Treatment of Cluster Headache

The International Classification of Headache Disorders 3-Beta lists Cluster Headache with the Trigeminal Autonomic Cephalgias, as an entity separate from migraine, although they have many similar features.  Many persons with cluster headache have family members with migraine.  Cluster headache predominates in men, four times as frequent as in women.  The age range is usually mid- twenties to about sixty.  These are very severe, quick onset, one sided headaches which consist of pain around the eye, temple, or cheek.  There may be characteristic accompanying symptoms on side of the face, such as: drooping of the upper eyelid, smallness of one pupil, sweating above the eye, redness of the eye, tearing of one eye, nasal congestion, or drainage of clear fluid.  The headaches come in time periods called clusters which usually last 6-8 weeks and consist of 1-8 headaches a day, lasting 20-40 minutes.  The patient usually gets up and paces around the room.  Nausea, vomiting, and sensitivity to light and sound may occur, but are not as prominent as that which occurs with migraine.  The onset to peak of the headache is very quick—often in minutes.  The headaches may track the clock, coming at the same time every day and they may characteristically occur one to two hours after going to sleep.  During the cluster period drinking alcohol may aggravate the headache, but not at other times.  The patients often have a driven, type A workaholic nature.

Treatment options

 Hydrocortisone (prednisone, medrol dosepack) given orally for 7-10 days for cluster, will sometimes stop the attack.

Preventive treatment

Depakote (Divalproex sodium) Comes as a delayed release oral capsule 125 mg, oral tablet 125, 250, 500 mg, and oral tablet extended release 250, 500 mg. The typical dose for migraine is 750-1500 mg given in divided doses.  The initial dose for cluster headache is 250 mg bid and a typical dose of 600 to 2000 mg may be used for cluster headache.  Common side effects—alopecia, weight gain, nausea, and tremor.  Serious side effect—pancreatitis, liver failure, and thrombocytopenia.  Blood levels can be monitored.  Depakote is a Class X risk for severe fetal teratogenic effect and shouldn’t be given to potentially fertile women.

Lithobid (lithium carbonate) Comes as an oral capsule 150 mg, 300 mg, 600 mg, oral tablet 300 mg, and oral tablet extended release 300 mg, 450 mg. The typical dose for cluster headache is 600-900 mg/day in divided doses.  Common side effects--drowsiness, tremor, urinary frequency, thirst.  Serious side effect—nephrotoxicity and hypothyroidism.  Monitor blood level periodically.

Verapamil ER This is the treatment of choice for prevention of cluster headache.  Comes as an oral capsule extended release 100, 120, 180, 200, 240, 300, and 360, oral tablet 40, 80, and 120 mg, oral tablet extended release 120, 180, and 240 mg, and oral tablet extended release 24 hour 180 and 240 mg.  The initial dose is 80-160 mg and the typical dose for migraine and cluster headache is 160-480 mg although occasional higher doses up to 960-1200 mg have been used for cluster headache.  Common side effects--constipation, congestive heart failure, pedal edema, AV block, dyspnea, and inhibition of sperm motility (possibly resulting in infertility).  Serious side effects—hypotension and dysrhythmias.  It is advised to check EKG at baseline, at dose escalation, and every 6 months for long-term maintenance.  The EKG abnormalities are not dose-dependent and can occur in patients on doses as low as 240 mg/day.  Some clinicians favor using the short rather than long acting preparation for ease with dose titration.  “Neurological doses” (usually higher than 240 mg/d) have more potential serious heart block side effects than “cardiovascular doses” (80-240 mg/day).

Acute treatment

Nasal Oxygen is effective for cluster patients, and some migraine patients with clusters of short, quick headache.  Oxygen is delivered from a canister through plastic tubing through a non-rebreather face mask at a flow rate of 6-15 liters/min.  This is safe, rapid, and usually effective treatment for cluster headache.  Oxygen treatment may be effective in 10 minues.  Oxygen is not a drug, so there are no side effects.  Insurance companies may or may not pay for the tank,the oxygen, and the equipment.

General triptan rules—don’t use with a personal or strong family history of coronary artery disease.  Don’t use with uncontrolled hypertension.  Limit the dose in children, the elderly (defined here as over 65 years old.), and patients with basilar artery or complicated migraine (aura symptoms over 40 minutes.)  Don’t mix the triptans or take with ergotamine within 24 hours.

Common triptan side effects--chest tightness or pressure, near fainting, neck/back pain which may be burning, warm or hot, dizziness, or drowsiness.

Imitrex (sumatriptan) most effective when given via a gun type injector.  The medicine comes in a vial with a needle and is loaded into the injector like a bullet.  The medicine is then injected subcutaneously by pushing a trigger.  This is a very slick, high tech system.  The dose is 1 injection (6, 4, 3 mg) at the onset of the cluster.  Injjectable sumatriptan onset of treatment is 10 minutes and it gives the highest dose in the brain of any triptan delivery system.  Sumavel DosePro is pressure jet application of 6 mg of sumatriptan needle free through the skin.  An Imitrex nasal spray is also available as 5,20 mg squirt per nostril per cluster.  Although medication overuse headache with triptans (taking sumatriptan more than 10 days per month) can develop, it is rare with cluster headache patients and generally patients should treat their severe, quick, repetitive, “suicide” headaches with a triptan whenever the headaches come—which may be 1-8/day.  There are reports of medication overuse headache with cluster treatment.  A realproblem is getting insurance to pay for it as they see sumatriptan as only indicated for acute therapy of migraine and won’t give enough medication for cluster.  The physician should try an insurance override in this situation.

Zomig (Zolmatriptan) should decrease the dose by 50% if taken with Tagamet (Cimetidine).  Comes as a 2.5 mg or 5 mg nasal spray with onset of activity at 10 minutes.  Dose at onset 2.5 or 5 mg, may repeat in 2 hours.  

Articles regarding rare development of medication overuse headache during treatment of Cluster Headache follow:

Neurology. 2006 Jul 11;67(1):109-13.

Medication-overuse headache in patients with cluster headache.

Paemeleire KBahra AEvers SMatharu MSGoadsby PJ.

Headache Group, Institute of Neurology, Queen Square, London, UK.

OBJECTIVE: Medication-overuse headache (MOH) in cluster headache (CH) patients is incompletely described, perhaps because of the relatively low prevalence of CH. METHODS: The authors describe a retrospective series of 17 patients (13 men, 4 women) with CH who developed MOH in association with overuse of a wide range of monotherapies or varying combinations of simple analgesics (n = 9), caffeine (n = 1), opioids (n = 10), ergotamine (n = 3), and triptans (n = 14). The series includes both episodic (n = 7) and chronic (n = 10) CH patients. RESULTS: A specific triptan-overuse headache diagnosis was made in 3 patients, an opioid-overuse headache diagnosis was made in 1 patient, and an ergotamine-overuse headache diagnosis was made in 1 patient. In approximately half of the patients (n = 8), the MOH phenotype was a bilateral, dull, and featureless daily headache. In the other 9 patients, the MOH was characterized by at least one associated feature, most commonly nausea (n = 6), exacerbation with head movement (n = 5), or throbbing character of the pain (n = 5). The common denominator in 15 patients was a personal or family history, or both, of migraine. The 2 other patients gave a family history of unspecified headaches. Medication withdrawal was attempted and successful in 13 patients. CONCLUSIONS: Medication-overuse headache is a previously underrecognized and treatable problem associated with cluster headache (CH). CH patients should be carefully monitored, especially those with a personal or family history of migraine.

PMID: 16832088

Funct Neurol. 2000 Jul-Sep;15(3):167-70

Sumatriptan overuse in episodic cluster headache: lack of adverse events, rebound syndromes, drug dependence and tachyphylaxis.

Centonze V, Bassi A, Causarano V, Dalfino L, Cassiano MA, Centonze A, Fabbri L, Albano O.
Dept of Internal Medicine and Public Medicine, University of Bari, Italy.

This observational study was designed to examine the pattern of sumatriptan use in patients with cluster headache using more than the recommended daily dose of subcutaneously injected (s.c.) sumatriptan. Thirteen patients suffering from episodic cluster headache were asked to record the characteristics of their attacks and drug intake for 1 year. All reported a high daily frequency of attacks (more than 3 per day) and the related overuse of s.c. sumatriptan. The results show that the overall incidence of adverse events among patients receiving sumatriptan injections for the treatment of cluster headache is low. The extended administration of this drug in episodic cluster headache did not result in tolerance problems or tachyphylaxis. Only 4 patients experienced minor adverse events and recovered more slowly than the others. They suffered from migraine without aura and cluster headache, and showed a family history of migraine. Even though they must be viewed with caution, due to the observational nature of the study and the low number of patients included, these results suggest that the profile of sumatriptan may differ in cluster headache compared with migraine.

PMID: 11062845