Cluster headaches | Headache NewsBlog

In a new study prednisone relieves cluster headaches

By: Dr. Mauskop

01-02-2021

Blocks, Cluster headaches, Headache medications

Cluster headaches are considered to cause the most severe pain of any type of headache. Once the cluster period begins, headaches occur once or several times a day with each attack lasting 1-3 hours. We do have a new preventive treatment for cluster headaches – monthly injections of a drug that was first approved for migraines, galcanezumab (Emgality). This drug, however, does not help everyone. Even when it does, it can take up to a week to begin helping.

For quick relief, we continue to use a 10-14 day tapering course of steroid medicine, prednisone. Prednisone often works only while the patient is taking it. It is a powerful drug with many potential side effects. This is why it is mostly used for a short time to serve as a bridge that allows another preventive drug to begin working. The most popular preventive medicine for cluster headaches besides Emgality is a blood pressure drug, verapamil.

German researchers just published the results of a double-blind controlled study of prednisone for cluster headaches. They started half of the 116 patients with cluster headaches on placebo and the other half, on 100 mg of prednisone. After five days on 100 mg, they reduced the dose by 20 mg every 3 days. At the same time, all patients were started on verapamil.

In the first week, those on prednisone had a mean of 7.1 attacks, while those on placebo had 9.5 attacks. Statistically, this was a highly significant difference. Having 2-3 fewer attacks in a week may not seem that significant, but only to those who’ve never had a cluster headache. And these mean numbers hide the fact that for some prednisone is highly effective, while for others, not at all. Also, the pain intensity was lower and the number of attacks in the prednisone group remained lower during the fourth week.

Clusters tend to occur once or twice a year or once every few years. Once we find a treatment that works well, including prednisone, it tends to work well for every subsequent attack

No serious side effects occurred in the prednisone group. However, this was a relatively small study and we know that serious side effects can happen even from a short course of prednisone.

About a quarter of my patients get very good immediate relief from an occipital nerve block and avoid taking prednisone. Some of these patients don’t even need Emgality or verapamil. They stay headache-free until the next cluster period.

Even when a preventive treatment is very effective, occasional attacks may still occur. This is why I also always prescribe treatment to stop an individual attack. This is usually sumatriptan injections and occasionally, zolmitriptan nasal spray or inhalation of oxygen.

First drug approved for the prevention of cluster headaches

By: Dr. Mauskop

05-06-2019

Cluster headaches, Headache medications, New treatments

Galcanezumab (Emgality) was just approved by the FDA for the prevention of episodic cluster headaches. Galcanezumab is one of the three new drugs recently approved for the prevention of migraines (the other two are erenumab, or Aimovig and fremanezumab, or Ajovy). These are monoclonal antibodies (mAbs) that block CGRP, a chemical released during attacks of migraine and cluster headaches.

The manufacturer of fremanezumab also conducted trials for the prevention of cluster headaches, but could not prove that the drug was more effective than placebo. Galcanezumab was also tested for chronic cluster headaches and it did not seem to help. Only 10-15% of cluster headache sufferers have the chronic form. About 250,000 Americans suffer from cluster headaches. Compared to migraines, which affect over 35 million Americans, this is a rare disease. This makes it difficult to conduct clinical trials of new treatments. The only abortive drug approved for the treatment of an acute cluster attack is sumatriptan (Imitrex) injection.

The dose of galcanezumab for the prevention of migraines is 240 mg injection at the start and then, 120 mg every month. The dose for cluster headaches is 300 mg. Of the 106 patients in the cluster headache study only 2 stopped the drug because of side effects. Just like in migraine trials, which involved thousand of patients, the only side effect which occur in more than 2% of patients was injection site reactions, but serious allergic reaction can also occur.

Since erenumab was approved for migraines before the other two mAbs and because preliminary evidence suggested that these drugs may work for cluster headaches, we’ve tried erenumab and then, fremanezumab in our cluster patients who did not respond to usual therapy. Although our numbers are too small to make any sweeping conclusions, it appears that just like with migraines, two out of three patients obtain some benefit. Now that galcanezumab is officially approved, we will be using it for all of our cluster headache patients since insurance companies will have to pay for it. Based on our experience with these drugs in migraines, it is likely that the insurers will require that patients first try and fail some of the other preventive therapies, even if none of those have been approved by the FDA. The most commonly used drug for the prevention of cluster headaches is a blood pressure medicine in the calcium blocker family, verapamil. We also try to abort the entire cluster with an occipital nerve block or a course of prednisone, a steroid medication. Epilepsy drugs such as topiramate (Topamax) and a psychiatric drug, lithium can also help.

Cluster headaches affect more men than women and cause more severe pain than migraines, leading some to call them suicide headaches. Women do suffer from cluster headaches as well and they are more often misdiagnosed. Unfortunately men don’t fare well either – 46% of men are misdiagnosed, compared with 61% of women. It takes 5-6 years before the correct diagnosis is made. Cluster headaches are often mistaken for migraines because pain is on one side of the head and for sinus headaches because cluster headaches are usually accompanied by a runny nose.

This is a cluster season, again

By: Dr. Mauskop

12-04-2019

Cluster headaches

Cluster headaches derive their name from the fact that they occur daily for a period of one to several months. It is rarely noted that these cluster periods occur in many patients at the same time. We do not see any cluster patients for several months and then, we see them daily for a couple of months and now is such a period. It is not clear what environmental factors may be playing a role. These periods when cluster patients start having their attacks do not appear to be related to barometric pressure changes, high allergy seasons, pollution, or any other factors. In some patients attacks occur always in the same season and even the same month, but in many a cluster period can start at any time.

Cluster headaches often cause extremely severe pain, which is always on one side and rarely switch sides from one cluster period to the next. The pain is accompanied by nasal congestion, runny nose and tearing on the side of the headache. Unlike migraine patients who prefer to lie down in a dark and quiet place and not move, patients with cluster headaches become agitated and cannot sit still. The attacks occur once or several times a day, often at the same time of day or night and last anywhere from 15 minutes to a couple of hours. Cluster headaches occur at least twice as often in men than in women and this is probably why cluster headaches are often misdiagnosed in women.

A recent review confirmed that cluster headaches respond well to inhalation of oxygen. The only FDA-approved treatment for the treatment of cluster headaches is injection of sumatriptan to treat each attack. To stop the entire cluster we give occipital nerve blocks and prescribe short courses of prednisone (corticosteroid). If headaches persist, a blood pressure medication, verapamil can be effective if given in high doses. The new migraine drugs, CGRP monoclonal antibodies (Aimovig, Ajovy, and Emgality), appear to be very effective for some patients with cluster headaches, although they are not yet FDA-approved for this type of headaches.

A very promising new treatment for cluster headaches

By: Dr. Mauskop

21-05-2018

Cluster headaches, Headache medications

A new and very promising preventive treatment for cluster headaches being developed by Eli Lilly may become available in the near future. We hope that the FDA recognizes that this is a relatively rare condition with few available treatments and will not require extensive clinical trials, especially because the safety of this drug has been demonstrated in a large number of migraine patients.

CGRP monoclonal antibodies are very effective for the prevention of migraines and four companies are developing such drug. Thankfully, one of these companies, Eli Lilly decided to study this type of treatment for cluster headaches. The company just announced the results of a phase 3 trial in 106 patients that showed their product, galcanezumab to be effective in preventing episodic cluster headaches. The drug did not help prevent attacks in patients with chronic cluster headaches, which constitute 10-15% of cluster patients.

Last week, the first CGRP monoclonal antibody, erenumab (Aimovig) was approved for the preventive treatment of migraine headaches. Considering that all four CGRP drugs are similar, it is possible that erenumab is also effective for cluster headaches. However, because it was not studied for this indication and has no FDA-approval, insurance companies are not likely to pay for it. On the other hand, cluster attacks last one to three months, so the cost is less prohibitive than it is for the long-term treatment of migraines and patients are more desperate to find relief at any cost.

Cluster headaches affect less than 0.5% of the population (mostly men), but they are often excruciating and sometimes described as suicidal. The name cluster comes from the fact that these headaches occur daily for a month or two and then go away for a year. Chronic cluster headaches continue to occur for more than a year without a break. Each attack lasts anywhere from 15 minutes to a couple of hours, often waking the patient from sleep, usually at the same time of night. The pain is always on one side, around the eye and sometimes at the back of the head. Besides pain, patients experience tearing and nasal congestion on the side of the headache. Unlike with migraine, where patients try to lie quietly and not move, cluster attacks lead to agitation, restlessness, pacing and even hitting the head with a fist or against a hard object.

The only FDA-approved treatment for cluster headaches is injection of sumatriptan (Imitrex, Imigran) to abort each individual attack. This drug is also approved for migraines, indicating that there are similarities between these conditions. Other abortive treatments included inhalation of oxygen and intranasal zolmitriptan (Zomig NS), while tablets tend to be too slow to work. For prevention, we use occipital nerve blocks, a course of steroids or daily drugs, such as verapamil (Calan).

Most of these older treatments work for about 50% of patients, so it is very exciting to have a highly effective treatment that was specifically developed for cluster headaches.

Breakthrough in the treatment of migraines

By: Dr. Mauskop

08-12-2017

Cluster headaches, injections, Migraine, New treatments

Two landmark studies on an entirely new type of treatment for migraines have been just published in the New England Journal of Medicine.

One of the reports describes a phase 3 trial (final phase that can lead to the FDA approval), which was conducted by Teva Pharmaceuticals using a monoclonal antibody, fremanezumab to treat patients with chronic migraine (patients with 15 or more headache days each month). The study involved 1,130 patients who were divided into three groups: one group received monthly injections (subcutaneously, i.e. under the skin) of the active medicine, another group was given an injection of the real medicine every 3 months and placebo injections monthly in between, and the third group received placebo injections every month. Patients in both groups that received real shots did much better than those given placebo. They had fewer days with headaches, used less of the abortive migraine medications, and had a lower impact of migraines on their lives. The effect of the drug lasted 3 months, which suggests that one injection every three months will be sufficient. We also hope that patients will be able to inject themselves and not have to come to doctors’ offices every month. The side effects were mostly related to the injection itself – pain, swelling, and bruising.

The second study conducted by Amgen and Novartis utilized a similar drug, erenumab (it will have the brand name of Aimovig when it becomes available in the middle of next year) to prevent episodic migraines, that is migraines that occur on fewer than 15 headache days each month. A total of 955 patients participated in this study and they were also divided into three groups: those receiving either 70 or 140 mg of medicine and a group receiving placebo. Injections were given monthly to prevent migraine attacks. Both doses of the drug resulted in significantly fewer migraine attacks and improvement in physical impairment and everyday activities. Side effects were mostly due to the injection site reactions, just like with fremanezumab.

Both fremanezumab and erenumab belong to the family of CGRP monoclonal antibodies, drugs that block a neurotransmitter CGRP which is released during a migraine attack. Two additional companies, Eli Lilly and Alder are developing similar drugs, galcanezumab and eptinezumab, which are also expected to be approved next year. Eli Lilly’s drug is also being tested for the prevention of episodic cluster headaches.

I first wrote about the CGRP drugs in a blog post in 2007, more than 10 years ago. At that point CGRP was the target of research for over 10 years, so in total, it will have taken 20 years to bring these new drugs to the market. It was even longer with triptans, such as sumatriptan (Imitrex) – it took 30 years since the discovery of the potential role of serotonin to the approval of sumatriptan. The drug development process takes not only decades of time, but also billions of dollars, which explains why new drugs are so expensive, at least in the first few years. After years of being on the market, prices of drugs tend to go down and now 90 tablets of sumatriptan can be bought for $70 at Costco, while similar branded triptan drugs used to cost $40 for a single tablet.

What to do when Botox stops working

By: Dr. Mauskop

07-10-2017

Botox, Chronic migraine, Cluster headaches, Migraine

Botox is the most effective and the safest preventive treatment for migraine headaches. However, in a very small number of patients, Botox loses its effectiveness over time. This happens for two main reasons – the person develops antibodies as a defense mechanism to block the effect of Botox or headaches change in character and stop responding to Botox.

It is easy to tell these two reasons apart. If Botox fails to stop movement of the forehead muscles and the patient can frown and raise her eyebrows, it is most likely because of antibodies. On a very rare occasion this is due to a defective vial of Botox, so to confirm that antibodies have formed, we give a small test dose amount of Botox into the forehead. If again there is no paralysis, we know that antibodies have developed. This can happen after one or two treatments or after 10, but in my experience over the past 25 years, significantly fewer than 1% of patients develop this problem.

Fortunately, some patients who develop antibodies to Botox, known as type A toxin, may respond to a similar product Myobloc, which is a type B toxin. Myobloc is not approved by the FDA to treat chronic migraine headaches, but it has a similar mechanism of action and has been shown to relieve migraines in several studies. Injections of Myobloc can be a little more painful, it begins to work a little faster than Botox, but the effect may last for a slightly shorter period of time.

An even smaller number of patients have naturally occurring antibodies to Botox, which is most likely due to an exposure to botulinum toxin in food. I’ve encountered 4 or 5 such patients and a couple of them who did go on to try Myobloc, did not respond to it either.

When Botox stops working despite providing good muscle relaxing effect, it could be because the headaches have changed in character, severity or are being caused by a new problem. It could be due a sudden increase in stress level, lack of sleep, hormonal changes, drop in magnesium level due to a gastro-intestinal problem, or another new illness, such as thyroid disease, diabetes, multiple sclerosis, or increased pressure in the brain. Such patients need to be re-evaluated with a neurological examination, blood tests, and usually an MRI scan. One of my patients who was doing well on Botox for several years, did not have any relief from her last regular treatment. Since she had no obvious reasons why her migraines should stop responding to Botox, I ordered an MRI scan. Unfortunately, she turned out to have brain metastases from breast cancer which had not yet been diagnosed.

New information on cluster headaches

By: Dr. Mauskop

17-07-2017

Blocks, Botox, Cluster headaches, Headache medications

Cluster headache is one of the most painful conditions that has lead some patients call it a suicide headache. A new observational study done by researchers at the Eli Lilly company and Stanford University was presented at the recent annual scientific meeting of the American Headache Society.

Considering that cluster headaches are relatively rare, the major strength of this study is its size – 7589 patients. These patients were compared to over 30,000 control subjects without headaches. We’ve always known that cluster headaches are more common in men with previous studies indicating that male to female ratio is between 5:1 and 3:1. However, only 57% of patients in this new report were males. This does not reflect my experience – I see at least five times as many men as women. It is possible that I underdiagnose cluster headaches in women or the study used unreliable data. In fact, the study data was collected from insurance claims, so I suspect that the truth is closer to my experience and to the older published data.

The study did find that thoughts of suicide were 2.5 times more common in patients with cluster headaches compared to controls, while depression, anxiety and sleep disorders were twice as common. Cluster headache patients also were 3 times more likely to have drug dependence. The most commonly prescribed drugs were opiates (narcotics) in 41%, which partially explains high drug dependence rates, steroids, such as prednisone (34%), triptans, such as sumatriptan (32%), antidepressants (31%), NSAIDs (29%), epilepsy drugs (28%), blood pressure drugs, such as verapamil (27%), and benzodiazepines, such as Valium or Xanax (22%).

It is very unfortunate that over a period of one year only 30% of patients were prescribed drugs recommended for cluster headaches. We know that narcotics and benzodiazepine tranquilizers are not very effective and can lead to dependence and addiction. Drugs that are effective include a short course of steroids (prednisone), sumatriptan injections, blood pressure drug verapamil (often at a high dose), some epilepsy drugs and occasionally certain antidepressants. The report did not mention oxygen, which can stop individual attacks in up to 60% of cluster headache sufferers. Nerve blocks and to a lesser extent, Botox injections can also provide lasting relief. It is possible that the data on oxygen, nerve blocks and Botox was not available.

Cluster headaches are more often misdiagnosed in women

By: Dr. Mauskop

13-03-2017

Cluster headaches

Cluster headaches are much less common than migraines (less than a million vs 36 million sufferers), but are arguably the most painful type of headaches a man can experience. And it is usually a man because cluster headaches are thought to be 3-5 times more common in men. However, a study just published in Neurology suggests that the ratio of men to women is closer to 2:1.

This study by Danish researchers also established that women suffering from cluster headaches are more often misdiagnosed than men – 61% vs 46%. Consequently, it takes a year longer for a woman to be diagnosed than for a man – 6.5 years vs 5.5 years. But considering how devastating these headaches can be, these numbers are terrible for both sexes.

Cluster headaches get their name from the fact that they occur in clusters – daily or more frequent attacks lasting one to three hours for a period of a month or two, each year and often at the same time of year. One surprising finding of the study is that women are more likely to have chronic cluster headaches (no break from attacks for more than a month) – 44% vs 32%.

The reason for such high rates of misdiagnosis and long delays in diagnosing cluster headaches is that it is a relatively rare type of headaches and that it is easy to mistake cluster for a migraine or a sinus headache. Cluster headache is always one-sided and centers in the eye, which is common with migraines. It is usually accompanied by a runny nose (and tearing with redness of the eye) as occurs with a sinus headache.

But cluster headaches also have very distinctive features that should make the diagnosis easy, if only doctors asked a few questions. I’ve had a fair number of patients who diagnosed themselves after being misdiagnosed by doctors. During a cluster attack patients tend to be restless, pacing around, hitting their fist or even their head against walls, and sometimes screaming from pain, while migraine sufferers tend to stay very quiet since every movement, sound, and light worsen the pain. The fact that these occur every night for an hour or two and then resolve on their own is also a telltale sign. Migraine pain lasts for at least 4 hours and often for a couple of days without a break. Sinus headaches do not come and go and are easy to rule out by a CAT scan, a standard equipment in every emergency room and cluster sufferers do often end up in an ER.

Fortunately, once the correct diagnosis is made, cluster headaches can be treated very effectively in most patients. Some of the treatments overlap with migraines, such as sumatriptan injections, magnesium infusions, occipital nerve blocks, and Botox injections, but other help only cluster headaches. These include a 10-day high-dose course of steroids, oxygen inhalation, high-dose verapamil, lithium, and other.

Cluster headaches, sleep disturbance, and depression

By: Dr. Mauskop

09-11-2016

Cluster headaches

According to large epidemiological studies, migraine sufferers are 2-3 times more likely to develop depression, anxiety and other psychiatric disorders than those without migraines. And it is a bidirectional relationship, meaning that those with depression are 2-3 times more likely to develop migraines than those without depression. Cluster headaches, which have at times been referred to as “suicide headaches,” have been suspected to be also associated with depression. Until now, no similar large studies have been conducted in patients with cluster headaches in part because cluster headaches are much less common than migraines.

In a study just published in the journal Neurology, a group of Dutch physicians studied 462 patients with cluster headaches and compared them to 177 control subjects. They evaluated these patients for history of depression during their lifetime, current depression in the midst of a cluster period, and because many cluster attacks occur in sleep, they also looked for sleep disturbances. The results showed that depression was 3 times more likely to occur patients with cluster headaches than in healthy controls. Those with chronic cluster headaches had a higher risk of depression and sleep problems than patients with episodic cluster headaches. Current depression was associated with having active attacks within the preceding month, but this association was only present if the patient also had a sleep disturbance.

The authors concluded that cluster headache patients are three times more likely to develop depression in their life time. However, current depression was in part related to sleep disturbances due to ongoing nocturnal cluster attacks.

Daily long-term use of sumatriptan injections in cluster headaches

By: Dr. Mauskop

07-02-2016

Cluster headaches, Headache medications, injections

My most commented on blog post (over 150 comments) is on the daily use of triptans. A new report confirms the safety of long-term daily use of sumatriptan injections in cluster patients. Cluster headaches are arguably the most severe type of headaches and the name comes from the fact that they tend to occur in clusters lasting several weeks to several months. However, in some patients headaches become persistent without any remissions and then they are called chronic cluster headaches. The only FDA approved treatment for cluster headaches is injectable sumatriptan (Imitrex). Most patients have one cluster attack in 24 hours, but some have many. A report mentioned in one of my other previous blogs describes a woman (although men are more commonly affected by cluster headaches) who has been injecting sumatriptan daily on average 20 times a day for 15 years.

A recent report by Massimo Leone and Alberto Cecchini is entitled, Long-term use of daily sumatriptan injections in severe drug-resistant chronic cluster headache.

The authors investigated occurrence of serious side effects in patients with chronic cluster headaches who were using sumatriptan injections continuously at least twice daily (the official limit) for at least 2 years. They found fifty three such patients with chronic cluster headaches seen in their clinic between 2003 and 2014. During the 2-year period, all patients were carefully followed with regular visits at their center. Headaches and sumatriptan consumption were recorded in headache diaries. Patients were questioned at each visit about serious side effects and had at least two electrocardiograms. Brain MRI was normal in all patients. None of the patients had a history of stroke, TIA, ischemic heart disease, myocardial infarction, or arrhythmia, or diseases affecting systemic vessels.

In the 2-year study period, no serious side effects were observed and no patients needed to discontinue sumatriptan use. No electrocardiogram abnormalities were found. All patients needed a full dose (6 mg) of sumatriptan injection (prefilled syringes with 4 and 6 mg available). At the end of the study period, 42% noticed some reduction in the efficacy of sumatriptan injections both in terms of time of onset of effect and on pain intensity, but still considered the drug their first choice to treat the attacks.

In the study period, 36 of the 52 patients (69%) used more than 12 mg of sumatriptan in 24 hours (maximum 36 mg in 24 hours) but no increase in number or severity of side effects was observed during the course of the study. Complete loss of efficacy was not reported by any of the patients.

The authors mention that since the launch of sumatriptan injections in 1992 and until 1998, approximately 451 serious cardiac side effects have been reported to occur within 24 hours after administration of sumatriptan injections, tablets or nasal spray, but this is out of more than 236 million migraine attacks and more than 9 million patient exposures between 1992 and 1998. The majority of patients who developed serious cardiac events within 1 to 3 hours of sumatriptan administration had risk factors for coronary artery disease.

The authors concluded that their results showed that long-term daily sumatriptan use in patients free of heart disease did not cause serious side effects and this is in line with observations from previous studies.

Cluster headaches are on an upsurge in the past 2 weeks. Is sun to blame?

By: Dr. Mauskop

13-10-2015

Cluster headaches

Solar activity is high again – NASA’s Solar Dynamics Observatory reported a flare on October 1. And in the past two weeks we’ve been seeing many more patients whose cluster headaches returned. The last time we had a surge in the number of cluster patients was last October, when solar activity was also high (see this post).

Unfortunately, there is not a lot we can do about the solar activity, but we do have many treatment options for cluster headaches. These include intravenous magnesium (40% of cluster headache sufferers are deficient), occipital nerve blocks, steroids, daily prevention with verapamil, Botox injections, oxygen inhallation, nasal spray of zolmitriptan (Zomig NS), and sumatriptan (Imitrex) injections. For most cluster patients one more often several of these treatments provide good relief. If these are ineffective, we also use drugs such as lithium, topiramate, and even an herbal supplement, Boswellia.

Testosterone and headaches

By: Dr. Mauskop

07-08-2015

Chronic migraine, Cluster headaches, New treatments

Fluctuations in the female hormone estrogen have been proven to be involved in triggering menstrual and perimenopausal migraine headaches. Testosterone levels have been reported to be low in men and women with cluster headaches. Testosterone replacement therapy seems to help these patients, when other standard treatments for cluster headaches do not.

A study presented at the recent annual meeting of the American Headache Society reported on testosterone levels in men with chronic migraine headaches. A significant percentage of men with chronic migraines also have low testosterone levels. This study did not look at the effect of testosterone replacement therapy, but it is possible that it may help chronic migraine sufferers as it does those with cluster headaches. It seems prudent to check testosterone level in men with chronic migraine headaches who do not respond to standard approaches such as medications, Botox injections, magnesium, and other treatments. And if the level is low, replacement therapy should be tried.