Cluster Headaches and Treatment Update

Lawrence Robbins,M.D.*

Summary of cluster headache characteristics and update on abortive and preventive treatments.

Cluster headache is among the most severe pains known to mankind. It is characterized by excruciating, debilitating pain lasting from 15 to 180 minutes, or occasionally longer. The pain is usually located around or through one eye or on the temple. The series of cluster headaches usually lasts several weeks to several months, once or twice per year. Clusters may occur every other year, or even less frequently. Several of the following are usually present: lacrimation, nasal congestion, rhinorrhea, conjunctival injection, ptosis, miosis of the pupil, or forehead and facial sweating. Nausea, bradycardia and general perspiration also occur in many patients. Attacks usually recur on the same side of the head. Cluster headaches tend to occur more in spring and fall. There is usually no family history of cluster headache, but occasionally there is such a family history.

Specific Characteristics of Cluster Headaches

Males are afflicted more than females by a 2.5 to 1 ratio. The onset of the clusters is usually between the age of 20 and 45, but there are many cases of clusters in teenagers and occasionally clusters begin in the 50s or 60s and rarely in the 70s. Women tend to have an older age of onset for their cluster headaches than men. Occasionally a brief aura may occur. The prevalence is 0.4% of the population.

The pain of the cluster attack is extreme and starts very quickly, usually without an aura or a warning. Within minutes, it becomes very severe. Although the pain is usually located about the eye or temple, it may be more intense in the neck or facial areas. Although usually unilateral, the pain changes sides in 10% to 15% of patients—either during a cluster cycle or the next cycle may see pain on the opposite side. The pain itself is excruciating, described in various manners as sharp, stabbing—“like my eye is being pulled out” and occasionally, throbbing.

The length of attack varies, but 45 minutes is the average. Cluster patients usually experience one or two headaches per day, but this may increase to as many as seven per 24 hours or decrease to as little as one or two per week. They usually occur around the same time each day, with the time period 9 pm to 10 am being the most frequent. Approximately half of the patients awaken from sleep with the headaches.

Cluster cycles, except in the chronic variety, usually last 3 to 8 weeks and then stop until the next bout of clusters. The clusters occasionally last as little as several days, or as long as 5 months at which time we begin to think that they may have converted to the chronic cluster type. Ten percent of cluster patients have chronic clusters in which there is no break of at least six months between attacks. One or two bouts of the clusters per year is average for most patients. They may increase in frequency with only several months in between bouts or several years may elapse between attacks. When periodic clusters begin at older ages, the chance of conversion to chronic cluster becomes greater. The natural history of clusters is not known, but the tendency is for the cluster series to stop at a certain age. Many patients “lose” their clusters in the late 30s or 40s, particularly if they have had them for many years.

During the cluster series, over half of the patients are very sensitive to alcohol and most patients will have an attack triggered by ingestion of alcohol. The other ‘headache foods’ are less important, but avoiding MSG, aged cheeses and meats, and chocolate is prudent during the cluster series. MSG, in particular, seems to trigger a more sever cluster in some patients. Cluster patients may have their clusters after stress is over and occasionally excessive cold, heat, or bright light have been associated with the precipitation of a cluster. However, most cluster patients have very little control over the clusters, except with medication.

The typical episodic cluster series builds over one to two weeks and peaks for one to three weeks and then decreases. In the 10% of cluster patients with chronic clusters, periods of peaks and valleys with the headaches also occur but an extended break without any clusters is not present. Chronic clusters are not usually consistent throughout the year but tend to increase in certain seasons. In managing the clusters, we keep in mind the fact that the clusters build and then peak so that I often treat them with somewhat less medication—particularly corticosteroids—in the beginning of a cluster period. The natural history of clusters is unknown. However, it appears as if the more years a patient has them, the more likely they are to abate.

Non-Medication Treatment of Cluster Headache

Other than medication, very little is available for sufferers of cluster headache. The pain is too severe for relaxation methods and some patients state that biofeedback or relaxation may actually precipitate or increase a cluster. However, learning simple deep breathing techniques or relaxation methods does aid some patients in helping to curb the anticipation of the cluster attacks. Much anxiety is generated during the day when the patient knows that nighttime brings intense, excruciating pain.

Icing the area of pain may help, although sometimes heat will be more effective. Some patients let the shower run hot water on their cervical area, or they use a shower water massage apparatus to allow the hot water to run over their cervical or frontal area. Pressing over the temporal area with moderate pressure is occasionally helpful. Cluster patients usually feel better when moving about during an attack. They tend to be active (such as pacing) as opposed to the quiet sought by migraineurs.

Medications For Cluster Headache

For most patients, both abortive and preventive medications are helpful and only in a minority of situations do we simply use abortive medicines.

The abortive treatment for clusters is the same for episodic and for chronic cluster headaches. Since the headache is very intense from the beginning and the pain is severe and excruciating, medication to aid the attack must act quickly. Most cluster attacks last less than one hour, averaging about 45 minutes, and thus oral pain medication is only of limited value. However, in patients whose attacks do last for more than one hour, pain medications may be useful—particularly if the standard cluster abortives are not completely effective. Anti-emetics are also used for those patients with nausea, and the sedative effect of these is often helpful.

First-Line Cluster Abortive Medications

The first line abortive cluster medications are as follows:

Inhaled oxygen(higher flow rate is much more effective)
Sumatriptan injections(3mg and 6mg available)
Imitrex® (sumatriptan generic is available) or Zomig® (zolmitriptan) nasal spray

Oxygen. Oxygen is effective in approximately 70% of cluster headache patients. To obtain a small tank with a mask is relatively easy and not terribly expensive. The tanks are usually rented for one month. If feasible, most patients with cluster headaches should attempt to use oxygen for their attacks. The patient should be sitting with the body leaning slightly forward. A mask is used and 100% oxygen is inhaled at 12 to15 liters per minute. In healthy patients with no pulmonary problems, the oxygen may be inhaled for 15 to 20 minutes. A rebreather mask is helpful.

Sumatriptan Injections. Injectable sumatriptan (Imitrex®, Zembrace=3mg epi-pen device, or the generic: pre-filled syringes, vials(draw up in an insulin syringe), Stat dose system) is generally effective. Sumatriptan pills are more helpful for migraine than for cluster headache, but oral triptans are occasionally adequate. Many patients are reluctant to give themselves injections but, for those who are willing, injected sumatriptan is usually effective—often within minutes—and with a minimum of side effects. Oxygen may be used in conjunction with sumatriptan, and escape pain medication may also be utilized. The new gepants are not indicated for cluster, and generally take too long to become effective.

The dosage of sumatriptan is usually 3 to 6mg given subcutaneously at the onset of the cluster headache. A repeat dose may be given at least one hour after the first injection. Two 6mg injections, or 12mg, is the maximum recommended dosage per 24 hours. Sumatriptan is administered subcutaneously by the use of a convenient auto-injector device. Sumavel™ DosePro™ is a ‘needle-free’ sumatriptan injection. While Sumavel is convenient, it still does sting, and may bruise quite a bit. Also, vials of sumatriptan are available for use with an insulin syringe. By using the vials, the dose may be titrated(some cluster patients only require 3 or 4mg).

Daily use of sumatriptan has not been studied extensively. Thus, until further studies are known, prudent use of sumatriptan would dictate that no more than six injections per week be taken for cluster headache (less for migraineurs).

The side effects of sumatriptan are generally less than those with dihydroergotamine (DHE). Transient pain at the site of injection is common, and ‘icing’ the injection site prior to use may decrease this burning pain. Other side effects include tingling sensations, disturbances of taste, heat flashers, and feelings of pressure or heaviness. Side effects tend to be short lasting. Chest symptoms, flushing, dizziness, and overall weakness may also occur. Minor transient increases in blood pressure have been seen. Nausea is relatively common. Sumatriptan should not be used in children, in pregnant women, in the presence of hepatic or renal impairment, or with cardiovascular disease. Patients over the age of 45 should be screened for cardiac risk factors. The frequent chest pressure that occurs is not usually felt to be of cardiac origin.

Sumatriptan or (Zomig)zolmitriptan nasal spray: while not as effective as the injection for cluster headache, the nasal spray is very convenient and many patients prefer this route of administration. We usually limit the sprays to two per day, but for cluster headaches we will occasionally utilize a third spray as well. Of the two nasal sprays, Zomig nasal spray 5mg is more effective than the sumatriptan spray. There is a 2.5mg Zomig nasal spray available, but the vast majority use the 5mg spray. While not as rapidly effective as the injections, the nasal spray works faster than triptan tablets. Speed is essential in relieving cluster headache, yet occasionally patients prefer the oral triptans.

Second-Line Cluster Abortive Medications

Second line therapies include oral triptans, ergots and dihydroergotamine (DHE), Cambia, ketorolac nasal spray or injections, oral pain medications and intranasal lidocaine.

Oral Triptans. Any of the oral triptans may help, but are usually too slow for cluster headache. Sumatriptan 100mg is the most commonly used oral triptan. The two slow-acting triptans, frovatriptan and naratriptan, are not usually used acutely for clusters. Occasionally, these longer-acting triptans are utilized, mostly at night, to prevent nocturnal clusters.

Ergotamine Tartrate. Strong vasoconstrictors, the ergotamines have many limitations. Ease of administration (they are available as tablets) is a major advantage of the ergots. The frequent side effects of nausea and nervousness limit their use. In older patients, the risk of angina or an actual myocardial infarction restricts its use. The rebound headaches that occur in migraineurs do not seem to be as prevalent a problem in cluster headache patients. The primary ergotamine preparations are generic Cafergot® pills, suppositories and Ergomar® sublingual pills. Peripheral vascular disease or hypertension are contraindications. Ergotamines may exacerbate peptic ulcer disease. The effective dose of ergotamine varies widely among patients. Ergots may be combined with the use of oxygen and other abortive measures but not with triptans.

Ergomar. Tablets contain 2mg of ergotamine tartrate with no caffeine. The usual dose is one pill sublingually at the onset of the cluster attack. Ergomar may also be swallowed and this route may be just as effective as the sublingual method. This may be repeated once in one or more hours and limited to two pills per 24 hours. Nausea is a common side effect as is a bitter or “bad’ taste in the mouth. Nervousness is a frequent side effect, but less so than with Cafergot because there is no caffeine in Ergomar. Ergotamines need to be used with great caution in the presence of hypertension, peripheral vascular disease, or peptic ulcer disease. If chest symptoms occur, ergots should be discontinued.

Generic Cafergot (only generic available). Consists of 1mg of ergotamine tartrate and 100mg of caffeine. Cafergot pills are the most convenient but least effective of the ergots. Dosage is one or two pills at the onset of headache, repeated every two hours as needed, with a maximum of four per day and ten per week. Side effects are similar to the preceding Ergomar discussion, with nausea and nervousness being common. Because of the caffeine, anxiety or nervousness is more common with Cafergot pills than with Ergomar. The same precautions discussed above in the Ergomar section also apply to Cafergot.

Compounded Cafergot Suppositories (only compounded available). These are less convenient but much more effective than the pills. Cafergot suppositories contain 2 mg of ergotamine tartrate and 100 mg of caffeine. The primary side effects are nausea and anxiety. The initial dose is one third or one half of a suppository and then the dose is titrated up or down, depending on the patient’s response. The dose may be repeated after one hour, up to a maximum of two suppositories per day and five per week. Some patients find that as little as one fifth of a suppository is all that they require. Side effects of Cafergot suppositories are the same as those of Cafergot pills. Nausea and anxiety always are limiting factors in the use of ergots.

Compounded Cafergot PB suppositories (only compounded available). These are similar but more effective than plain Cafergot suppositories. Cafergot PB contains 2 mg of ergotamine tartrate, 100 mg of caffeine, 60 mg of sodium pentobarbital, and 0.25 mg of 1-alkaloids of belladonna. Dosage is the same as for the plain Cafergot suppositories. Side effects are decreased, with less nausea and nervousness. Sedation may be a problem, however.

Dihydroergotamine (DHE). This is different from the other ergots in that it is primarily a venoconstrictor rather than an arterial constrictor. Since 1945, there have been relatively few serious side effects reported. DHE is available as an intramuscular (IM) or subcutaneous (SQ) injection or as a nasal spray (Migranal®). The usual dose is 1 mg IM or SQ, or one spray in each nostril to be followed in 10 to 20 minutes by one further spray of Migranal in each nostril. Side effects tend to be minimal with DHE, but nausea, a heat or flushed sensation, nasal stuffiness from the spray, or leg cramps may occur. Occasionally, chest heaviness is also seen. While DHE is not as effective as sumatriptan for cluster headache, DHE at times is the best alternative in patients who may be at some risk for cardiac disease. However, if patients have major risk factors such as uncontrolled hypertension or have known atherosclerotic heart disease, then DHE must be avoided. The usual maximum is three injections per day or two nasal sprays in each nostril per day. A new inhaled form of DHE is expected to be approved shortly. The inhaled form will have better efficacy than the Migranal spray, but not as effective as the injections.

Cambia. Cambia is a powdered form of diclofenac potassium, 50mg. Cambia is FDA approved for migraine. The usual dose is 1 packet(with water, or apple juice) every 2 or 3 hours as needed. GI side effects may limit use. Cambia may be combined with a triptan. Cambia has a quicker onset of action than tablets of nsaids.

Ketorolac nasal spray(Sprix) or ketorolac injections. Sprix is a nasal spray of ketorolac, faster acting than tablets but not as powerful as the injections. Sprix is relatively well tolerated; the usual side effects include a feeling of burning in the throat, and GI side effects. The ketorolac injections, 30 or 60mg, are effective for many migraine and cluster sufferers. GI and renal concerns limit use with ketorolac. Ketorolac should be limited to 6 doses per week. s

The abortive analgesic medications include, among others, the following;

Extra Strength Excedrin®
Butalbital compounds (Fiorinal®, Fioricet, Esgic®, Phrenilin: all are available as generic)
Opioids

In general, we do not want to have cluster patients rely on butalbital or opioids. However, in some refractory patients the pain is so severe and the other therapies are ineffective, justifying the use of butalbital or opioids. The milder approaches, such as Excedrin, should be utilized first, then the butalbital compounds or opioids. While rebound or withdrawal headache is less of a concern with cluster than migraine, we still must try and limit the abortives. At times, this is not an easy task.

Lidocaine spray. There are various devices for SPG blocks(Tian360, Sphenocath) used as a 4% lidocaine solution, the spray has been used since the mid-1980s for cluster headache. I have found it only mildly effective for most patients and almost never adequate by itself. However, intranasal lidocaine does provide sufficient relief to warrant its use. Lidocaine is very safe, with minimal side effects. When used in conjunction with ice and one of the first-line abortives, the lidocaine spray may add 10 to 30% relief.

I put 4% topical lidocaine in a plastic nasal spray bottle. The patient is then instructed to lie in the supine position, extend their head back 30 to 45 degrees, turn the head toward the side of the pain and spray two or three sprays of the lidocaine intranasally. This may be repeated, but I usually limit the lidocaine sprays to six or eight in a 24-hour period. If the nasal passage is blocked, several drops of 0.5% phenylephrine may be used prior to the lidocaine.

Alternatively to the spray bottle, 1 ml of 4% topical lidocaine may be slowly dropped, via a dropper, into the nostril on the side of the pain. Side effects are minimal and may include numbness in the throat or, rarely, nervousness or tachycardia.

Another option for home use is to utilize a TB syringe, with lidocaine, and an atomizer. This is inexpensive.

Preventive Medications(see table 2)

Each cluster patient is unique, with a number of variables determining where we go with medications. If a patient has a short episodic cycle, we may just use abortives, or cortisone plus abortives. For longer cycles we want to initiate one of the usual preventives, such as verapamil. Chronic cluster patients usually require daily medication for most of the year. Most often, we use cortisone(usually Prednisone) for a short period of time, while initiating another preventive, such as verapamil. Prednisone, while usually very effective, should be limited; we want to minimize cortisone side effects. There is some evidence that cluster sufferers may be slightly more prone than others to femoral head necrosis from cortisone.

Comorbidities often determine where we go with medications. If a cluster sufferer is older, smokes, has HTN and reflux, we will be limited as to our medications. Age, GI problems, psychiatric conditions, and previous reactions to medications all contribute to our medication decisions. For those with chronic clusters, we want to utilize medications that have minimal long-term side effects. Table 2 summarizes the usual preventive approaches to preventing cluster headaches. For quick relief, occipital injections with bupivicaine and/or cortisone may be effective. Frontally, the SPG blocks, with bupivicaine, often are helpful for frontal chronic migraine, and cluster headache. They are done via the newer Tx360 device, or the SphenoCath device. SPG blocks, with one of these devices, are very safe, and only take minutes to administer.

Refractory Clusters: For those cluster sufferers who have not found relief with the usual ministrations, a number of approaches have been utilized. Emgality, a monoclonal antibody used for migraine prevention, is now approved for episodic cluster(300mg once per month). Unfortunately, because of the small numbers in limited studies, evidence is lacking for many refractory approaches. These approaches include: stimulants(methylphenidate, mixed amphetamine salts), melatonin, testosterone, SPG blocks, daily opioids, daily triptans(used as a preventive), daily ergots(rarely used), botulinum toxin, and psilocybin, among others. There are several cluster headache support groups, such as Clusterbusters. Clusterbusters runs an excellent annual meeting of cluster headache sufferers.

I have found daily triptans(usually 1 at nite, as a preventive) to be helpful for some patients. The longer-acting triptans, frovatriptan and naratriptan, are usually used for use on a daily basis. SPG blocks are easy to administer with the newer devices(Tx360 and SphenoCath), and used 2 to 4 times weekly they can be very helpful. For some refractory chronic clusters, the implantable ATI SPG stimulator may be very helpful; this is being utilized at several centers in Europe, and studies are ongoing in the U.S. As a last resort, opioids may at least alleviate some of the suffering. Psilocybin(illegal in the U.S.; we cannot advocate its use) has had some research behind it, and has been helpful for some patient

Sample Case History

Richard is a 40-year-old man with a history of 4-week long cycles of cluster headaches, occurring once a year in the fall. The headaches began when he was 35. The cluster period begins slowly, increasing over one week’s time and reaching a peak where Richard has 2 or 3 severe attacks per day. These occur during the night from 10 pm to 3 am. Each cluster attack lasts from 40 to 90 minutes, and the pain is severe. The headache is always on the right side, and is accompanied by eye tearing and nasal congestion.

Treatment Plan

Richard visits our office during the first week into his 4-week headache series. The headaches are increasing in intensity and he is miserable from the pain. At this point, we want to put Richard on a prophylactic regimen, and give him an abortive to help ease the acute attack. We decide to use prednisone, one 20-mg tablet in the morning and another with dinner (40 mg/day) for 4 days. We will reduce this to 20 mg/day after the first 4 days, and then to 10 mg/day after another 6 days. We will then taper off the prednisone entirely over the next 4 to 6 days.

Limiting the amount of corticosteroids is important for two reasons: 1) serious side effects are decreased, and 2) if necessary, we may want to utilize additional prednisone later in the cluster series. If the patient has been on a high-dose of steroids for 3 weeks, we cannot use more corticosteroid. In contrast, by keeping the amount to a minimum, we are able to use steroids later in the cluster period. Cluster sufferers may be more prone to femoral head necrosis with the use of corticosteroids.

With the prednisone, we begin a slow release form of verapamil. This is started at 240 mg/day; we may eventually increase to 2 doses per day, which is generally the maximum (480 mg/day). As the prednisone dose is decreased, and the patient is weaned off the medication, it is hoped that the verapamil will have taken effect.

The use of oxygen as an abortive is discussed with Richard, but he prefers to wait. We give him sumatriptan tablets, 100 mg, as he is reluctant to self-inject sumatriptan. Richard is also instructed to apply ice to the areas of pain. (See Table 2 for list of the most common preventative agents prescribed for cluster headaches.)

Results

Six days later, Richard calls the office. He has had 5 very good days, but as the prednisone is being decreased, the headaches are becoming more severe. Sumatriptan tablets do not help; last night, he had 90 minutes of extremely intense pain. At this point, we convince Richard to try oxygen, at 12 to 15 L/min, as needed, and he rents a tank. Richard also is given sumatriptan injections, 4 mg.

We continue the original plan of decreasing prednisone, and we increase the dose of verapamil to 480 mg/d. We will monitor Richard’s blood pressure. He now has oxygen and sumatriptan injections available as abortive agents; adding lithium or valproate are considerations, as is indomethacin.

I see Richard 4 days later. He is now in his third week of clusters, and by his previous pattern, has 1 to 2 weeks left in the cycle. However, at times a cluster period may exceed the previous one in length, and extended cluster periods of up to several months do occur. Richard states that the oxygen does help his headaches.

The clusters are less severe, but still occur regularly twice at night. Sumatriptan injections stop the attacks within 10 minutes of administration. The verapamil may be having some effect as well. He is down to 20 mg/day of prednisone, and we decide to taper off the dose over the next 4 days. If the headaches increase dramatically, he could return to the prednisone.

Six days later, the headaches are gone, and after a week without headaches, Richard is tapered off the verapamil over the course of 6 days. If the headaches were to return during those 6 days, we would immediately increase the dose of verapamil to the maximum of 480 mg, and consider using prednisone again.

Discussion

It is important to chart which medications are most effective for treating a patient’s cluster headaches, so as to be ready to use them for the next cluster series. I usually write the plan for the next series in the patient’s chart, and inform the patient of the plan.

In Richard’s case, we would use oxygen as an abortive, with injections of sumatriptan. As a preventive, he would be given verapamil, increasing to 480 mg/day, and approximately 2 weeks of prednisone. Instead of the injections, zolmitriptan(Zomig) nasal spray would be a consideration, and occipital nerve blocks are a reasonable possibility. SPG blocks are a strong consideration. Other preventives would include lithium, indomethacin, sodium valproate or topiramate.

Most patients with cluster headaches are prescribed both preventative and abortive therapies. Compared to migraine management, we have relatively few medications that are effective for the treatment of cluster headaches. In order to minimize the use of corticosteroids, it is important to initiate preventive medications early in the cluster cycle. For the typical episodic cluster cycle, we begin medication with the onset of the cluster, and discontinue all medication shortly after the cycle ends. There is no demonstrated utility in continuing medication after the episodic cycle ends. NOTE: This is an updated version of a section from L.Robbins’s book, Advanced Headache Therapy. This discussion is not prescriptive; all medications have side effects, and should not be used without informed consent and a discussion between the patient and physician.

Table 1. Typical Characteristics of Patients with Cluster Headaches

Begins between ages 20 and 45, approximately 0.4% of the population
Male predominance in a 2.5 to 1 ratio
Same time of year with no headache in between the cluster cycles
Primarily nocturnal attacks (but may be anytime)
During cluster cycle, alcohol triggers the headaches
Severe, excruciating, unilateral pain—usually periorbital
Ipsilateral rhinorrhea, lacrimation, conjunctival hyperemia, sweating of the forehead, Homer’s syndrome

Table 2. Common Preventive Medications for Cluster Headaches

NOTE: Emgality, a monoclonal antibody used for migraine prevention, is now approved for the use of episodic cluster headache. The migraine dose is 120mg per month; the dose for clusters is 300mg once per month.

Class/Agent	Dosage	Side Effects	Comments
Corticosteroid: Prednisone	20 to 40 mg/d for 3 to 6 days, then taper off over 4 to 8 days.	Corticosteroids have many adverse effects. When used for short periods of time, the most common side effects are insomnia, gastrointestinal (GI) upset, and anxiety. Serious adverse events have occurred with even short courses of corticosteroids.	Very effective for cluster headache, cortisone is used primarily for episodic cluster headaches. It is given for 1 to 2 week duration during the peak of the cluster series. Additional cortisone may be given later in the cycle, when the cluster headaches increase. Higher doses may be needed when the cluster cycle is peaking in intensity. Due to adverse side effects, it is very important to minimize the use of cortisone.
Calcium Channel Blockers: Verapamil ER	At onset of headache, 240 mg/d or bid—maximum dose 480 mg/d	Constipation. Electrocardiogram (ECG) should be performed because of possible cardiac abnormalities when higher doses are used.	Very effective in episodic and chronic cluster headaches. Often initiated at the onset of the headache, in conjunction with cortisone. Verapamil is then continued while the cortisone is tapered and then stopped. Because of its efficacy and minimal side effects, verapamil is a mainstay of cluster headache prevention.
Lithium	300 mg/d to 900 mg/d	Well-tolerated at low doses; drowsiness, mood swings, nausea, tremor and diarrhea may occur.	Helpful for chronic cluster, and to a lesser degree, episodic cluster headaches. It may be combined with verapamil and/or cortisone. Blood tests need to be performed to assess kidney and thyroid function
Non-steroidal Anti-inflammatory Agents (NSAIDS): Indomethacin	Indomethacin: 25 mg once or bid; up to 75 mg bid or tid.	GI side effects may limit use.	Powerful NSAID, indomethacin can be helpful for some cluster headache patients.
Anti-Epileptic Agents: Sodium Valproate	500 mg/d to 1500 mg/d	May cause weight gain, fatigue, and GI upset, among other side effects.	Valproate and topiramate are occasionally effective against cluster headaches. They are the mainstay of treatment against migraines, but less effective against cluster headaches.
Topiramate	50 mg/d to 200 mg/d	Does not cause weight gain, but cognitive side effects may limit use.
Botulinum Toxin A Injection(only occasionally used)(off label for cluster headache; not as effective as for chronic migraine)	50 to 200 units	Safe, usually no adverse effects; may cause eye droop, or (rarely) generalized weakness.	Botulinum toxin type A FDA-approved for chronic migraine. While the injections are not as effective for cluster headaches, they do help in some patients.
Occipital Injection: Corticosteroid	Triamcinolone: 20 to 40 mg Other forms of injectable steroid have also been utilized.	Steroid injection: local site reaction, or systemic corticosteroid effects (see above).	May decrease cluster headache occurrence for up to 4 weeks.
Bupivacaine	Bupivacaine: 2 to 5 mL)	Bupivacaine: allergic reactions may occur (rare)	May decrease cluster headache occurrence for up to 4 weeks.

Sphenopalatine Ganglion(unilateral on the side of the cluster)

Nerve Blocks(SPG Blocks) Bupivicaine 0.5% Bupivicaine Serial(2 to 4X per week)

allergic rxn(rare) blocks may be effective

Tx360 device or SphenoCath(these are expensive); Or, the patient may do it at home, (VERY INEXPENSIVE) with a TB syringe and atomizer, with 4% lidocaine. We usually demonstrate it in the clinic for the first time. A plastic spray bottle, with lidocaine, may also be utilized.

* Lawrence Robbins is a headache specialist and neurologist north of Chicago. He is an assistant professor of neurology, CMS. Lrobb98@icloud.com