Blau Joseph N, Engel Hans O
City of London Migraine Clinic, London, UK.
Headache. 2004 Nov-Dec;44(10):1013-8. doi: 10.1111/j.1526-4610.2004.04196.x.
Verapamil is currently the best available prophylactic drug for patients experiencing cluster headaches (CHs). Published papers usually state 240 to 480 mg taken in three divided doses give good results, ranging from 50% to 80%; others mention higher doses--720, even 1200 mg per day. In clinical practice we found we needed to adapt dosage to individual's time of attacks, in particular giving higher doses before going to bed to suppress severe nocturnal episodes. A few only required 120 mg daily. We therefore evolved a scheme for steady and progressive drug increase until satisfactory control had been achieved.
To find the minimum dose of verapamil required to prevent episodic and chronic cluster headaches by supervising each individual and adjusting the dosage accordingly.
Consecutive patients with episodic or chronic CH (satisfying International Headache Society (IHS) criteria) were started on verapamil 40 mg in the morning, 80 mg early afternoon, and 80 mg before going to bed. Patients kept a diary of all attacks, recording times of onset, duration, and severity. They were advised, verbally and in writing, to add 40 mg verapamil on alternate days, depending on their attack timing: with nocturnal episodes the first increase was the evening dose and next the afternoon one; when attacks occurred on or soon after waking, we advised setting an alarm clock 2 hours before the usual waking time and then taking the medication. Patients were followed-up at weekly intervals until attacks were controlled. They were also reviewed when a cluster period had ended, and advised to continue on the same dose for a further 2 weeks before starting systematic reduction. Chronic cluster patients were reviewed as often as necessary.
Seventy consecutive patients, 52 with episodic CH during cluster periods and 18 with chronic CH, were all treated with verapamil as above. Complete relief from headaches was obtained in 49 (94%) of 52 with episodic, and 10 (55%) of 18 with chronic CH; the majority needed 200 to 480 mg, but 9 in the episodic, and 3 in the chronic group, needed 520 to 960 mg for control. Ten, 2 in the episodic and 8 in the chronic group, with incomplete relief, required additional therapy-lithium, sumatriptan, or sodium valproate. One patient withdrew because verapamil made her too tired, another developed Stevens-Johnson syndrome, and the drug was withdrawn.
Providing the dosage for each individual is adequate, preventing CH with verapamil is highly effective, taken three (occasionally with higher doses, four) times a day. In the majority (94%) with episodic CH steady dose increase under supervision, totally suppressed attacks. However in the chronic variety only 55% were completely relieved, 69% men, but only 20% women. In both groups, for those with partial attack suppression, additional prophylactic drugs or acute treatment was necessary.
维拉帕米是目前用于丛集性头痛(CH)患者的最佳预防性药物。已发表的论文通常指出,每日分三次服用240至480毫克可取得良好效果,有效率在50%至80%之间;其他文献提到更高剂量——每日720毫克,甚至1200毫克。在临床实践中,我们发现需要根据个体发作时间调整剂量,特别是在睡前给予更高剂量以抑制严重的夜间发作。少数患者每日仅需120毫克。因此,我们制定了一个逐步稳定增加药物剂量的方案,直至实现满意的控制效果。
通过对每个个体进行监测并相应调整剂量,找出预防发作性和慢性丛集性头痛所需的维拉帕米最小剂量。
连续纳入符合发作性或慢性CH(符合国际头痛协会(IHS)标准)的患者,起始剂量为维拉帕米早晨40毫克、下午早些时候80毫克、睡前80毫克。患者记录所有发作情况,包括发作时间、持续时间和严重程度。根据发作时间,口头及书面告知患者每隔一天增加40毫克维拉帕米:对于夜间发作的患者,首次增加的是晚上的剂量,其次是下午的剂量;当发作发生在醒来时或醒来后不久,建议在通常醒来时间前2小时设置闹钟,然后服药。每周对患者进行随访,直至发作得到控制。在一个丛集期结束时也对患者进行复查,并建议在开始系统性减量前继续服用相同剂量2周。慢性丛集性头痛患者根据需要进行复查。
连续70例患者,52例为发作性CH丛集期患者,18例为慢性CH患者,均按上述方法用维拉帕米治疗。52例发作性CH患者中有49例(94%)头痛完全缓解,18例慢性CH患者中有10例(55%)完全缓解;大多数患者需要200至480毫克,但发作性组有9例,慢性组有3例需要520至960毫克才能控制发作。10例患者缓解不完全,发作性组2例,慢性组8例,需要额外治疗——锂盐、舒马曲坦或丙戊酸钠。1例患者因维拉帕米使其过于疲劳而退出,另1例发生史蒂文斯 - 约翰逊综合征,药物停用。
只要为每个个体提供足够的剂量,每日三次(偶尔更高剂量,四次)服用维拉帕米预防CH非常有效。在大多数(94%)发作性CH患者中,在监测下稳定增加剂量可完全抑制发作。然而,在慢性CH患者中只有55%完全缓解,男性为69%,女性仅为20%。在两组中,对于那些发作部分得到抑制的患者,需要额外的预防性药物或急性治疗。