Be Aware of Taking Verapamil for Cluster Headaches, it May Cause Arrhythmia
Migraine is an episodic headache that is unilateral or bilateral, pulsating in quality, moderate to severe in intensity, and exacerbated by physical activity. Associated symptoms include nausea or vomiting, photophobia, and phonophobia. The disorder is classified as migraine with aura (previously called classic migraine) and migraine without aura (previously called common migraine), according to the presence or absence, respectively, of premonitory neurologic symptoms.
Cluster headaches and migraine have many similarities but also many differences. In contrast to migraine, cluster headaches are more prevalent in men, are not preceded by an aura, always occur unilaterally with pain recurring on the same side in subsequent headaches, and usually are not associated with a positive family history of cluster headache.
Cluster headache is the most severe form of primary headache.The chronic form, sometimes called chronic migrainous neuralgia, which may begin de novo or several years after an episodic pattern has become established, is characterized by the absence of sustained periods of remission. Each type may transform into the other. The cluster syndrome is genetically, biochemically, and clinically different from migraine; propranolol is effective in treating migraine but has not been shown to be effective in cluster headache.
Cluster headaches may also be known as histamine headache, red migraine, Horton’s headache, and cephalalgia or sphenopalatine neuralgia. The headache periods can last several weeks or months, and then disappear completely for months or years leaving considerable amounts of pain-free intervals between series.
The pain has been described as feeling "like the eye is going to explode." They've caused their victims to pace the floor in agony, unable to lie down; literally bang their heads against a wall; even, on rare occasions, to commit suicide to escape the pain. They're cluster headaches, and those who suffer from them are often called ClusterHeads.
Prevention of attacks during a cluster cycle is extremely important. Although patients with episodic or chronic cluster headaches may be given different medications.Treatment with a calcium-channel blocker, either nifedipine or verapamil may stop the attacks.
The calcium channel blocking agent verapamil (Calan, Verelan, others) is often the first choice for preventing cluster headache, although the way verapamil works with cluster headache isn't well understood. The medication may be used from the start of a cluster period until three to four weeks after the last headache. Then its use is gradually tapered and discontinued under your doctor's direction. Occasionally, longer term use is needed to manage chronic headache.
Studies have shown that verapamil may be effective in the preventive treatment of migraine and cluster headache patients. In several patients, the attacks of amaurosis fugax resumed when the calcium-channel blocker was discontinued, and then abated again when treatment was resumed.
In two surveys, patients reported a delay in the diagnosis of their headaches of 1 - 6 years. In most of these cases, patients were inappropriately treated for other headaches (including having sinus surgery).
The extreme pain can be markedly diminished within 15 minutes by an under-the-skin injection of sumatriptan (Imitrex®) or by using a sumatriptan nasal spray.Ergotamine (Ergostat®) is particularly effective for preventing attacks that occur at predictable times.
People who use a blood pressure drug called verapamil to treat cluster headaches may be putting their hearts at risk.
That's the finding from a British study that found heart rhythm abnormalities showing up in about one in five patients who took the drug in this unapproved, "off-label" way.
"The good news is, when you stop the drug, the effect wears off," said study lead author Dr. Peter Goadsby, professor of neurology at University College London. "So, as long as doctors know about it, and patients with cluster headaches on verapamil know they need EKGs [electrocardiograms] done, it is a completely preventable problem."
In a review of the medical records of 217 patients given verapamil to treat their cluster headaches, a team led by Goadsby found that 128 had undergone an EKG, 108 of which were available in the medical records.
Of those 108 patients, about one in five exhibited abnormalities (mostly slowing) in the heart's conduction system -- the "natural pacemaker" that causes the organ to beat. Most of these cases weren't deemed serious, although one patient did end up having a pacemaker implanted to help correct the problem. In four cases, doctors took patients off verapamil due to their EKG findings.
One in three (34 percent) developed non-cardiac side effects such as lethargy and constipation.
"It is a very nice piece of work, because it provides commentary on a boutique [that is, niche and off-label] use of the drug," said Dr. Domenic Sica, professor of medicine and pharmacology in the Virginia Commonwealth University Health System. He was not involved in the study.
Cluster headache affects about 69 in every 100,000 people, according to the Worldwide Cluster Headache Support Group Web site. Men are six times more likely than women to be afflicted, and the typical age of onset is around 30. According to Goadsby, the disease manifests as bouts of very severe pain, one or many times per day, for months at a time, usually followed by a period of remission.
Verapamil, a calcium-channel antagonist drug, is approved by the U.S. Food and Drug Administration for the treatment of cardiac arrhythmias and high blood pressure. The medicine is typically given in doses of 180 to 240 milligrams per day to help ease hypertension.
However, the patients in this study received more than twice that dose for the off-label treatment of their cluster headaches -- 512 milligrams per day on average, and one patient elected to take 1,200 milligrams per day. The treatment protocol involved ramping up the dose from 240 milligrams to as high as 960 milligrams per day, in 80 milligram increments every two weeks, based on EKG findings, side effects, and symptomatic relief.
Many patients may not be getting those kinds of tests to monitor heart function, however: In this study cohort, about 40 percent of patients never got an EKG.
Given the typical dosage, Sica said he was surprised so many patients were able to tolerate such high amounts of the drug.
"When used in clinical practice for hypertension, the high-end dose is 480 milligrams," said Sica. "Most people cannot tolerate 480."
Dr. Carl Pepine, chief of cardiology at the University of Florida, Gainesville, was also "amazed" at the doses that were tolerated in this study. "The highest dose I ever gave [for cardiology indications] was 680 milligrams. This might give me more encouragement to use the drug at higher dose," he said.
But Sica said he thought cardiac patients -- the typical verapamil users -- were unlikely to tolerate the drug as well as the patients in this study, because verapamil reacts differently in older individuals, who are more likely to have high blood pressure, than in younger patients. The average patient in the United Kingdom study was 44 years old.
According to Sica, two factors would conspire to make older individuals more sensitive to verapamil. First, the metabolism of the drug is age-dependent, meaning that older individuals would tend to have higher blood levels of the drug, because it is cleared more slowly than in younger individuals.
Secondly, the conduction system of the heart (the natural "pacemaker") becomes more sensitive to the effects of verapamil with age, Sica said.
"It's likely that an older population would not be able to tolerate the same dose," he concluded.
According to Goadsby, the take-home message of this study is simple: Be sure to get regular EKGs if you are taking verapamil for cluster headaches. Goadsby recommended EKGs within two weeks of changing doses, and because problems can arise over time -- even if the dose doesn't change -- to get an EKG every six months while on a constant dose.
"The tests are not expensive, and they are not invasive," he said. "They are not in any way a danger to the patient."
For the most part, Goadsby said, should a cardiac problem arise, it will typically go away once the treatment is halted.
Arrhythmias are disorders of the regular rhythmic beating of the heart. They're common — about 2.2 million Americans are living with atrial fibrillation (one type of rhythm problem). Arrhythmias can occur in a healthy heart and be of minimal consequence.