Ed Tompkins will never forget the first time he had a cluster headache. A pain more intense than any he had ever experienced—"It was like a bomb went off in my brain"—woke him up early one morning when he was 13. He paced in agony for the next couple of hours before vomiting and finally feeling the headache disappear.

That harrowing event turned out to be the start of a bout of headaches that would alarm him and his parents and befuddle his doctor. An MRI ruled out a tumor or other potential structural causes of the pain, but the headaches didn't fit the typical patterns of migraine or sinus headaches.

For years Tompkins endured these torturous attacks with nothing more than acetaminophen or aspirin. He came to dread the havoc it would wreak on his life. It wasn't until he was in college that he was correctly diagnosed with cluster headache.

Tompkins, now 59, has finally found treatments that relieve his pain, but it's never easy dealing with the headaches. Accessing the treatments quickly is tricky. And the severity never wanes. "If untreated, it stays at an unbearable intensity the whole time," he says.

A cluster headache starts abruptly, with pain peaking in intensity within a few minutes, says Deborah I. Friedman, MD, FAAN, director of the Headache and Facial Pain Program at the University of Texas (UT) Southwestern Medical Center in Dallas. "The pain is centered around the eye or forehead and is excruciating—like being stabbed in the eye with a knife, hot poker, or dagger," she says.

Pain often starts within the upper trigeminal region of the face, around the eye, and may spread into the teeth, jaw, neck, or back of the head. And people usually experience at least one symptom related to the autonomic nervous system, which operates mainly unconsciously and controls bodily functions like heart rate, explains Dr. Friedman, also a professor of neurology and neurotherapeutics at UT. "These symptoms—such as bloodshot or swelling eye, droopy eyelid, a small pupil, stuffy or runny nose, facial flushing, or a sense of fullness in the ear—occur on the same side as the pain," she says. The headaches often come at night and may disrupt sleep.

During attacks, people become agitated and may pace, rock in a chair, or hurt themselves to try to distract from the overwhelming pain of the headache.

"I always want to move because when I lie down, it hurts more," confirms Tompkins. "I hit my head with my hands to try to push the pain to a different part of the head."

"It is so severe that many people have thoughts of suicide during one," Dr. Friedman says. A study published in the journal Cephalalgia in April 2018 bears this out. In interviews with headache specialists, researchers found that people with headache disorders accounted for 1 percent of suicides worldwide—and 70 to 80 percent of them had cluster headache or migraine. People with cluster headache were more at risk than those with migraine, according to the report. In addition, suicide attempts were 10 times more common than actual suicides.

As the name suggests, these headaches are clustered within spans of time—anywhere from three weeks to several months—separated by remission periods. "In episodic cluster, the headache periods may occur once or twice a year, but the range of periods is variable," says David B. Kudrow, MD, director of the Headache Clinic Harbor-UCLA Medical Center. "Some patients may have cluster periods every two to three years, and we've seen cases in which cluster periods occur every nine years." They commonly last four to eight weeks. In chronic cluster headache, cluster periods last at least a year with remission periods lasting less than three months, says Dr. Kudrow.

Unknown Mechanism

Although scientists aren't certain what causes cluster headache, they think it originates in the hypothalamus, Dr. Friedman says. This brain region regulates thirst, hunger, circadian rhythms (like the sleep-wake cycle), emotions, body temperature, and other hormone-related processes.

"The parasympathetic nervous system accounts for the tearing, stuffy or runny nose, and eyelid swelling," says Dr. Friedman. "These [parasympathetic] fibers run through a structure called the sphenopalatine ganglion (SPG), located behind the nose, which is a relay station for the nerves."

Smoking (or a history of smoking) and sleep disorders are among the primary risk factors for cluster headache, and men are at higher risk than women. "Genetic risks probably exist, as one in 20 patients has a relative with cluster headaches," says Morris Levin, MD, FAAN, professor of neurology at the University of California at San Francisco and director of the UCSF Headache Center.

Potential triggers of cluster attacks include alcohol, high altitude, and, sometimes, vigorous exercise, says Dr. Kudrow.

The pattern of cluster headache should make the condition easy for doctors to identify, but that is rarely the case, says Matthew Robbins, MD, FAAN, director of the neurology residency program at Weill Cornell Medicine and New York Presbyterian Hospital in New York City. "Unfortunately, most patients take years to get a proper diagnosis," he says. "This delay is often because of pain centered in the eye or because of symptoms blamed on sinus, eye, or dental problems."

Some symptoms are also associated with migraine. Yet the pain of cluster headache is more severe than that of migraine. "Cluster headache differs from migraine in several ways," Dr. Robbins says. "In most people, the attacks are clustered in bouts and have a rhythm, often happening at the same time of day or night or at similar times each year. The attacks are typically shorter than those of migraine." During a cluster attack, people feel they cannot stay still or rest, while those with migraine find movement makes the pain worse.

Finding Relief

Although cluster headache can be one of the most vexing types to treat, a widening array of therapies are available. "Because the pain peaks so quickly and is so severe, acute treatment—used to shorten an attack—needs to work rapidly," says Dr. Friedman.

Options include high-flow 100 percent oxygen, which usually works in about 10 minutes. (Oxygen decreases cerebral blood flow, which is known to increase during cluster headaches.) Patients often keep a large tank of oxygen at home and carry smaller ones with them in case headaches strike while they're out.

Nasal and injectable versions of triptans, medications approved for migraine, also stop cluster headaches quickly and effectively for many patients, possibly by reducing levels of calcitonin gene-related peptide, a molecule elevated in people with cluster headache, or by preventing pain signals from being sent to the brain.

Ergotamine tartrate and dihydroergotamine, pain relievers thought to cause blood vessels to constrict, may be prescribed, but these ergot derivatives can cause nausea or vomiting. "Applying lidocaine [a local numbing anesthetic] into the back of the nostril on the side of the pain, either with cotton swabs or a nasal spray, is occasionally helpful, presumably because the lidocaine is absorbed into the SPG," says Dr. Friedman.

The newest treatment, a device called gammaCore, stimulates the vagus nerve, which runs from the head to different parts of the body and regulates many functions, including pain. Recently approved by the US Food and Drug Administration (FDA), gammaCore appears to work by blocking pain signals. "The device sends a mild electric current to the vagus nerve in the neck and can stop a cluster headache in as little as 15 minutes," says Dr. Friedman. "Applying the stimulation daily can reduce the frequency of attacks overall."

Preventive treatments are started as soon as the initial attack begins. They include the calcium channel blocker verapamil, given in progressively higher doses. "As doses increase, side effects include constipation and possible slowing of heart rate, so monitoring with electrocardiography (ECG) is necessary," says Dr. Kudrow. Lithium (a psychiatric medication that helps to regulate the hypothalamus), the corticosteroid prednisone, and, in some cases, the anti-seizure medication topiramate also may be used.

Because it takes a while for preventive medications to start working, treatments may be needed to curb pain until they do, says Dr. Robbins. Such "bridge" treatments include a steroid injection in the back of the head or a course of steroid pills, which can reduce the inflammation associated with these headaches.

Ed Tompkins has tried many of the available treatments, with varying success. Ergot derivatives worked only about half the time. When the migraine medicine sumatriptan was introduced, it was a godsend. "Within 10 minutes my headache was completely gone," he says. "The problem was that I was having a headache every day for weeks, and the FDA recommends just two doses a week and that's all insurance would allow. I had to decide which days I was going to suffer."

Now, Tompkins relies on verapamil for prevention and sumatriptan or high-flow oxygen at the start of an attack. This combination has made his cluster headache easier to live with. "Based on case studies I've read," he says, "I think I'm lucky that I am able to control my bouts of headaches somewhat."

Smart Ways to Manage Cluster Headache

Find a specialist. The most important thing you can do to address cluster headache is to see a neurologist who specializes in the condition, one who has experience with cluster headache and is informed about emerging treatments.

Be prepared to try different therapies. In most cases, a combination of acute and preventive treatments is required to manage these headaches. You may need to go through a process of trial and error to find a regimen that helps. Cost and side effects of headache therapies also have to be considered.

Get support from other patients. "Cluster headache is so rare that most people have never met another person who has the disorder," says Deborah I. Friedman, MD, FAAN, director of the Headache and Facial Pain Program at the University of Texas Southwestern Medical Center in Dallas. But patients can find information—and community—in online support groups. 

3 Promising Therapies for Cluster Headache

1. Galcanezumab. Blood levels of calcitonin gene-related peptide (CGRP), a molecule that plays a role in migraine and other headaches, are elevated in people with cluster headache, as they are in many people who experience migraine, says Deborah I. Friedman, MD, FAAN, director of the Headache and Facial Pain Program at the University of Texas Southwestern Medical Center in Dallas. New drugs approved for migraines which block the activity of CGRP may be helpful for cluster headache patients. A clinical trial of galcanezumab, one such anti-CGRP monoclonal antibody, found it to be effective for the preventive treatment of episodic cluster. Galcanezumab was approved by the FDA for this use in June 2019.
2. Another peptide. Researchers are also focusing on pituitary adenylate cyclase-activating polypeptide-38, a peptide released from the blood vessels supplying the lining around the brain, similar to CGRP. It is present in the sphenopalatine ganglion (SPG), a relay station for nerves that's located behind the nose and believed to be involved in cluster headaches. Results of an exploratory study were published in The Journal of Headache and Pain in 2016.
3. Pulsante. This device stimulates the SPG with electrical pulses to interfere with pain messages before they reach the brain. In a large open-label study in Europe, SPG stimulation was effective in about 68 percent of people with cluster disorder, reported The Journal of Headache and Pain in January 2018. "This is the first treatment ever found to be effective for preventing the chronic form of the condition," Dr. Friedman says. The Pulsante device is inserted near the SPG through an incision in the gumline and anchored into the upper jawbone with small screws. A separate transmitter about the size of a cellphone is held up to the cheek to deliver the stimulation. The system is under review by the US Food and Drug Administration.
   
   Updated June 21, 2019, to add that galcanezumab has been approved by the FDA.

Advocacy and Support Groups for Cluster Headache

• Alliance for Headache Disorders Advocacy
• American Migraine Foundation; 856-423-0043
• BrainandLife.org/ClusterHeadache
• Cluster Headache Support Group; 785-330-5108
• ClusterBusters
• Coalition for Headache and Migraine Patients
• National Organization for Rare Disorders (NORD); 800-999-6673; 203-744-0100
• Worldwide Cluster Headache Support Group

Web Extra

See more information about drug trials and patient registries for cluster headache.