Cluster headaches: searching for effective therapies

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Thought LeadersDr. Nick SilverConsultant NeurologistThe Walton Centre

An interview with Dr. Nick Silver, Consultant Neurologist, The Walton Centre, conducted by April Cashin-Garbutt, MA (Cantab)

What are cluster headaches and who do they affect?

Cluster headaches are probably the most painful types of pain a human can suffer and it is for no small reason that this condition is also sometimes referred to as suicide headache.

The condition most commonly occurs in bouts referred to as “clusters” which may last some weeks and these may repeat in a seasonal manner.

Cluster headaches are the most common headaches to occur among the group of headache disorders referred to as the Trigeminal Autonomic Cephalgias; the word “trigeminal” refers to the nerve that allows sensation to be felt in the face and the word “autonomic” refers to the group of nerves that allow involuntary functions to occur such as blood vessel constriction / dilatation, pupil change, sweating etc.

The disorder is more common in men but can affect individuals of any age, occurring in approximately 1 in every 500 people of the population.

How do the symptoms of cluster headaches differ from other headaches?

The commonest type of headache in the population is migraine, a condition which is common, highly disabling and usually results in people taking to bed with a severe unilateral or bilateral headache that results in so called “migrainous” features of noise, light, smell and motion sensitivity, nausea and vomiting. People suffering migraine may often need to take to bed with attacks and these episodes may last hours or days.

If someone has a migrainous predisposition, then any type of headache they suffer may have such “migrainous” features. Cluster headache on the other hand is much rarer and typically causes patients to have attacks of severe pain that typically come on very quickly, affects just one side of the head or face, and these attacks may come at specific times of day, often waking a person from sleep early in the night.

Alcohol typically provokes an attack within minutes, as opposed to migraine where an attack more often follow the day after drinking. In cluster headache, the pain is so severe that it typically causes restlessness and severe agitation and people suffering an attack will find it difficult to stay still. They are often so agitated that they will rock or pace about the room or kneel on a bed or floor and push their head hard into that surface.

People suffering an attack will often pull their hair, press very hard into their head or eye or punch themselves very hard in a state of agitated desperation. Attacks usually result in prominent autonomic disturbance that causes the eye(s) to go bloodshot, droopy, puffy, twitch, or tear; the nose will often feel blocked or may run, the ear may feel full or there may be tinnitus, and the skin may go flushed and sweat. There may also be more typical “migrainous” features in the attack of cluster headache, for example stimulus sensitivity to noise or light or vomiting.

Up to a third of patients that we see with this condition will have a continuous background headache on the same side that is more bearable. Patients will typically live in fear of the next attack. Attacks may be infrequent and occur a few times a week but most patients will have between one and five attacks per day, some patients even more. A group of patients will have chronic cluster headache that continues month in and month out without stopping.

When we see patients going through a bout of cluster headache, they will more often than not have other symptoms related to severe fatigue and depression. In between attacks they may look relatively well and if they are seen by a healthcare practitioner who has not had much experience of this condition (e.g. a general practitioner, casualty officer or nurse), the overall severity and impact of their condition on their lives may not be taken seriously.

When should you seek advice about headaches?

In my opinion, any person suffering cluster headache should early on be seen by a specialist who both understands their condition and has experience in managing this disorder effectively.

It has unfortunately been all too common in the past for patients to go many years undiagnosed or incorrectly diagnosed and therefore without any effective treatment.

Practitioners who help manage headache disorders may include consultant neurologists, general practitioners with a specialist interest or some nurse practitioners who specialise in headache management.

If a patient is under one of these practitioners and is not gaining significant treatment benefit, then I am of the opinion that they should be referred to a consultant neurologist who specifically specialises in headache management.

What is thought to cause cluster headaches?

In the past, cluster headaches were thought to arise because of problems with blood vessels but increasingly it is recognised that cluster headaches are caused by abnormal nerve function within the brain.

The exact mechanism is still not fully understood but it is of interest that the attacks of cluster headache probably arise in an area of the brain adjacent to or involving the hypothalamus, the nerve control centre of our body clock mechanisms. This may explain why attacks appear to come at certain times of day or in certain seasons and even why some people find their cluster bouts switched on or off by travelling on long haul flights across many time zones.

The attacks clearly involve nerves within the pain and autonomic pathways in and outside of the brain. It is also recognised that chemicals that cause blood vessels to dilate such as calcitonin gene-related peptide (CGRP) are involved in the pain pathways.

Genetic mechanisms seem to play less of a role in developing these disorders than in migraine and we still do not what it is that makes someone likely to develop cluster headache.

Can cluster headaches be treated with over-the-counter painkillers?

The trouble with cluster headaches is that they are severe and typically come on very rapidly to full intensity pain. The attacks usually last between 20 minutes and four hours.

Taking over the counter painkillers will usually be totally ineffective. They take too long to be absorbed in the stomach to work and they are not good at targeting the pain here.

The two most effective types of treatments are prescribed drugs called triptans and the use of high flow oxygen, both of which will need to be started as quickly as possible in an attack. The triptans need to be injected but may sometimes work if nasally inhaled. This allows the drug to reach the bloodstream quickly and work on its target effectively.

These treatments can be quite costly and the guidelines produced in the UK by the National Institute of Clinical Excellence (NICE) suggest it is appropriate (i.e. medically appropriate, ethical and cost effective) to use up to two injectors of triptans per day, at a potential cost of approximately £1800 per month. This highlights the severity of the disorder and the need for effective treatments.

Why are cluster headaches difficult to treat?

I think the biggest obstacle remains the lack of full understanding about what causes cluster headache. While there is a lot of research into this disorder to help us to understand the mechanisms that lead to cluster headache, most treatments in the past have been found by chance or through trial and error. This is as a result of the lack of understanding around the exact areas that should be targeted, and which chemicals cause head pain.

We need patients to be diagnosed much earlier, they need to find their way quickly to effective treating centres and we need to find better ways of both treating acute attacks and preventing them from occurring in the first place.

We have a number of drug therapies that are likely to be effective in at least some patients but hardly any of these have been subjected to rigorous randomised studies. In addition many come at risk of potentially severe side effects, including cognitive and mood related effects.

For acute attacks we need something that works quickly to act on the nerve circuits and intervene to head off the attack and reduce pain quickly. This is where the opportunity to use handheld nerve stimulators holds such promise as a novel way of treating this condition.

What advances do you see in the pipeline for cluster headache therapies?

In the last few years we have seen new devices that can be surgically implanted to help prevent attacks or treat them quickly when they occur. However, these involve surgical operations and do not work in all patients and some devices have high complication rates. The sphenopalatine ganglion stimulator is the latest of these devices to be tested with positive results in clinical trials but the technology is still relatively new and this still involves an invasive procedure to insert the device in the face, attaching it to facial bones. Importantly however, this has been through good studies showing benefits. It is not cheap and is only just starting to be used in the UK. It requires highly specialist surgical and medical management to select appropriate patients and implant them effectively.

Our ideal treatments in the future should be safe, providing maximum clinical benefit with minimum risk of side effects or harm; they should be effective for as many people as possible and they need to be very cost effective in the current climate of rising costs of healthcare.

In the absence of an actual cure that will stop the condition for good, it will be ideal if we can avoid using drug therapies that come with high risks of adverse effects and if any physical treatments used can be minimally invasive.

Clinically rigorous studies have been utilising non-invasive nerve stimulators such as the gammaCore non-invasive nerve stimulator. This has recently been approved by the US Food and Drug Administration (FDA) in the United States for acute treatment of attacks.

gammaCore is a CE-marked medical device that allows patients to easily self-administer treatment for cluster headache, giving them back control over their condition. There is also evidence that it may help to prevent attacks and that it may be cost effective when compared to current existing treatments.

In addition to gammaCore, we have a number of studies that have started looking at the testing of an injectable therapy that may potentially reduce the number and severity of cluster headache attacks. These studies use human synthesised antibodies that potentially prevent the chemical  CGRP from acting within the brain to cause pain. There is significant hope that these treatments will be effective, resulting in injections that can be administered relatively infrequently (e.g. once a month) to help prevent attacks.

What research is taking place in this field?

Current research is aimed at both (1) elucidating the mechanisms whereby cluster headache occurs and affects sufferers, and (2) improving treatments. There is considerable work happening in both of these areas at the moment.

The importance of research to better improve our knowledge of what happens in cluster headache is that it will hopefully allow us to look at better ways of safely targeting the actual problem and this will undoubtedly improve our chance of finding better ways of preventing and treating attacks.

Ultimately this will also give us the best chance of one day finding an actual cure for a condition that ultimately ruins the lives of sufferers and their families.

Are there any particular hurdles that still need to be overcome?

There are many hurdles still to be overcome. The development of new treatments is a time consuming and very expensive process. Scientific progress in brain conditions is particularly difficult to achieve as the brain is such a complex organ and it is hard to know what happens in a human being having such attacks.

This is an evolving field, where ultimately more research and more funding are needed. In addition, the process to test new therapies is an expensive one and it is difficult for small companies with innovative ideas to be able to afford to do the sort of research that will see their ideas reach the patient.


What do you think the future holds for people that experience cluster headaches?

If we look back over the past 20 years, it is clear that we have improved education for all people involved in treating patients with headache disorders. Patients are more knowledgeable about their conditions and better able to help themselves. We have also seen increasing options for treatment over this time.

The most significant developments that I envisage will relate to safer, better targeted and less invasive treatments. I would like to see costs of treatment reduce with time but the development and testing of new treatments is extremely expensive.

In particular, I envisage the emergence of better targeted treatments that will help put the sufferer more in control of their own condition so that they are in a position to control the disorder rather than finding themselves completely at its mercy.

Where can readers find more information?

About Dr Nicholas Silver

Dr Nicholas Silver is a consultant neurologist at the Walton Centre NHS Trust, Liverpool. Dr Silver trained in neurology at The National Hospital for Neurology, the Institute of Neurology and Barts and the Royal London NHS Trust. He completed a PhD in interrogating new magnetic resonance techniques to better elucidate function and disease of the brain.

He established the first clinic for severe and refractory headache disorders in the North West United Kingdom and has clinical and research interests in cluster headache, chronic migraine, and hemicrania continua.

His main in interests are in the recognition of non-headache features of these disorders, their association with sleep disorders and their treatment with minimally invasive therapies.

Dr Silver continues to act as a Principal and Chief Investigator for a number of ongoing UK treatment trials into migraine and cluster headache at the Walton Centre. He is a scientific advisor to a number of companies that manufacture therapeutic drugs or devices for the treatment of cluster headache.

Dr Silver is actively involved in the British Association for the Study of Headache as a Council Member and he chairs a clinical governance committee for the Association of British Neurologists that looks at national guidelines and audit.

Dr Silver is a holder of the Les Charlton award from the Organisation for the Understanding of Cluster Headache (OUCH UK) for his services to cluster headache suffers.

April Cashin-Garbutt

Written by

April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.


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  1. David Nickerson David Nickerson United States says:

    Thank you! There is so much misinformation on Clusters (a recent BBC DITH epsiode for example). Refreshing to see an article that actually has current information instead of restating 20 year old recommendations.

  2. Cindy Reynolds Cindy Reynolds United States says:

    Thank you for the absolutely brilliant and thorough article.  The cluster headache patient community experienced a fairly nasty setback May 15th, 2017 due to a (television personality) implying, on air, how chiropractic care and healthy nutrition could be an undiscovered 'cure' the condition.  

    I'm a member of an online patient support group and feel thankful today to have my fellow patients for support, treatment options including citizen science, supplements and best practices for oxygen use.  Thank you so much for speaking to this amazing treatment, often sidestepped as an option, thinking the equipment is bulky, a hassle or inconvenient. If you give a cluster headache patient the option, we'll choose using an efficacious, zero side effects treatment to 'abort' these attacks.  Every single time, especially over concerning ourselves about bulky equipment.  Stopping that pain, with the least side effects is all we care about.  Denying oxygen for any reason, especially by insurance company's is inhumane.  

    What would be the most humane, would be to come up with a triage system, so the diagnosed cluster headache patient is able to access medical grade oxygen 24/7/365.  The nature of this extreme pain is cyclical, symptomatic and remitting.  As a patient, I'd love to see medicine recognize the sheer desperation & fear the patient experiences when a new cycle of headaches spontaneously appears. Having access to the single most effective abortive, without question, would reduce suicides.

  3. Joey Larkin Joey Larkin United States says:

    The pain I go there on a daily bases I've been dealing with this for over 7 years tryed so many different treatments many days I want to just give up.I stay in state of depression if any one can help me with more info or just so one to talk to that knows my suffering I suffer year around spring time seams the be the worse no relief..... Help.....

  4. Edward Fiorill Edward Fiorill United States says:

    Well that post about not having cluster headaches is not true. What I meant to say is that they have decreased in frequency from 3 times a day to only about 2 times a week, although these still last about 4 hours. Much better than before though.

  5. Shawn Dotson Shawn Dotson United States says:

    I first got these headaches in school in the 6th grade during class. I remember the intense pain and losing all focus (not visual) on what was going on. I grabbed my left eye like it was going to explode out of my head and my mouth agape. I couldn't talk or scream or make a sound but just sit at my desk in pain and shock not knowing what was happening. since then I have had them about 10-20 times a year till I was in my 20s and they seem to be coming less frequent although during 1 episode it lasted about 2 hours. a lot longer than normal as most lasted seconds to 5 min or so. I am in my late 40's now and I only have an attack maybe 2-3 times a year and most last only seconds (maybe 15-30). I have also gone up to 3 years without an attack at all. Not sure why but thankful. Now the interesting part is I have starting to suffer a new form of debilitating headaches that are almost as bad but not quite. I now have coughing headaches and they are random also and I fear every cough I let out that one will begin. They will usually happen 5-10 seconds after I cough and you can feel them build rapidly with a pressure in the back of your head to the back of your eyes. its a full on headache that lasts near 25-30 min that is nothing short of a severe migraine. they leave as rapidly as they come on after this time. Could these coughing headaches be linked in some way to cluster headaches? They almost feel as bad as cluster headaches but not localized behind one eye and one side of the head but rather the whole head. I have an appointment with an eye specialist in 2 days and have had coughing headaches for about 3 weeks now. Also I have eye/vision damage with a loss of about 15.20 percent of my vision in the left eye. The same eye affected by cluster headaches. Eye doctor took pictures and there is swelling at the back of my eye which look like blisters and ruptures of vessels with bleeding. I have never had any treatment for any of the headaches I have and was basically not believed as there were no signs or evidence to them ever happening. This will be my first ever visit to an eye specialist. I have had 1 cluster headache in the past 3 weeks that lasted about 5 seconds which is 5 seconds to long. I am hoping this is not the beginning of a new round of cluster headaches. A good possible contributing fact os I have very high blood pressure.  while taking an ACE inhibitor drug my blood pressure is between 240/150 to 190/140. Time to get my med dose raised I think and another dreaded visit to the doctors. I mainly try to avoid the doctors as they never seen to listen or have taken me serious all my life. I hope no one gets these headaches who have never had them. You don't want to experience that kind of pain. No one does. Probably not even dead people as I'm sure that would cause them to have a new condition called the screaming dead.

  6. Glyn Vee Twin Glyn Vee Twin United Kingdom says:

    An interesting article scientifically but of little help to sufferers who still have only an oxygen bottle which is not very compatible with work and other aspects of general life. However, at least the article is up to date, unlike so many that still say for example that painkillers don't work because cluster headaches are over by the time painkillers kick in (my CH attacks last 4 hours or more, easy enough time for a painkiller to begin work but they don't) so one glance at a sentence like that on a page tells me the page is outdated and useless. This page however is up to date. I am still awaiting though, to see info on any page that is fundamentally useful to myself or other sufferers. Until then, I am travelling about with a large bottle of oxygen and missing important meetings at work.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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