Cluster Headache Treatment & Management

Pharmacologic management of cluster headache (CH) may be classified into 2 general approaches as follows:

• Abortive/symptomatic (eg, oxygen, triptans, ergot alkaloids, and anesthetics)

• Preventive/prophylactic (eg, calcium channel blockers, mood stabilizers, and anticonvulsants)

Olanzapine ^[15] and kudzu ^[16] have also been used to treat CH, but their effectiveness has not been determined. Antihistamines, such as chlorpromazine, do not appear to be helpful in relieving CH symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be given for pain relief.

Galcanezumab is the first drug to gain FDA approval for decreasing the frequency of episodic cluster headaches. ^[17]  

Various procedures may be performed on trigeminal nerve or autonomic pathways, including alcohol injections and section or avulsion of nerves for chronic refractory cases. Surgical treatment may be initiated if the patient has contraindications to medications or if medications are not effective; it is employed only in strictly unilateral cases. Radiofrequency (RF) thermocoagulation of the trigeminal ganglion has had promising results in some patients with intractable pain.

Treatment guidelines are available from the American College of Emergency Physicians, the National Headache Foundation, and Institute for Clinical Systems Improvement. ^{[18, 19, 20]} Neurologic consultation may be useful if the diagnosis is in doubt or for management of difficult cases.

Management of pregnant patients

CH is rare during pregnancy, but when it does occur, episodes tend to have the same character and severity as in nonpregnant patients. ^[21] Treatment options for pregnant women are poorly documented. The first line of treatment is pure oxygen via a nonrebreather mask (see image below). Triptans and ergot alkaloids should be avoided. The use of selected preventive medications, which are rated pregnancy category B, should be discussed thoroughly with the patient and her obstetrician. ^[22]

Galcanezumab is the first drug to gain FDA approval for decreasing the frequency of episodic cluster headaches. In a phase trial (n=106), galcanezumab showed a mean of 8.7 fewer weekly cluster headache attacks compared with 5.2 fewer with placebo. A higher percentage of patients responded to galcanezumab (71.4%) compared with placebo (52.6%). ^[17] After a single SC loading dose, galcanezumab is administered once monthly until the cluster period ends.

Abortive agents are given to stop or reduce the severity of an acute CH attack, whereas prophylactic agents are used to reduce the frequency and intensity of individual headache exacerbations. In view of the fleeting, short-lived nature of the attacks, effective prophylaxis should be considered the cornerstone of management. The prophylactic regimen should start at the onset of a CH cycle and continue until the patient is headache-free for at least 2 weeks. The agent then may be tapered slowly to prevent recurrences.

Abortive agents

Oxygen (8 L/min for 10 minutes or 100% by mask) may abort the headache if used early. ^{[23, 24]} The mechanism of action is unknown.

5-Hydroxytryptamine-1 (5-HT₁) receptor agonists, such as triptans or ergot alkaloids with metoclopramide, are often the first line of treatment. Stimulation of 5-HT₁ receptors produces a direct vasoconstrictive effect and may abort the attack.

The triptan that has received the most study in the setting of CH is sumatriptan. ^{[19, 23, 24]} Subcutaneous injections can be effective, in large part because of the rapidity of onset. Studies have indicated that intranasal administration is more effective than placebo but not as effective as injections; there is no evidence that oral administration is effective. A typical dose is 6 mg subcutaneously, which may be repeated in 24 hours. Nasal spray (20 mg) may also be used.

Other triptans that may be considered for abortive treatment of CH are zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan. In addition, researchers have begun to explore the possibility of using triptans for prophylaxis of CH. ^[25]

Dihydroergotamine can be an effective abortive agent. It is commonly given intravenously (IV) or intramuscularly (IM) and may be self-administered; it can also be given intranasally (0.5 mg bilaterally). ^[24] Dihydroergotamine tends to cause less arterial vasoconstriction than ergotamine tartrate and is more effective when given early in a cluster attack.

Parenteral opiates may be used if relief is inadequate. The short-lived and unpredictable character of CH precludes effective use of oral narcotics or analgesics, though oral regimens may sometimes be helpful for residual soreness. Abuse potential does exist. Narcotics are not generally recommended for aborting CH.

Intranasal civamide and capsaicin have yielded good results in clinical trials. Application of capsaicin to the nasal mucosa led to a clinically significant decrease in the number and severity of cluster headaches; nasal burning was the most common adverse effect.

Intranasal administration of lidocaine drops (1 mL of a 10% solution placed on a swab in each nostril for 5 minutes) is possibly helpful; however, it requires a specific and, for many patients, difficult technique.

Prophylactic agents

Calcium channel blockers may be the most effective agents for CH prophylaxis. ^[24] They can be combined with ergotamine or lithium. Of the calcium channel blockers, verapamil may be the most useful, though others, including nimodipine and diltiazem, have also been reported to be effective.

Lithium has been suggested as an option because of the cyclical nature of CH, which is similar to that of bipolar disorders. It effectively prevents CH (particularly in its more chronic forms) ^[26] and treats bipolar mood disorder, another cyclic illness. Responses vary (with chronic CH patients generally being more responsive), but lithium is still a recommended first-line agent for CH. There is a tendency for the effect to wane after dramatic relief is seen in the first week.

Methysergide, though no longer available in the United States, is very effective for episodic and chronic CH prophylaxis. It can often reduce pain frequency, particularly in younger patients with episodic CH. If it yields no improvement after 3 weeks, it is unlikely to be beneficial. It should not be given continuously for longer than 6 months; a drug-free interval of 3-4 weeks must follow each 6-month course.

A few relatively small controlled studies have found anticonvulsants (eg, topiramate and divalproex) to be effective in the prophylaxis of CH, though the mechanism of action remains unclear.

Corticosteroids are extremely effective in terminating a CH cycle and in preventing immediate headache recurrence. High-dose prednisone is prescribed for the first few days, followed by a gradual taper. Simultaneous use of standard prophylactic agents (eg, verapamil) is recommended. The mechanism of action in CH is still subject to speculation.

Tricyclic antidepressants are more helpful as prophylaxis of other headache syndromes. Beta blockers may worsen bradycardia occurring during the cluster attack.

Various invasive nerve blocks and ablative neurosurgical procedures (eg, percutaneous RF ablation, trigeminal gangliorhizolysis, and rhizotomy) have been implemented successfully in cases of refractory cluster headache (CH).

Percutaneous RF ablation may achieve success in 50% of patients, with fair-to-good results in 20% and failure in about 30%. Side effects include facial dysesthesia, corneal sensory loss, and anesthesia dolorosa. Gamma-knife radiosurgery is a less invasive alternative for pervasive CH but is associated with a significantly increased risk for facial sensory disturbances. ^[27] Botulinum toxin injections to manage CH have produced limited success. ^[28] Greater occipital nerve block may be beneficial in aborting CH. ^{[15, 29]}

Deep brain stimulation with implantation of stimulating electrodes under stereotactic guidance into the ipsilateral posterior inferior hypothalamus is another potential option for chronic CH refractory to pharmacologic therapy. ^{[30, 31, 32, 33]} This technique is invasive and is associated with significant risk of complications, including intracranial hemorrhage. ^[34] Other serious side effects are subcutaneous infection, micturition syncope, and transient loss of consciousness. ^[35]

Stimulation of the sphenopalatine ganglion, which is located in the pterygopalatine fossa, may also be considered. ^[36] This approach has shown effectiveness in select patients with chronic CH. ^[37]

In 2017, the FDA approved a hand-held device to treat cluster headaches. ^[38] The non-invasive device works by transmitting mild electrical stimulation to the vagus nerve through the skin on the neck. Approval was based on 2 clinical trials (ACT1 and ACT2) showing that the device was more effective than placebo in reducing cluster headache pain. ^[39]

To prevent cluster headache (CH), the patient should avoid known headache triggers to the extent possible. For example, disturbances in the sleep cycle can induce attacks. Strong emotions and excessive physical activity may also induce attacks.

Tobacco may slow responsiveness to medications. Narcotics may expedite transformation of episodic CH to chronic CH.