Updated 04 July 2014

Migraine prevention comes at a cost

People with severe or frequent migraines often turn to medication to prevent these. But do the medications work?


A new review of preventive treatments shows there is not much difference in the effectiveness of commonly prescribed drugs they work for some people, in some cases. But there is wide variation in the amount and severity of side effects associated with the drugs.

The researchers found that drugs worked better than inactive placebos in reducing monthly migraine attacks. They prevented half or more migraines in 200 to 400 people per 1 000 treated. But many of the medications had side effects so bothersome that sufferers frequently stopped taking them.

That could be because none of the drugs used to prevent migraines was designed specifically for that purpose, explained Dr. Jason Rosenberg, director of the Johns Hopkins Headache Center. "So, it's not surprising that they don't work all that well. Only one-third get halfway better, according to the study, so a doctor has to treat three people to get one patient better."

Doctors not aware of the side-effects

Rosenberg, who was not involved with the study, suffers from migraines and thinks many primary care doctors may be less aware of the side effects of the drugs used to prevent migraines than are headache specialists. So, they may not warn patients about the potential problems and frequently don't follow up to see how the patients are doing, he added.

The side effects are typically no fun, said Rosenberg. "A number are badly tolerated. Some cause weight gain, hair loss, can cause birth defects [one drug], some tingling, sleepiness, impaired ability to exercise, an increased risk of diabetes and sexual side effects," he noted. Some problems, such as kidney stones, are only detected with long-term follow-up, he added.

That's why physicians and patients need better information, said review author Dr. Tatyana Shamliyan, a researcher at the Minnesota Evidence-Based Practice Center in Minneapolis. Good research clearly shows potential benefits and harms, and "helps a great deal in making informed decisions," she said.

But finding information about the options and downsides can be difficult.

Rosenberg said that before Shamliyan's study, no one had done a thorough, comprehensive review of the side effects of medications used to prevent migraines. "They've done a Herculean task," he said.

Both the American Academy of Neurology and the American Headache Society have issued guidelines that recommend two types of anti-epileptic drugs and two beta blockers for prevention of migraines in adults. But neither medical group considered the value of balancing the effectiveness against the side effects, Shamliyan said.

Migraines affect about 12% of the US population, and involve throbbing or pulsing head pain, often associated with sensitivity to light and sound, according to the US National Library of Medicine.

The new research was published online in the April issue of the Journal of General Internal Medicine. Out of an initial group of more than 5 000 studies related to preventing migraines, the researchers found 215 publications that involved randomised clinical trials considered the gold standard in research  and 76 publications of non-randomised studies. The researchers reported that most trials were funded by industry and did not disclose conflicts of interest by study investigators.

Most of the studies were conducted in the United States and Western countries, and enrolled mostly middle-aged women with episodic migraines. Participants were mostly overweight and had an average of five migraine attacks a month. Shamliyan noted that many of the studies failed to control for key factors, such as the severity of the headaches, the presence of other health conditions in those studied, other migraine treatments being used, family history, and social and economic status.

Approved drugs effective

Based on their analysis of the studies, the researchers concluded that approved drugs and off-label angiotensin-inhibiting drugs (lisinopril, captopril and candesartan), or off-label beta blockers (metoprolol, acebutolol, atenolol and nadolol) were effective in preventing episodic migraines in adults.

Off-label angiotensin-inhibiting drugs showed the most favorable combination of benefits to potential harms. The US Food and Drug Administration permits physicians to prescribe approved medications for purposes other than their intended indications, and that practice is known as off-label use.

The study also found that there's a lack of research available about the long-term effects of drug treatments, especially on quality of life.

In treating migraines, off-label medications are frequently used, said Rosenberg. "In my practice I'm prescribing off-label as much as on-label." This, while state-of-the-art, should be a call to action, he added. "It's totally unacceptable that all the drugs we're using were invented for other diseases."

More information

Learn more about migraines from the U.S. National Library of Medicine.

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Headache expert

Dr Elliot Shevel is a South African migraine surgery pioneer and the founder and medical director of The Headache Clinic in Johannesburg, Durban and Cape Town, South Africa. The Headache Clinic is a multidisciplinary practice dedicated to the diagnosis and treatment of Primary Headaches and Migraines. Dr Shevel is also the main author of all scientific publications generated by his team. He recently won a high level science debate in which he was able to prove that the current migraine diagnosis and classification is not based on data. Tertiary Education - Dr Shevel holds both Dental and Medical degrees, and practises as a specialist Maxillo-facial and Oral Surgeon. Follow the Headache Clinic on Twitter@HeadacheClinic.

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