This is the management suggestion from UP To Date, a widely used physician reference:
Verapamil is the agent of choice for the initial preventive therapy of cluster headache. Glucocorticoids may be used adjunctively to help suppress attacks during the initial titration of verapamil or alone when cluster attacks are infrequent and short. (See 'Verapamil' below and 'Glucocorticoids' below.)
Other agents that may be effective include galcanezumab, lithium, and topiramate.
Verapamil — Verapamil is the drug of choice for prophylaxis of episodic and chronic cluster headache [3,43]. Verapamil is usually started at a total daily dose of 240 mg. Both the regular- and sustained-release formulations are useful, but no direct comparative studies are available. Patients treated with regular-release verapamil should receive the total dose in three divided doses a day, while those treated with the sustained-release formulation should receive two divided doses a day.
There are multiple titration methods when treating cluster headache with verapamil:
●We suggest starting at 80 mg three times daily and increasing the total daily dose by 80 mg every 10 to 14 days as tolerated.
●As an alternate titration regimen, verapamil may be initiated with a short course of prednisone. In a short-term treatment trial [44], patients started verapamil at 40 mg three times daily and increased every three days up to a total daily dose of 360 mg. Those additionally assigned to daily prednisone 100 mg for five days and tapering by 20 mg every three days had fewer cluster attacks in the first week than those assigned to placebo (difference -2.4 attacks; 95% CI -4.8 to -0.03).
Most patients respond to a total daily dose of 240 to 480 mg. However, clinical experience suggests that some patients require a total daily dose of up to 960 mg to obtain full prophylactic benefit [1,45]. In an early open label trial, titration up to a total daily verapamil dose of 1200 mg was employed [46]. Thus, an adequate verapamil trial for most patients entails use of a total daily dose of 480 mg to 960 mg before the medication is regarded as a failure. The benefit of verapamil is usually seen within two to three weeks. When the bout is ended, verapamil must not be ended abruptly but should be gradually reduced over two to four weeks depending on the dose and finally stopped.
The use of high-dose verapamil is associated with an increased incidence of electrocardiographic (ECG) abnormalities, including heart block and bradycardia [47,48]. Therefore, an ECG should be obtained after each dose increment above a total daily dose of 480 mg. Some experts recommend getting a pretreatment ECG to screen for baseline cardiac arrhythmia [49].
Other side effects of verapamil include edema, gastrointestinal discomfort, constipation, dull headache, and gingival hyperplasia. However, verapamil is usually well tolerated and can be used safely in conjunction with sumatriptan, ergotamine, glucocorticoids, and other preventive agents.
The efficacy of verapamil for prevention in cluster headache comes from observational experience and some trial data [3,46,50,51]. In one trial of 30 patients, daily verapamil at 360 mg in three divided doses reduced cluster headache attack frequency and analgesic consumption [43]. During the first week of treatment, the median number of daily attacks, the primary outcome measure, was similar for patients treated with verapamil and placebo (1.1 versus 1.7). However, in the second week, the median number of daily attacks was significantly lower for patients treated with verapamil (0.6 versus 1.7). Additionally, only those assigned to verapamil reported a reduction in headache frequency of >50 percent at two weeks (12 of 15 [80 percent] versus 0 of 15)