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Cluster Headache

Cluster Headache – Diagnosis – Associated symptoms – Triggers – Causes – Prognosis – Abortive, Transitional, and Preventive Treatment

Cluster Headache Diagnosis
Cluster headache is the most common syndrome out of all trigeminal autonomic cephalgias.

It is a relatively rear condition with incidence around 0.1%.
Cluster headache has unique headache quality and pattern, as well as striking associated symptoms. Yet, it is often misdiagnosed for years.An average cluster headache sufferer is correctly diagnosed on the seventh year, having seen 4 doctors and having 4 incorrect diagnoses prior to the correct one. The reason for the misfortune is a mystery.

One of the likely explanations for the delayed diagnosis is the fact that cluster headache sufferers have a unique type of personality. Unlike migraineurs, they don’t readily share their experiences and feelings. They don’t tend to elaborate on the symptoms but they do answer specific questions well. So, if the doctor does not ask the right questions, the correct diagnosis is never made. Besides, these guys don’t like going to doctors. They predictably miss follow up appointments even when they need their medications.

Pain quality in cluster headache is classically described as “the worst pain known to men”, or something like “people jump out of windows” while in pain. Cluster headache is often called a “suicide headache” as well.

I am not going to dispute those statements. Whether they are true or not, you will never hear these words from any cluster headache sufferer. All you are going to here is: “I have a headache, Doc”. They will confirm that the headache was “bad” but they would not elaborate much on the pain intensity. Sometimes, a witness may shed light on the headache intensity. Cluster headache attack makes people run around, or bang the head on a wall. They stick their heads in a freezer or in a scolding hot shower.
Unless the doctor is prepared, witnessing a cluster headache attack in the office does not help much. This guy may curse, get agitated, jump up and down during the interview but, surprisingly, may forget to tell about the headache. Presence of associated symptoms is very helpful in the diagnosis, if witnessed. No patient, however, is going to tell you that the eye was tearing, that the pupil was smaller, the eyelid was droopy, and that the nose was stuffed. They have to be asked about it.

Why do I use only “guy”, “he”, “him”? Official statistics states that female-to-male ratio in cluster headache is about 1:4, 1:2, or even recent 1:1. Where these numbers re coming from? Considering how many males with cluster headache I saw over years and I am yet to see the first female with this diagnosis, it does not look like ladies ever suffer this disease. I have never encountered a single woman with a definite cluster headache, ever. All those ladies diagnosed with cluster headache had anything else but cluster headache. They were simply misdiagnosed.

The first attack of cluster pain is always a concern. Multiple conditions may cause similar symptoms – Trigeminal neuralga, Tolosa-Hunt syndrome, carotid or vertebral dissection, brain aneurysm rapture, AVM (arterio-venous malformation), pituitary tumor, herpes zoster or temporal arteritis have to be ruled out. Once the headache pattern is established the diagnosis becomes very easy to make during an interview.
I am done with philosophical issues. Let’s proceed with more formal presentation of cluster headache.

Excruciating Pain in Cluster Headaches
Cluster headache produces one of the worst head pains, which is typically behind the eye, in the temple and it may sometimes travel to the neck. Cluster headache is almost exclusively unilateral (one sided). In 85% of cases it is always on the same side. Fifteen percent may switch sides from cluster to cluster and 5% switch sides within the same cluster.

Sufferers may feel like the eye is stabbed with a red-hot rod, or as if the skull is being drilled into. The intensity of pain may vary but this pain is never mild. Cluster headaches during the daytime are often less severe than those occurring at night. Attack frequency is typically between 1 and 3 times per day. Each attack may last from 15 minutes to 3 hours.

Cluster Headache Timing
Predictable timing of pain attacks is a trademark of cluster headache. They tend to happen at the same time every day. Especially striking is relation to the specific time at night. Nocturnal attacks typically strike 60 to 90 minutes after falling asleep, or during the first period of REM sleep phase. REM (Rapid Eye Movements) phase is when we have emotionally charged dreams. This phase normally recurs every 1.5 to 2 hours through the night.

Cluster headache earned the name due to headache recurrence pattern. It runs in clusters. Clusters last from 2 to 12 weeks. Pain free time between pain clusters averages from 6 months to 2 years. Clusters are often tied to a particular season. Some patients are unfortunate to develop a chronic cluster headache, when cluster headache attacks strike regularly for years with no mercy. Chronic cluster headache is harder to treat.

Cluster Headache Associated Symptoms
Lacrimation (tearing) and conjunctival injection (red eye) are the most common, followed by a stuffed or runny nose. Another typical associate is Horner’s syndrome – smaller pupil and droopy eye lid. The face looks red and puffy. These associated symptoms typically occur on the side of the pain, but they may be on both sides. Patients often self-diagnose with sinus pain. Light sensitivity, common in cluster headache, may lead to the diagnosis of migraine.

Staying still makes the pain worse, which is a good explanation for agitation, screaming, banging head against the wall, rolling on the floor or taking a hot shower while in pain. This behavior makes a striking difference from migraineurs, who tend to lie still in a dark and quiet place.

Some do look for a dark place and lay down but they don’t stay still and rather roll from side to side or bang the head on the wall.

Cluster Headache Triggers
Alcohol predictably triggers attacks during clusters but not during remissions (headache free period). Nitroglycerin, hot weather and possibly watching TV are common triggers as well.
Cluster Headache Causes and Associated Conditions
Occasionally cluster headache may develop as a consequence of head trauma. It is called secondary cluster headache.

Primary cluster headache is universally associated with smoking. Majority of patients start smoking prior to headache onset. A large percentage of cluster headache sufferers are heavy alcohol drinkers.

Pituitary disorders are often associated with headaches. Patients with pituitary disease and headaches are 100 times more likely (than general population) to develop a cluster-like pain.

Pituitary gland function is tightly controlled by the hypothalamus. Hypothalamus is a part of the brain involved in sleep-awake cycle, metabolism, endocrine system, body temperature control and lots of other functions.

Hypothalamus abnormal functioning is responsible for triggering cluster headache chain of events.

Cause and Mechanism of Cluster Headache (Pathophysiology)
Cluster headache is believed to be generated by abnormal function of posterior (rear part) of hypothalamus. This part of the brain has multiple functions, such as control of metabolism and sleep cycle, pain regulation, temperature regulation, body changes due to seasonal and day/night cycles (biological clock). This pretty much explains a clockwise regularity and seasonal variations of cluster headaches.

Cluster headache patients are known to have low testosterone and melatonin levels during clusters. This is the reason for melatonin effectiveness in some nocturnal cluster headache sufferers.

Hypothalamus has direct connections to the trigeminal nerve system, which carries pain sensation from the face and front of the head.

The precise mechanism of pain generation in cluster headache and other trigeminal autonomic cephalgias is yet to be discovered.

Prognosis in Cluster Headache
Episodic cluster headaches course is unpredictable. Some people have just a few brief bouts years apart, others have relatively regular clusters lasting for weeks and repeating a few months/years apart. It is normally a life-time disease but natural remissions lasting for many years or permanent resolution of the headache attacks do occur.

Chronic cluster headache has a generally less favorable prognosis but it does remit in some patients and sometimes permanently. I’ve seen all possible scenarios but it is impractical to predict what is going to happen in each particular person.

Technically, induction of a long lasting headache and medication fee remission with treatment cannot be promised or even hoped for. Nevertheless, I did have patients with relentless chronic cluster headaches for many years, who did get remissions after preventive treatment. It is hard to say if in those cases remissions occurred naturally or they were induced by the treatment.

Types of Cluster Headache Treatment
Having cluster headache is a challenging experience. Considering the treatment is adequate, cluster headaches are manageable in the vast majority of patients.

There are two types of approach: acute or abortive treatment and preventive treatment. Some neurologists also use transitional treatment.

Abortive Treatment for Cluster Headaches

Abortive Treatment for Cluster Headaches

Abortive, or as needed, treatment of cluster headache attacks encounters the following obstacles:

  • High frequency attacks (often more than one per day)
  • Severe pain requires fast acting, readily available, and easy to administer means of treatment
  • Short attacks make oral medications useless
  • Conventional pain medications have no use for cluster headache pain

For these reasons, fast and predictable relief within 20 minutes is expected from acute treatment.

Sumatriptan (Imitrex) in Cluster Headache

Sumatriptan injection is the most effective abortive treatment for cluster headache attacks. Three quarters of the patients have a complete relief of pain within 15 minutes.
Sumatriptan in the form of a nasal spray is less effective and the effect is delayed for up to 30 minutes.
Frequent use of Sumatriptan in cluster patients can increase the attack frequency after a few weeks of use.
It is recommended for short cluster periods and at the beginning of each cluster until preventive treatment kicks in.

Oxygen for Cluster Headache

Oxygen inhalation 7 to 10 L/min is a safe and effective abortive treatment.
Oxygen is less effective in chronic cluster headaches.
Inhalation of 100% oxygen should work within 20 minutes.
In some patients the pain comes back after the inhalation has stopped.

Other Abortive Treatments

Zolmitriptan (Zomig) is the only medication taken by mouth proven to be effective as abortive treatment. The efficacy is much lower than Sumatriptan injections.

Dihidroergotamine, as a nasal spray or an injection, is another option.

Transitional Treatment of Cluster Headache
Transitional therapy is a short term treatment until the preventive treatment kicks in. Preventive and transitional treatments are started at the same time.
I never use transitional treatment because the actual effect of preventive treatment becomes less uncertain.


A short treatment of Prednisone or Dexamethasone stops cluster headaches within 2 days in majority of patients with episodic cluster headache. I would not use it for longer than 2 weeks.
The problem is that steroids might work on almost any type of headache. Response to specific treatment is a part of diagnostic process in cluster headache management. Steroids are not helpful in this respect.

Occipital Nerve Blockade

Series of occipital nerve blockades control cluster headaches within 1 week in significant percentage of patients.
Moreover, there are reports that this procedure may even cause headache remission for days or may even completely abort the current cluster.

Naratriptan (Amerge)

Naratriptan is a long acting triptan. Taking Naratriptan by mouth twice a day for a few days is a reasonable transitional treatment or even short term preventive treatment for patients with known short cluster periods.
Long term use of triptans in not recommended in cluster headache due to potential rebound effect resulting in increased frequency of attacks.
Another issue is lack of medical coverage for brand and more expensive triptans.


Dihydroergotamine, administered intravenously for a couple of days, stops cluster cycle for days or even months in majority of patients with episodic and in more than half of chronic cluster headache patients.
It gives plenty of time to initiate preventive treatment. Due to potential side effects this treatment has to be given in a hospital setting.

Cluster Headache Prophylaxis - Preventive Treatment
Preventive treatment is meant for a long term control of cluster type of headaches. Treatment duration will depend on the cluster life span in an individual patient. Chronic cluster headache may require preventive treatment for indefinite period of time.

One of the questions in preventive treatment is the length of treatment. Since there is no point for prophylaxis outside the cluster, it is nice to know when the cluster is over. Considering patients are typically diagnosed with cluster headache after years of suffering, an average length of a cluster for each particular case is usually well known.

For newly diagnosed cases this might be a challenge. Since majority of patients with cluster headache drink alcohol relatively frequently, it might help to identify the the end of the cluster. Outside cluster period alcohol fails to trigger headache attacks.

Besides headache attack prevention, prophylactic treatment might induce a long lasting remission in occasional patients.

Verapamil (Calan)

Verapamil is the best drug to start with. It is well tolerated and is pretty effective. Immediate release formulations are taken about three times a day and sustained release may be taken from one to two times per day.

The effect is delayed by 1 to 2 weeks. A high dose (up to 960 mg per day, if tolerated) has to be tried before calling the treatment a failure. The heart has to be monitored with EKG after each doze adjustment.

Even though I didn’t see it in the literature, Verapamil may induce remission. One of my patients with chronic cluster headache for 15 years had a few years of remission with subsequent conversion to episodic form after Verapamil treatment for a few months.


Historically, Lithium is a mainstay of cluster headache prevention, but its side effect profile makes it less desirable. It appears to be more effective for chronic cluster headache.

Narrow therapeutic window (little difference between the toxic dose and the effective dose) limits its use to patients who do not respond to other treatment options.

Response of headache to lithium appears to be developing slower than to Verapamil.Lithium level, thyroid and kidney functions have to be regularly assessed during therapy.
The most common side effects are tremor, diarrhea and large urine volume.


Melatonin level is decreased in cluster headache patients, more so during the cluster period.

It is available as a supplement only. It is more effective for nocturnal headaches in episodic cluster headache than in chronic and daytime headaches.

Melatonin may control cluster type of headache within 24 hours in some patients. Based on my experience, Melatonin 10 mg nightly does work in some patients pretty well.

Due to lack of standards in supplement industry it is hard to rely on this drug as a single agent. A combination of lower dose Verapamil with Melatonin is a decent option.


Topiramate (Topamax) is a decent option in low to moderate doses. High dose (above 100 mg per day) may increase cluster headache attack frequency.

Topamax finds its best use as an additional to other drugs agent. I use it as initial treatment if Verapamil is contraindicated or poorly tolerated.

Unlike Verapamil, Topiramate does not control headaches completely but it does make them less severe or less frequent.

Hallucinogens (LSD 25 and Psilocybin)

These agents are claimed to be effective for cluster headache prevention and even for remission induction in sub-hallucinogenic doses. Whether it is true or not, it is hard to imagine that any study is going to be ever approved. These agents may worth some attention as potential clue for the future drug development.

On the other hand, controlled and illicit drugs are always hyped and look attractive. Those claims might be unsubstantiated.