Cluster Headache Treatments In conventional medicine perspective

Cluster Headache
Cluster Headache also known as suicide headache, is defined as an uncommon distinctive neurovascular syndrome occurring in either episodic or chronic patterns of that occur periodically over a long period of time. The diseases affects over 0.1% of the population, occurring at 45-to 60-day intervals with one to three headaches a day lasting 45 min to 2 h(a), if untreated it, can cause increased frequency of the attacks.
Treatments
A. In conventional medicine perspective
A.1. Non medical treatment
1. Testosterone replacement therapy 
Women and men with abnormal testosterone levels causes of cluster headache may be treated with Testosterone replacement therapy. In the study conducted by Department of Neurology, Cleveland Clinic Foundation, abnormal testosterone levels in patients with episodic or chronic cluster headaches refractory to maximal medical management may predict a therapeutic response to testosterone replacement therapy. In the described cases, diurnal variation of attacks, a seasonal cluster pattern, and previous, transient responsiveness to melatonin therapy pointed to the hypothalamus as the site of neurological dysfunction(27)

2. Melatonin as adjunctive therapy
The use of melatonin as adjunctive therapy has been reported in patients with cluster headache who have incomplete relief of their headaches on conventional therapy. In the study by Montreal Neurological Institute, McGill University, patients with chronic cluster headache or patients with episodic cluster headache whose headaches are uncontrolled on conventional therapy do not appear to gain therapeutically from the addition of melatonin to their usual treatment regimens. It is perhaps the phase-shifting properties of melatonin that mediate its effect in patients with episodic cluster headache, and it may be necessary to treat from the beginning of the cluster bout to reset the circadian pacemaker, thus producing a more positive outcome(28)

3. Glucocorticoid therapy
Glucocorticoid therapy has been a well-recognized abortive treatment for cluster headaches.  In the study conducted by Department of Neurology, The Cleveland Clinic Foundation, Accumulated evidence suggests sympathetic dysfunction--embodied in the Horner sign so commonly seen in the cluster headache--as a necessary ingredient in the inception of the cluster headache. Sympathetic dysfunction now is thought to be associated with the hypercortisolism, hypotestosteronism, and lower-than-normal melatonin levels in the active cluster patient. Future research may hold the key to a fuller explanation of the complex interaction of hormonal systems in the cluster headache(29)

4. Oxygen therapy 
Oxygen therapy has been well known to be used in treating cluster headache. Hyperbaric oxygen therapy (HBOT)was effective for the termination of acute migraine in an unselected population, and weak evidence that NBOT was similarly effective in cluster headache. Given the cost and poor availability of HBOT, more research should be done on patients unresponsive to standard therapy. NBOT is cheap, safe and easy to apply, so will probably continue to be used despite the limited evidence in this review(31)

5. Etc.

A.2 Surgical treatment
If Chronic cluster headache, also known as chronic migrainous neuralgia, is unresponsive to medical treatment. Surgical treatment may be another choice as some researchers suggested that trigeminal ablative procedures might have a dual role in the relief of medically intractable cases, by directed against either the trigeminal nerve or the nervus intermedius/greater superficial petrosal (NI/GSP) pathway. Among 26 patients who underwent posterior fossa trigeminal sensory rhizotomy or percutaneous radio-frequency trigeminal gangliorhizolysis at our institution, relief of pain was excellent in 14 (54%), fair to good in 4 (15%), and poor in 8 (31%)(32). AS Trigeminal operative procedures are not consistently helpful in chronic cluster headache, while NI section has been shown to give potentially long lasting relief but carries the potential risks of cerebellopontine angle surgery(33)

A.3. Medication
A.3.1. Preventive medicine
1. Prophylactic medicines
a. Calcium channel blocker (Verapamil) 
European guidelines suggest the use of calcium channel blocker verapamil the at a dose of at least 240 mg daily. In the study of higher doses conducted by Pôle Neurosciences Cliniques du CHU de Nice, CH patients treated with verapamil VHD (≥720 mg) were considered with a systematic electrocardiogram (EKG) monitoring. Among 200 CH patients, 29 (14.8%) used verapamil VHD (877±227 mg/day). Incidence of EKG changes was 38% (11/29). Seven (24%) patients presented bradycardia considered as nonserious adverse event (NSAE) and four (14%) patients presented arrhythmia (heart block) considered as serious adverse event (SAE). Patients with EKG changes (1,003±295 mg/day) were taking higher doses than those without EKG changes (800±143 mg/day), but doses were similar in patients with SAE (990±316 mg/day) and those with NSAE (1,011±309 mg/day). Around three-quarters (8/11) of patients presented a delayed-onset cardiac adverse event (delay ≥2 years). Our work confirms the need for systematic EKG monitoring in CH patients treated with verapamil. Such cardiac safety assessment must be continued even for patients using VHD without any adverse event for a long time.(59)

b. Side effects are not limit to
* Dizziness
* Fatigue
* Headache and lightheadedness
* Redness, or swelling at the injection site
* allergic reactions, such as as rash, hives; itching, in some cases difficulty breathing
* Irregular heartbeat
* Etc.

2. Steroids 
a. Steroid such as prednisolone/prednisone, are also effective, but patient may have to take the medicine with a high dose  in longer time up to 6 months, but recurrence is frequent and may lead to steroid-dependency. Some researchers found that a single suboccipital steroid injection completely suppresses attacks in more than 80% of CH patients. This effect is maintained for at least 4 weeks in the majority of them(60)
b. Side effects
*  Orally ingested steroids can affect the liver and in severe case can cause liver damage
*  Steroids can increased levels of LDL
* leading to increased level of estrogen
* It can cause acne
* Etc.

3. Anticonvulsants such as topiramate
a. Anticonvulsants or anti seizure are medication used to treat epileptic seizures, bipolar disorder as mood stabilizers and neuropathic pain. In the study conducted by Department of Neurology, Canisius Wilhelmina Ziekenhuis, anticonvulsants, considered as a class, reduce migraine frequency by about 1.3 attacks per 28 days compared with placebo, and more than double the number of patients for whom migraine frequency is reduced by > or = 50% relative to placebo.(68)
b. Side Effects are not limit to
1. The medication may also increase central nervous symptoms such as dizziness, drowsiness, unsteadiness, feeling dull difficulty concentrating, focusing, mood swing, etc.
2. The medicine may cause gastrointestinal discomfort such as nausea, and vomiting.
3. Other side effects include liver or kidney damage and decrease the amount of platelets in your blood
4. Etc.

4. Beta-blocker (usually propranolol [Inderal] or timolol [Blocadren])
a. Beta-blocker are also known as beta-adrenergic blocking agents, use to block norepinephrine and epinephrine from binding to beta receptors on nerves to prevent migraine headache. Some researchers suggested that the addition of combined β blocker plus behavioural migraine management, but not the addition of β blocker alone or behavioural migraine management alone, improved outcomes of optimised acute treatment.(65)
b. Side effects are not limit to
b.1. Beta-blocker may interact with other medicines, such as thioridazine, chlorpromazine, etc.
b.2. Most common side effects include dastrointestional discomfort such as stomach cramps, nausea and vomiting.
b.3. The medication may also increase nervous symptoms, including headache, depression, confusion, dizziness, etc.
b.4. Etc.

4. Other preventive treatment
a. Methysergide
Methysergide interacts with serotonin (5-HT) receptors in treating migraine headache. In the study posted in European Journal of Neuroscience suggested the support of the hypothesis that 5-HT_2B receptors located on endothelial cells of meningeal blood vessels trigger migraine headache through the formation of nitric oxide (61), but with certain side effects, including Nausea, vomiting, diarrhea, dizziness, drowsiness, stomach upset, heartburn, etc.

b. Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements and use to to treat and prevent episodes of mania in people with bipolar disorder. In a review of the use of Lithium treatment of chronic cluster headaches, administered lithium carbonate to two patients whose cluster headaches had brought them to the point of contemplating suicide. Both patients responded quite dramatically. Case 1 has now been virtually free of headaches for over two years and Case 2 has been in remission for over twelve months(62) vut with certain side effects, ivluding restlessness, loss of appetite  stomach pain or bloating, indigestion, weight gain or loss, dry mouth, etc.

c. Intravenous magnesium sulfate 
The treatment is effective for cluster headache in patient with Low Serum Ionized Magnesium Levels, but some researcher sugested that regardless of the ionized magnesium level. Measurements of ionized magnesium may prove useful in elucidating the pathogenesis of cluster headache and in identifying patients who may benefit from treatment with magnesium.(63). Intravenous magnesium sulfate  may not suitable to Patient with kidney disease.

d. Melatonin
In a study conducted by Thomas Jefferson University Hospital, reported that a lack of melatonin secretion may predispose the cluster sufferer to nocturnal and, possibly, daytime attacks. Leone et al. demonstrated that melatonin could rapidly alleviate cluster attacks, but only in episodic cluster patients. We report two chronic cluster headache patients who had both daytime and nocturnal attacks that were alleviated with melatonin.(64)

A.3.2. Medication to relieve symptoms during an attack
Depending to the severity of the disease, acute attacks may be best prescribed by a prescription version of an NSAID, of which have a potent vasoconstricting action (constricting blood vessels) and patients are instructed to take them during or at the onset of a cluster headache. including
1. Triptan
a. Triptan are a family of tryptamine-based drugs used in the treatment of migraine headache and cluster headache. In the comparison of subcutaneous sumatriptan and oral administration formulation, subcutaneous formulation has a faster time of onset and high rate of efficacy when compared with the oral formulation, but the oral formulation appears to be better tolerated.(67)
b. Side effects of Triptan are not limit to
b.1. Nausea
b.2. Dry mouth
b.3. Tingling
b.4. Burning,
b.5. Dizziness
b.6. Drowsiness
b.7. Warm or cold sensations
b.8. Feelings of heaviness, pressure, or tightness
b. Other severe symptoms include coronary spasm, heart disease, shortness of breath, changes in vision, etc.

2. Ergotamine
Ergotamine has been used to treat migraine for a century and is still considered to be the most effective therapeutic agent for acute attacks andt good responses of the medication are associated with plasma concentrations of 0.2 ng/ml or above within one hour of administration.
In the same study, researchers also emphasized the principal adverse effects of ergotamine include nausea, vomiting, weakness, muscle pains, paraesthesiae and coldness of the extremities and suggested dosage must therefore be limited to no more than 10mg per week to minimise toxicity.(66)

3. Etc.
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Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/18047865 
(27) http://www.ncbi.nlm.nih.gov/pubmed/16732838
(28) http://www.ncbi.nlm.nih.gov/pubmed/12390642
(29) http://www.ncbi.nlm.nih.gov/pubmed/16539869
(30) http://www.ncbi.nlm.nih.gov/pubmed/17257239
(31) http://www.ncbi.nlm.nih.gov/pubmed/18646121
(32) http://www.ncbi.nlm.nih.gov/pubmed/2423815
(33) http://www.ncbi.nlm.nih.gov/pubmed/2401621 
(53) http://www.ncbi.nlm.nih.gov/pubmed/18783445
(54) http://www.ncbi.nlm.nih.gov/pubmed/20425031
(55) http://www.ncbi.nlm.nih.gov/pubmed/21197315
(56) http://www.ncbi.nlm.nih.gov/pubmed/22426836
(57) http://www.ncbi.nlm.nih.gov/pubmed/2948651
(58) http://www.ncbi.nlm.nih.gov/pubmed/10998643
(59) http://www.ncbi.nlm.nih.gov/pubmed/21258839 
(60) http://www.ncbi.nlm.nih.gov/pubmed/16202532
(61) http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.1996.tb01583.x/abstract
(62) http://www.ncbi.nlm.nih.gov/pubmed/737393
(63) http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.1995.hed3510597.x/abstract
(64) http://www.ncbi.nlm.nih.gov/pubmed/11843873
(65) http://www.ncbi.nlm.nih.gov/pubmed/20880898
(66) http://www.ncbi.nlm.nih.gov/pubmed/18454787