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All cluster headache patients require treatment. Other primary headache syndromes can sometimes be managed non-medicinally but in regard to cluster headache, medication, sometimes even polypharmacy, is indicated. Cluster headache treatment can be divided into three classes. Acute therapy is treatment given at the time of an attack to treat that individual attack alone. Transitional preventive therapy can be considered an intermittent or short-term preventive treatment. An agent is started at the same time as the patient’s true maintenance preventive. The transitional therapy will provide the cluster patient attack relief while the maintenance preventive is being built up to a therapeutic dosage. Maintenance preventive therapy consists of daily medication, which is supposed to reduce the frequency of headache attacks, lower attack intensity, and lessen attack duration. The main goal of cluster headache preventive therapy should be to make a patient cluster-free on preventives even though they are still in a cluster cycle. As most cluster headache patients have episodic cluster headache, medications are only utilized while a patient is in cycle and stopped during remission periods. [1]

° Sumatriptan

Subcutaneous sumatriptan is the most effective medication for the symptomatic relief of cluster headache. In a placebo-controlled study, 6 mg of injectable sumatriptan was significantly more effective than placebo, with 74% of patients having complete relief by 15 minutes compared with 26% of placebo-treated patients.61 In long-term, open- label studies, sumatriptan is effective in 76% to 100% of all attacks within 15 minutes even after repetitive daily use for several months.62 Sumatriptan is contraindicated in patients with uncontrolled hypertension, and past history of myocardial infarction or stroke. As almost all cluster patients have a strong history of cigarette smoking, the physician must closely monitor cardiovascular risk factors in these patients.

Sumatriptan nasal spray (20 mg) has been shown to be more effective than placebo in the acute treatment of cluster attacks. In over 80 patients tested, intranasal sumatriptan reduced cluster headache pain from very severe, severe, or moderate to mild or no pain at 30 minutes in 58% of sumatriptan users versus 30% of patients given placebo on the first attack treated, while the rates were 50% (sumatriptan) versus 33% (placebo) after the second treated attack.63 Sumatriptan nasal spray appears to be efficacious for cluster headache but less effective than subcutaneous injection. Sumatriptan nasal spray should be considered as a cluster headache abortive in patients who cannot tolerate injections or when situationally (e.g., an office settingjinjections would be considered socially unacceptable.

In many instances cluster headache patients may need to use sumatriptan more than one time in a day for days to weeks at a time. There is still controversy over whether cluster headache patients can develop medication overuse headache. Even though daily sumatriptan may be benefiting a cluster headache patient the goal should be to have them cluster-free on preventive medication and not using abortives to achieve cluster- free status.

° Inhaled Oxygen

Oxygen inhalation has been a well-known therapy for cluster headache dating back to the 1950s. What has changed is dosing, where now high-flow oxygen up to 15 liters per minute (LPM) is the norm, whereas for many years the dosing schedule was only 7-10 LPM. Typical dosing is 100% oxygen given via a non-rebreather face-mask at 12-15 liters per minute for 20 minutes.6465 In some patients, oxygen is completely effective at aborting an attack if taken when the pain is at maximal intensity, while in others, the attack is only delayed rather than completely alleviated. It is not uncommon for a cluster patient to be headache-free while on oxygen but immediately re-develop headache when the oxygen is removed. Oxygen is overall a very attractive therapy as it is completely safe and can be used multiple times during the day.

See Table 9.2 for acute treatment options. In patients with known coronary artery disease or past stroke or myocardial infarction #s 2, 6-13 can be alternative treatment options. [2]


Acute Treatment Options for Cluster Headache

1. Sumatriptan injection or nasal spray

2. 100% oxygen: via non-rebreather face mask at 12-15 LPM

3. Zolmitriptan: 10 mg > 5 mg PO or nasal spray

4. DHE injection

5. Ergotamine: PO, suppository

6. Intranasal lidocaine (4%)

7. Olanzapine: 2,5-10 mg PO

8. GON block: if in office or ED

9. Chlorpromazine supp 25-100 mg

10. Indomethacin supp 50 mg repeat q 30 minutes

11. Rare opiates or butorphanol

12. Subcutaneous octreotide 100 pg

13. External vagal nerve stimulator

° Corticosteroids

A short course of corticosteroids is the most recognized transitional therapy for cluster headache. Typically within 24 to 48 hours of administration patients become head- ache-free and by the time the steroid taper has ended the patient’s maintenance preventive agent has hopefully started to become effective. Prednisone or dexamethasone are the most typically used corticosteroids in cluster headache. A typical taper would be 80 mg of prednisone for the first 2 days followed by 60 mg for 2 days, 40 mg for 2 days, 20 mg for 2 days, 10 mg for 2 days, then stopping the agent.

° Dihydroergotamine

Intravenous DHE is an attractive transitional treatment but is more labor-intensive because patients either need to be admitted or brought to an outpatient infusion center for therapy. Typically within 1 or 2 days of repetitive DHE treatment cluster attacks stop and will not return for days to months. This allows time for a maintenance preventive agent to be started, and when the effects of the DHE wear off the true maintenance preventive’s effects have already kicked in.

° Occipital Nerve Blockade

Greater occipital nerve blockade using a combination of an anesthetic (e.g., lidocaine) and steroid (e.g., triamcinolone) can prevent cluster headaches attacks. They may be used to try to abort an episodic cluster headache cycle or be used as a transitional or even maintenance preventive in some. Either typical GON-based or suboccipital- located injections appear helpful.66-68

• Preventive Therapy

Preventive agents are absolutely necessary in cluster headache patients unless the cluster periods last for less than 2 weeks. Preventive medications are only used while the patient is in cycle and they are tapered off once a cluster period has ended. If a patient decides to remain on a preventive agent even after they have gone out of cycle this typically does not appear to prevent a subsequent cluster period from starting. The maintenance preventive should be started at the time a transitional agent is given. Most physicians treating cluster headache will increase the dosages of the preventive agents very quickly to get a desired response. Very large dosages, much higher than that suggested in the PDR, are sometimes necessary when treating cluster headache. A well-recognized trait of cluster patients is that they can tolerate medications much better than non-cluster patients. Most of the recognized cluster preventives can be used in both episodic and chronic cluster headache (Table 9.3).


Cluster Headache Preventives "Big 7"

• Verapamil short-acting preferred—may need to push doses to high levels (800 mg plus); EKG with every dose change above 480 mg

• Lithium carbonate (300 mg): 300 mg TID or higher depending on serum levels

• Valproic acid (250 mg): 1000-3000 mg (ER formulation)

• Daily corticosteroids—if short cluster periods (1-3 weeks)

• Topiramate-average dose is 75-100 mg

• Melatonin—9 mg QHS

• Methylergonovine—must come off every' 6 months for testing (0.2-0.4 mg TID)—only have DHE as abortive

*May work better in female cluster.

New Cluster Headache Therapies


• Demand Valve Oxygen A demand valve delivers oxygen to the user as soon as they try to inhale from an attachedmask; thus dosage is controlled by respiration rate and tidal volume. If the user inhalesmore deeply, more oxygen will flow in response to the increased demand, hence thename. Unlike a continuous-flow oxygen regulator (CFO), a demand valve is capable ofdelivering 100% oxygen from 0 to 160 LPM. One benefit of a demand valve is that itcan also support hyperventilation. CFO regulators are typically limited to 15 LPM, thusincapable of supporting hyperventilation. Hyperventilation leads to a state of hyper-oxia and hypocapnia. Based on its mechanics, a demand valve assures the delivery of100% oxygen without dilution by room air, which plagues delivery via nasal cannula andnon-rebreather face masks. Two studies have now suggested that demand valve oxygentherapy may be superior to CFO via non-rebreather face mask for time to pain relief,complete pain freedom rates, and a possible preventive effect for cluster headache. Theneed for hyperventilation with a demand valve versus non-hyperventilatory breathingneeds further study.6970 • External vagal nerve stimulator: now FDA-approved for the acute treatment of episodic butnot chronic cluster headache. Provides a non-medicinal treatment option.71 • Sphenopalatine ganglion stimulation is an implantable wireless stimulator which hasshown both a positive effect to acutely abort a cluster headache but also appears to have amaintenance preventive effect when used as a prn abortive. At time of this writing it is notyet FDA-approved72


Clomiphene Citrate Small studies have shown that clomiphene citrate, a hypothalamic estrogen modulator, canbe a unique CH preventive agent in treatment refractory CH cases.73-75 Clomiphene citrateappears to act as an estrogen agonist via ER alpha and as an estrogen antagonist via ERbeta on human hypothalamic receptors. Clomiphene citrate potentially acts as a CH preventive by modulating orexin, as estrogen and ER alpha receptors co-localize with orexinin the hypothalamus. Dosing: 50 mg QD for 2 weeks, then if no improvement 75 mg QD x 2 weeks, then if noimprovement 100 mg QD x 2 weeks—do not go higher on dosing if patients fails 100 mg.

Only suggested in males and post-menopausal females.

Risks: potential clotting issues (especially in females) and a heightened risk of testicular cancer and prostate hypertrophy—so if treatment is long term, yearly testicular and pros- tate/PSA exams will be needed.

• Monoclonal CGRP antibodies: the same agents that are now FDA-approved for migraine prevention may end up showing efficacy in episodic but not chronic cluster headache based on phase 3 trials.

  • [1] Acute Therapy The goal of abortive therapy for cluster headache is fast, effective, and consistent relief. There is no role for over-the-counter agents or butalbital-containing compounds and little if any need for opiates. Abortives need to show effect usually within 20 minutes as the attacks are short in duration.
  • [2] Transitional Therapy Transitional cluster therapy is a short-term preventive treatment that bridges the timebetween cluster diagnosis and the time when the true traditional maintenance preventive agent becomes efficacious. Transitional preventives are started at the same time themaintenance preventive is begun. The transitional preventive should provide the clusterpatient with almost immediate pain relief and allow the patient to be headache-free ornear headache-free while the maintenance preventive medication dose is being taperedup to an effective level. When the transitional agent is tapered off the maintenance preventive will have kicked in; thus, the patient will have no gap in headache preventivecoverage.
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