An Option for Migraine Prevention?
Medscape Medical News
June 2, 2014
By Hans-Christoph Diener, MD, PhD, neurologist from the University Hospital in Essen in Germany.
Patients who have frequent migraine attacks are not supposed to treat these with increasing numbers of pain medications or migraine drugs such as triptans because these drugs can lead to medication-overuse headache.
In these patients, we need preventive therapy. Preventive therapy has 2 components. One is nonmedical treatment with exercise, sports, behavioral therapy, and stress management. The other is drug therapy, and the approved drugs are propranolol, flunarizine, valproic acid, topiramate, and amitriptyline. With the exception of topiramate, all of these drugs will lead to weight gain, which is not very popular with most of our female migraine patients. This is why we need alternatives.
A group from Norway had reported a few years ago in a small phase 2 trial that they observed the positive effect of candesartan on migraine frequency compared with placebo.[1] The same group has now completed another trial, which was a 3-phase crossover trial.[2] They compared 16 mg of candesartan with 160 mg of slow-release propranolol and placebo. Treatment phases lasted 12 weeks, followed by a washout period of 4 weeks. Patients would then use the next treatment. This was a very complicated design, but they managed to do it. The primary endpoint was reduction in migraine data. They originally had 72 patients who participated in the study. Most were women, and the average age was 37 years.
At the end of the study, there was a significant benefit from both candesartan and propranolol compared with placebo for migraine headaches. This is best reported in the so-called "responder rates." Responders are people who have at least 50% reduction in migraine frequency. The responder rate was 23% for placebo, which is a typical responder rate. It was 43% for candesartan and 40% for propranolol. There was no difference between the 2 active treatments, but there was a significant benefit compared with placebo.
Side effects were mild and usually did not lead to termination of treatments. The most frequent side effects of candesartan were dizziness and tiredness. Propranolol had similar side effects as well as causing weight gain.
It seems that the sartans -- in particular, candesartan -- might be effective in migraine prevention. These drugs are usually very well-tolerated. The downside is that these drugs are not officially approved for the prevention of migraine. At present, it's an off-label treatment.
This is an important new development in migraine prevention.
Source MedicineNet.com
Candesartan cilexetil (candesartan) is a drug used for treating high blood pressure (hypertension). It is in a class of drugs called angiotensin receptor blockers (ARBs) which includes losartan (Cozaar), valsartan (Diovan), and irbesartan (Avapro). Angiotensin, formed in the blood by the action of angiotensin converting enzyme (ACE), is a powerful chemical that attaches to angiotensin receptors found in many tissues but primarily on smooth muscle cells surrounding blood vessels. Angiotensin's attachment to the receptors causes the muscle cells to contract and the blood vessels to narrow (vasoconstrict) which leads to an increase in blood pressure . Candesartan blocks the angiotensin receptor and therby prevents the action of angiotensin. As a result blood vessels expand and blood pressure is reduced. Candesartan was approved by the FDA in 1998.
* Also available in Canada
Complete JAMA article attached
Medscape Medical News
June 2, 2014
By Hans-Christoph Diener, MD, PhD, neurologist from the University Hospital in Essen in Germany.
Patients who have frequent migraine attacks are not supposed to treat these with increasing numbers of pain medications or migraine drugs such as triptans because these drugs can lead to medication-overuse headache.
In these patients, we need preventive therapy. Preventive therapy has 2 components. One is nonmedical treatment with exercise, sports, behavioral therapy, and stress management. The other is drug therapy, and the approved drugs are propranolol, flunarizine, valproic acid, topiramate, and amitriptyline. With the exception of topiramate, all of these drugs will lead to weight gain, which is not very popular with most of our female migraine patients. This is why we need alternatives.
A group from Norway had reported a few years ago in a small phase 2 trial that they observed the positive effect of candesartan on migraine frequency compared with placebo.[1] The same group has now completed another trial, which was a 3-phase crossover trial.[2] They compared 16 mg of candesartan with 160 mg of slow-release propranolol and placebo. Treatment phases lasted 12 weeks, followed by a washout period of 4 weeks. Patients would then use the next treatment. This was a very complicated design, but they managed to do it. The primary endpoint was reduction in migraine data. They originally had 72 patients who participated in the study. Most were women, and the average age was 37 years.
At the end of the study, there was a significant benefit from both candesartan and propranolol compared with placebo for migraine headaches. This is best reported in the so-called "responder rates." Responders are people who have at least 50% reduction in migraine frequency. The responder rate was 23% for placebo, which is a typical responder rate. It was 43% for candesartan and 40% for propranolol. There was no difference between the 2 active treatments, but there was a significant benefit compared with placebo.
Side effects were mild and usually did not lead to termination of treatments. The most frequent side effects of candesartan were dizziness and tiredness. Propranolol had similar side effects as well as causing weight gain.
It seems that the sartans -- in particular, candesartan -- might be effective in migraine prevention. These drugs are usually very well-tolerated. The downside is that these drugs are not officially approved for the prevention of migraine. At present, it's an off-label treatment.
This is an important new development in migraine prevention.
Source MedicineNet.com
Candesartan cilexetil (candesartan) is a drug used for treating high blood pressure (hypertension). It is in a class of drugs called angiotensin receptor blockers (ARBs) which includes losartan (Cozaar), valsartan (Diovan), and irbesartan (Avapro). Angiotensin, formed in the blood by the action of angiotensin converting enzyme (ACE), is a powerful chemical that attaches to angiotensin receptors found in many tissues but primarily on smooth muscle cells surrounding blood vessels. Angiotensin's attachment to the receptors causes the muscle cells to contract and the blood vessels to narrow (vasoconstrict) which leads to an increase in blood pressure . Candesartan blocks the angiotensin receptor and therby prevents the action of angiotensin. As a result blood vessels expand and blood pressure is reduced. Candesartan was approved by the FDA in 1998.
* Also available in Canada
Complete JAMA article attached
