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CloseTreatment Options for Cluster Headaches
Drug Therapy
There are two levels involved in the management of cluster headache with medication:
- Abortive treatment - relief of the acute attack
- Prophylactic (preventive or maintenance) treatment - prevention of future attacks
Abortive treatments are used to interrupt an existing headache. Prophylactic treatments can be used as transitional treatments, when strong abortive medications are given until longer acting drugs take effect, or as long term prophylactic treatments which are given for the duration of the cluster period. For most patients, medications to meet both of these goals are recommended.
Abortive Treatments
- Oxygen therapy
- Triptans
- Corticosteroids
- Ergot alkaloids
- Intranasal lidocaine
- Analgesics
Oxygen Therapy
Oxygen is an excellent abortive therapy for cluster headache and, surprisingly, many cluster patients have never been treated with oxygen therapy. Typical dosing is 100% oxygen given via a facemask at 7 to 10 liters per minute for 20 minutes while the patient is in an upright, sitting position. This therapy has been shown to be effective for pain relief in 60-80% of cluster headache patients. Most patients achieve pain relief within 10-20 minutes after starting oxygen. If there is no effect after 15-20 minutes, the oxygen therapy is discontinued.
Recently, higher flow rates of up to 15 liters per minute have shown benefit in individuals who did not respond to the lower flow rates of 7-10 liters per minute. It appears that patients under 50 with episodic cluster headache respond best to oxygen. Not all patients can use oxygen safely, especially those with a history of emphysema.
Oxygen is an attractive therapy because it is safe and easy to use. It can be given in addition to medication for acute and prophylactic treatment of cluster headache. Many cluster patients maintain two oxygen tanks, one at home and one at work. It is very important that the oxygen be administered correctly (e.g., no nasal cannula) or it will not be effective. Drawbacks to oxygen use relate to practical issues such as:
- Immediate access to oxygen all the time
- Restrictions required by fire departments in various locations
Triptans
Two types of triptan drugs are effective for treatment of cluster headache, sumatriptan and zolmitriptan.
Sumatriptan (injectable or subcutaneous) is the drug of choice since it is the most effective medication for the acute relief of an individual cluster headache. Sumatriptan belongs to a class of drugs known as selective serotonin receptor agonists and causes constriction of cranial blood vessels as well as reduced activity of the trigeminal nerve. Most patients (75-100%) will have complete relief within 15 minutes after administration. For those patients who do not experience complete relief, the severity of the headache is significantly reduced. Patients with chronic cluster headache do not respond to sumatriptan as well as those with episodic cluster headache, and the response time is slower.
The nasal spray formulation of sumatriptan is not as effective as the subcutaneous injection form though some patients report a beneficial effect within 30 minutes of administration of the nasal spray. Sumatriptan tablets taken orally have no role in cluster therapy because by the time the drug takes effect (1 to 2 hours after administration) the headache has usually subsided.
Sumatriptan is a well-tolerated drug and is not associated with any serious side effects. It is known to be safe for patients between the ages of 18 and 65 but knowledge regarding safety and efficacy is limited outside of this age range. It is effective as a short-term as well as longer-term medication and long-term studies indicate that it does not lose efficacy over time. However, there are reports that some patients develop resistance to sumatriptan after taking it for a long period of time and it is no longer effective for them. Although sumatriptan is very effective in aborting an existing attack, it is not effective in preventing an imminent attack (prophylactic therapy).
Contraindications for sumatriptan include:
- Ischemic heart disease (e.g., angina pectoris)
- Arterial hypertension (high blood pressure)
- Past history of stroke
There are limits regarding dosages for sumatriptan administration (e.g., it is usually not recommended to be taken more than twice a day). Patients who use high doses of sumatriptan over a prolonged period of time should be monitored for electrocardiographic and other changes.
Patients who may not benefit from sumatriptan and who may need to consider alternative treatment for cluster headache include:
- Two or more headaches a day
- Contraindications or adverse effects to sumatriptan
- Chronic cluster headaches or headaches for extended periods of time
- Pregnant and nursing women
Zolmitriptan was the first oral triptan (class of drugs effective in treating severe headaches such as migraine and cluster headaches) shown to be effective in cluster headache. Its effect has since been surpassed by use of sumatriptan and oxygen. However, zolmitriptan is an alternative treatment option for patients who cannot tolerate injections, have either failed oxygen therapy, or find it too difficult to use in certain situations. It is slower-acting than sumatriptan and takes up to 30 minutes to take effect.
Corticosteroids
Corticosteroids (e.g., prednisone, dexamethasone) are the fastest acting of the abortive drugs and are also used as a transitional prophylactic medication. Most cluster patients will be headache free while taking corticosteroids. They are effective for patients with episodic cluster headache who may experience a strong reduction or elimination of headaches within 1-2 days of beginning treatment. Corticosteroids are effective for up to 70% of patients with episodic cluster headache and up to 40% of patients with chronic cluster headache.
Because of multiple side-effects that can occur with steroids, these agents are only used for short treatment courses (1 to 2 weeks or less) in patients whose headaches are very severe, intense, and frequent during an episode of cluster headache. The short-term goal of corticosteroids is to suppress headaches immediately until the longer acting preventive drugs become effective which may be up to two weeks.
Unfortunately, if corticosteroids are taken as the only drug, headaches tend to recur when the dosage is reduced below a certain level or completely eliminated. Due to adverse side effects, corticosteroids cannot be used for long-term prophylaxis of cluster headache. Side effects may include:
- Weight gain
- Osteoporosis
- Infection
- Intestinal bleeding
- Hypertension
- Glaucoma
- Fluid retention
Some cluster patients may require 2 or more preventive medications to be combined in order to achieve improvement.
Ergot Alkaloids
Ergot alkaloids are a class of drugs which decrease inflammation and reverse dilation of blood vessels around the brain. They are contraindicated for individuals with peripheral vascular disease. There are two medications in this class which may be used to treat cluster headache:
- Dihydroergotamine mesylate (DHE-45)
- Ergotamine
Dihydroergotamine mesylate (DHE-45) has been used for several decades as an effective abortive agent for acute cluster headaches. When administered intravenously, DHE-45 provides effective relief of cluster headache within 15 minutes. When administered either intramuscularly, subcutaneously, or as a nasal spray, the time to relief is slightly longer. Because cluster attacks may be of short duration and tend to become severe so quickly, it is impractical in that time frame to be able to reach an emergency room to initiate an intravenous drip of the medication. Subcutaneous and intramuscular delivery of DHE-45 are somewhat more suited for self-administration. Even so, this medication does not offer a long-term solution to patients with cluster headache. DHE-45 is most effective in reducing the pain intensity of headaches but does not affect the frequency or duration of the attacks.
Ergotamine has been used for treatment of cluster headache for more than 50 years. It is effective for achieving rapid suppression of cluster attacks. When the cluster episode terminates, ergotamine can be easily discontinued.
Ergotamine is more convenient to use since it can be taken orally and has been reported to prevent nighttime headaches when taken 1-2 hours before retiring for the night.
Ergotamine is contraindicated in patients with:
- Peripheral vascular disease
- Coronary artery disease
- Uncontrolled hypertension
- Pregnancy
Oral or suppository forms of ergotamine used to be the mainstay of cluster abortive therapy but since sumatriptan was introduced, it is not as widely used anymore. The most notable side effects of ergotamine include:
- Arterial spasm
- Dependence with long-term use
Ergotamine cannot be combined with sumatriptan.
Intranasal Lidocaine
Intranasal lidocaine is given as nasal drops or spray and is administered deep in the nostril on the same side as the headache (ipsilateral) in order to block the pain close to the point of origin. Some patients achieve mild to moderate relief within 10 minutes of lidocaine administration but only a few achieve complete relief. Lidocaine is used as an adjunctive (additional or supportive) treatment but not as a stand-alone therapy since it is not as effective as other available medications.
Analgesics
Analgesics are generally not effective since they take a relatively long time to be absorbed into the bloodstream and, therefore, cannot overcome the extreme pain of a cluster headache that intensifies quickly.
In summary, individuals who suffer from chronic cluster headache find the greatest relief from sumatriptan and corticosteroids, however long term side effects of corticosteroids can be very severe so they are administered only for the short-term. Many patients also benefit from oxygen therapy. Chronic cluster headache patients require more aggressive therapy. Some patients reach a point where they need to be admitted to a hospital either for detoxification from all of their medications or, during a particularly difficult bout with unremitting pain, for "heavy-duty" intravenous treatment with drugs such as corticosteroids and ergotamine.
Prophylactic Treatment
It is very important for patients suffering from chronic cluster headache to prevent individual attacks during a cluster episode. It is advisable for all cluster headache patients to take some sort of prophylactic medication in order to reduce their pain and suffering during a cluster headache cycle or episode. When the cluster cycle ends, medication is typically withdrawn. For some individuals who experience many short intense headaches, abortive treatment is difficult to maintain.
The goals of prophylactic treatment include:
- Suppression of headaches
- Maintaining suppression for the expected duration of the cluster episode
- Reduce the frequency, duration, and severity of headaches if it's not possible to suppress them completely
There are several types of prophylactic medications that may be attempted to evaluate and optimize individual efficacy, including:
- Verapamil
- Corticosteroids
- Lithium
- Valproic Acid
- Topiramate
- Methysergide
Verapamil
Verapamil, a calcium channel blocker, is the first-line preventive medication for cluster headache. It is taken orally and is highly effective in reducing the frequency of cluster attacks, though many patients need higher doses than suggested by the manufacturer to obtain relief. It works well for both episodic and chronic cluster headache but prevention of chronic cluster headaches may require a higher dosage than for episodic cluster headaches. Verapamil can be combined with other agents used for cluster headache (e.g., lithium, sumatriptan, ergotamine, and corticosteroids). Since verapmil is so effective, it is also used for continuous treatment for chronic cluster headache.
Verapamil is available in two formulations - regular and extended release. The regular formulation is more effective than the extended release formulation.
Adverse effects of verapamil are not common but may include:
- Bradycardia (slow heart rate)
- Postural hypotension (low blood pressure when changing positions)
- Constipation
- Fatigue
- Edema (water retention)
- Gastrointestinal upset
Monitoring of the heart by electrocardiogram at predetermined intervals is recommended.
Corticosteroids
Prednisone is effective as a prophylactic agent in cluster headache but is given for only limited periods of time since the side effects can be quite significant. Under certain circumstances, for example when the patient cannot obtain relief, the physician may choose to use corticosteroids as a transitional drug until a longer-acting prophylactic medication takes effect.
Lithium
Lithium is still considered a mainstay of cluster preventive therapy and is effective for episodic as well as chronic cluster headache. The positive effects of lithium usually become apparent within a few days of commencing treatment. Long-term effects are not yet known but some patients develop a tolerance for the drug which reduces its efficacy. Lithium may be combined with other medications (e.g., ergotamine or corticosteroids) for severe cluster headache.
Lithium has undergone investigation in several clinical trials and has been shown to achieve good to excellent result in up to 75% of individuals with chronic cluster headache, with some individuals reporting improvement for up to 4 years. Some patients with chronic cluster headache have reported that when they stopped taking lithium, they transitioned from chronic cluster headache to episodic cluster headache. Lithium is reported to be effective in approximately 60% of patients with episodic cluster headache.
The levels of lithium in the blood must be monitored regularly to assess liver, renal, and thyroid function. Lithium is associated with several side effects including:
- Diarrhea
- Tremor
- Polyuria (increased production of urine)
- Dehydration
- Hyperthyroidism
- Renal dysfunction
Lithium is contraindicated for individuals taking certain drugs, including:
- Diclofenac
- Indomethacin
- Thiazides
- NSAIDs (nonsteroidal anti-inflammatory drugs)
Valproic Acid
Valproic acid is an anti-seizure drug that has shown efficacy in cluster headache patients in several small trials. It is effective in suppressing attacks in up to 70% of patients and relief is usually achieved within 1-4 days.
It is thought that valproic acid may be particularly helpful for individuals whose cluster headaches are accompanied by migraine-like symptoms (e.g., vomiting, photophobia, and phonophobia).
Adverse effects include:
- Nausea
- Weight gain
- Hair loss
- Lethargy
- Tremor
Topiramate
Topiramate is a newer anti-seizure drug that appears to be highly effective for chronic migraine and shows promise for patients with cluster headache. There have been several small studies showing that when topiramate is administered in fairly low doses, it may turn off cluster headaches within 1 to 2 weeks after starting the medication. In one of these studies, two of the patients on topiramate who achieved remission, suffered from chronic cluster headache. Active investigation of this drug continues.
Although topiramate is usually well tolerated, it can cause side effects so discussion with a physician will be necessary before starting this medication for cluster headache. It is contraindicated in patients with kidney stones. Some of the side effects may include:
- Somnolence (sleepiness)
- Ataxia (loss of coordination)
- Dizziness
- Kidney stones
- Some cognitive impairment
- Weight loss
Methysergide
Methysergide (Sansert) is an ergot alkaloid and is reported to be effective for prophylactic treatment of episodic cluster headache in 20-70% of patients, though data from rigorous clinical trials is not available. Like other ergot alkaloids, methysergide is not intended for long-term prophylaxis and is usually not prescribed for longer than 3-4 months.
Side effects may include:
- Nausea
- Muscle cramps
- Abdominal pain
- Pulmonary fibrosis (following long-term use)
Additional Prophylactic Drugs
There are several other drugs that may be used for prophylactic treatment of patients with cluster headache but which have undergone only limited scientific investigation, including:
- Lamotrigine
- Gabapentin
- Tizanadine
- Methylphenidate
- Baclofen (antispastic drug)
- Clonidine
- Somatostatin
A recent study of octreotide (a somatostatin analog) as an abortive treatment for acute cluster headache showed promising results. To read more about this study, click on the following link:
Pizotifen is commonly used in Europe but is not available in the United States. Studies performed on this drug are limited in number as well as in rigorous control but they indicate that improvement was noted in approximately 50% of participants with cluster headache. Pizotifen appears to be effective for patients with episodic as well as chronic cluster headache. Long-term affects are not well known.
Adverse effects of pizotifen may include:
- Drowsiness
- Increased appetite
- Weight gain
When faced with a decision regarding prophylactic treatment for cluster headache, verapamil is typically the medication of first choice. Doses are slowly increased until the medication takes effect. In the intervening time period, the physician may opt to prescribe corticosteroids, ergot alkaloids, or triptans which are faster acting than verapamil. When an individual medication is not sufficiently effective, the physician may choose to combine two or more drugs for enhanced effect.
When cluster headache does not respond to treatment, it is called refractory cluster headache. Approximately 10-20% of individuals suffering with cluster headache do not respond to first or second-line medication. Some small studies indicate that pizotifen and valproic acid may have a limited effect refractory cluster headache.
Alternative Agents
In addition to the medications mentioned above, there are other agents that have gained popularity due to their effectiveness in relieving cluster headache although they have not been approved by the US Food and Drug Administration for treatment of cluster headache. These include:
- Melatonin
- Capsaicin/Civamide
- Botulinum Toxin A
Melatonin
Melatonin is a hormone that is naturally produced by the body and is actively involved in the sleep cycle. It is the most reliable marker of the circadian rhythm in humans. For unknown reasons, serum levels of melatonin are lower than normal in patients with cluster headaches between cycle periods and, even more so, during a cluster attack. The possibility arises that the reduced level of melatonin may be associated with the development of cluster headache.
Several studies have recently shown that fairly large doses of melatonin can stop cluster attacks. Small clinical trials have shown that approximately 50% of patients with cluster headache taking melatonin achieved remission within 3-5 days. However, the efficacy of melatonin is still a subject of debate, especially for the treatment of refractory cluster headache.
Melatonin can be purchased over-the-counter and appears to have minimal side effects. As yet no specific brand of melatonin can be suggested, although if one brand does not appear to be helping, trying another brand of melatonin may be worthwhile. No one can be sure how much melatonin is actually in each pill or capsule that is sold on the market because melatonin is not regulated by the U.S. Food and Drug Administration. Before starting melatonin, a physician should be consulted.
Capsaicin and Civamide
Capsaicin is a substance found in chili peppers and, when extracted and used medicinally, acts as a neurotransmitter depletory, meaning that it depletes neurotransmitters from the nerve endings which leads to a loss of sensation. Intranasal capsaicin, when administered on the same side as the cluster headache, is effective in aborting the attack but its use is severely limited due to the significant burning and irritation of the tissue that occurs when it is applied. Small trials report that up to 60% of patients participating in those studies found relief from pain.
Civamide is a synthetic form of capsaicin and achieves the same effects with less intense burning and irritation. It is administered intranasally to patients with cluster headache. Though civamide is more promising in terms of comfort, results of efficacy from limited studies have been mixed. Some patients respond initially with a reduction in the number of headaches but after 3 weeks, the drug seems to be less effective.
Botulinum Toxin A
Botulinum toxin A has been widely studied for the treatment of various types of headache and chronic pain, including cluster headache. Most of the studies were not controlled studies, meaning that there was no control group for comparison, but reports of pain relief for some patients are encouraging. The mechanism of relief is not well understood. Current information suggests that botulinum toxin A is safe to use. Further multicenter, randomized and controlled studies are needed. If you are interested in more information on treatment with botulinum toxin A, please click on the following link: