Which Treatments Are Effective Against Intractable Cluster Headache?

ASHEVILLE, NC—Patients with intractable cluster headache present an urgent challenge to neurologists. The disorder is associated with “the worst pain you can experience,” and most patients have suicidal ideation, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. To help these patients, it is necessary to confirm the diagnosis, conduct proper evaluations for secondary mimics, and choose the most appropriate and effective treatments, he said at the Eighth Annual Scientific Meeting of the Southern Headache Society.

Making the Diagnosis

The current diagnostic criteria for cluster headache include severe unilateral orbital, supraorbital, or temporal pain that lasts for 15 minutes to 180 minutes when untreated. Patients may have conjunctival injection, lacrimation, rhinorrhea, or a sense of restlessness. Most patients have between one and three attacks per day, and the average attack lasts from 60 minutes to 75 minutes, said Dr. Rozen. Migrainous features such as photophobia, phonophobia, and nausea are common in cluster headache, but should not affect the diagnosis. If the duration and frequency of attacks are consistent with cluster headache, then that is the correct diagnosis, said Dr. Rozen.

Like migraine, cluster headache may be episodic or chronic. Episodic cluster headache is more likely to remit than chronic cluster headache, but the former may transition to the latter.

The European Headache Fed­er­ation has defined treatment-refractory cluster headache as cluster headache that fails to respond to more than three typical preventive medicines. Regardless of whether the disorder is episodic or chronic for a given patient, it may become intractable, said Dr. Rozen.

Reasons for Intractability

One potential reason for intractability is an incorrect diagnosis. Cluster headache is a trigeminal autonomic cephalalgia (TAC), and a person with a diagnosis of intractable cluster headache may in fact have a different TAC. The TACs form a spectrum, and a patient’s disorder may change from cluster headache to paroxysmal hemicrania, for example, said Dr. Rozen. “Always think of [attack] duration and frequency to make your diagnosis.”

Another potential reason for intractability is that the headache is secondary to a lesion. The secondary headache disorders often mimic the primary headache disorders, but do not respond to typical medications. The three most common causes of secondary cluster headache are secretory pituitary tumors, carotid dissections, and cavernous sinus lesions. “Every cluster patient … deserves a brain MRI with or without the pituitary cuts, an MR angiogram (both head and neck with dissection protocol), and pituitary hormones,” said Dr. Rozen.

Established and Emerging Acute Treatments

The most common acute treatments for cluster headache are sumatriptan injection or nasal spray and high-flow oxygen. Most patients respond to these treatments, but for those who do not, neurologists may consider options such as dihydroergotamine (DHE) injection, ergotamines, intranasal lidocaine, olanzapine, chlorpromazine suppository, and indomethacin suppository. Data from the US Cluster Headache Survey, however, indicate that less than 45% of patients respond to these treatments.

Most patients with cluster headache do not respond to oral acute medications because they have slow onsets of action. An exception is zolmitriptan, which is administered in a 10-mg dose, as opposed to the traditional 5-mg oral dose. Another acute nonmedicinal therapy is a suboccipital nerve block, which often terminates a headache within a minute, said Dr. Rozen.

In addition, new acute treatments for cluster headache have emerged. One is the delivery of oxygen by demand valve, which provides oxygen according to the user’s respiration rate and tidal volume. Unlike previous delivery methods, which deliver a small amount of ambient air, the demand valve delivers 100% pure oxygen. The demand valve also allows hyperventilation, which may be crucial for effective treatment, said Dr. Rozen. Several studies have suggested that demand-valve oxygen may be more effective than the typically prescribed continuous-flow oxygen administered through a nonrebreather face mask.

In 2017, the FDA cleared gamma­Core, a noninvasive vagus nerve stimulation (VNS) device, for the acute treatment of episodic cluster headache. Patients can use the device to deliver two-minute doses of stimulation through a conductive gel applied to the neck. The treatment may be considered for patients who have not responded to other acute medications, said Dr. Rozen.

In a study by Schoenen and colleagues, 67% of patients with chronic cluster headache who were treated with on-demand sphenopalatine ganglion stimulation achieved pain relief. In comparison, 7% of patients who received sham treatment achieved pain relief. Sphenopalatine ganglion stimulation is not approved in the United States, however.