodic migraines, defined as lasting less than 15 days per month, and chronic migraines that last at least 15 days per month for at least 3 months. Even episodic migraines can cause serious lifestyle limitations, requiring preventive medication. In addition to studies of the approved drugs, single RCTs found that the off-label beta-blockers acebutolol, atenolol, and nadolol had comparable effectiveness—as did the angiotensin-inhibiting drugs captopril, lisinopril, and candesartan, according to the researchers.
Further indirect comparison suggested that the off-label angiotensin-inhibiting drug candesartan was more likely to produce an effective response than any of the approved drugs. Also, among the off-label drug classes, angiotensin-inhibiting drugs were nearly three times more likely to be effective than antidepressants or off-label anti-epileptics, and nearly four times more likely to be effective than ergot alkaloids.
From the 159 RCTs reporting adverse effects for the drugs tested, the approved drugs topiramate and propranolol produced adverse effects leading to treatment discontinuance more often than placebo, as did the antidepressant amitriptyline. Indirect network meta-analysis suggested that off-label beta-blockers and off-label angiotensin-inhibiting drugs were least likely to result in adverse effects leading to discontinuing treatment. The study was funded in part by AHRQ (Contract No. 290-01-0012).
More details are in "Preventive pharmacologic treatments for episodic migraine in adults," by Tatyana A. Shamiliyan, M.D., M.S., Jae-Young Choi, Ph.D., Rema Ramakrishnan, M.P.H., and others in the September 2013 Journal of General Internal Medicine 28(9), pp. 1225-1237.