Tuchman Michael, Hee Angela, Emeribe Ugochi, Silberstein Stephen
Palm Beach Neurological Center, Palm Beach Gardens, FL 33418, USA.
CNS Drugs. 2006;20(12):1019-26. doi: 10.2165/00023210-200620120-00005.
To determine the efficacy and tolerability of zolmitriptan 2.5 mg oral tablet as an acute treatment for menstrual migraine attacks.
This was a two-phase, multicentre, randomised, double-blind, placebo-controlled, parallel-group outpatient study (Phase I is reported here). The study was conducted at 27 sites in the USA. Eligible women were randomised (1 : 1) to receive either zolmitriptan 2.5 mg oral tablet or placebo, and instructed to acutely treat up to two menstrual migraine attacks per menstrual period for up to three menstrual cycles with a single dose of study medication. Menstrual migraine was operationally defined as an attack occurring within the time period of 2 days prior to the expected onset of menses to 5 days after the onset of menses. Participants were asked to treat migraine headaches of moderate or severe intensity only that occurred >24 hours after the end of the last migraine attack and that had not been acutely treated with other medications. Information regarding each migraine attack was recorded by patients in treatment diary cards. The primary efficacy variable was 2-hour headache response (defined as a 2-point drop on a 4-point scale) for all attacks treated. Secondary variables included 1- and 4-hour headache response rate; 1-, 2- and 4-hour headache response based on a 100 mm visual analogue scale (VAS); pain-free rate at 1, 2 and 4 hours; use of escape medication; the proportion of patients with recurrence within 24 hours of initial treatment; and tolerability.
The intention-to-treat population comprised 334 patients (zolmitriptan [n = 174]; placebo [n = 160]). Patients treated 625 attacks with zolmitriptan and 529 attacks with placebo. Twice as many patients who took zolmitriptan achieved a 2-hour headache response compared with placebo recipients (65.7% vs 32.8%; p < 0.0001). Furthermore, a significantly higher headache response was observed with zolmitriptan than placebo at all timepoints assessed. Significantly more zolmitriptan recipients were pain-free 2 hours post-dose compared with placebo recipients (p < 0.0001). The use of escape medication was considerably lower in zolmitriptan recipients (42.6% vs 71.3%; p < 0.0001). Based on the reduction in VAS score of > or = 30 mm from baseline, significantly more zolmitriptan recipients achieved headache response compared with placebo recipients at 1, 2 and 4 hours post-dose (all p < 0.0001). Recurrence was reported in 29.1% of zolmitriptan-treated attacks versus 45.1% of placebo-treated attacks (p = 0.0009), with median time to recurrence of 8.5 and 4.0 hours, respectively. Zolmitriptan was well tolerated.
Oral zolmitriptan is effective and well tolerated for the acute treatment of menstrual migraine attacks. The results are similar to those seen with zolmitriptan in studies of the general migraine population.
确定2.5毫克口服佐米曲普坦片作为月经性偏头痛发作急性治疗药物的疗效和耐受性。
这是一项两阶段、多中心、随机、双盲、安慰剂对照、平行组门诊研究（本文报告第一阶段）。该研究在美国27个地点进行。符合条件的女性被随机分组（1:1），分别接受2.5毫克口服佐米曲普坦片或安慰剂，并被指导在每个月经周期使用单剂量研究药物急性治疗多达两次月经性偏头痛发作，为期最多三个月经周期。月经性偏头痛在操作上被定义为在预期月经开始前2天至月经开始后5天内发生的发作。参与者被要求仅治疗上次偏头痛发作结束24小时后出现的中度或重度偏头痛，且未用其他药物进行急性治疗。患者在治疗日记卡中记录每次偏头痛发作的信息。主要疗效变量是所有接受治疗发作的2小时头痛缓解情况（定义为在4分制量表上下降2分）。次要变量包括1小时和4小时头痛缓解率；基于100毫米视觉模拟量表（VAS）的1小时、2小时和4小时头痛缓解情况；1小时、2小时和4小时无痛率；急救药物的使用；初始治疗后24小时内复发患者的比例；以及耐受性。
意向性治疗人群包括334例患者（佐米曲普坦组[n = 174]；安慰剂组[n = 160]）。患者用佐米曲普坦治疗了625次发作，用安慰剂治疗了529次发作。与接受安慰剂的患者相比，服用佐米曲普坦的患者实现2小时头痛缓解的人数是其两倍（65.7%对32.8%；p < 0.0001）。此外，在所有评估的时间点，佐米曲普坦组的头痛缓解情况均显著高于安慰剂组。与接受安慰剂的患者相比，服用佐米曲普坦的患者在给药后2小时无痛的人数显著更多（p < 0.0001）。服用佐米曲普坦的患者急救药物的使用显著更低（42.6%对71.3%；p < 0.0001）。基于VAS评分从基线降低≥30毫米，与接受安慰剂的患者相比，服用佐米曲普坦的患者在给药后1小时、2小时和4小时实现头痛缓解的人数显著更多（所有p < 0.0001）。佐米曲普坦治疗的发作中有29.1%报告复发，而安慰剂治疗的发作中有45.1%报告复发（p = 0.0009），复发的中位时间分别为8.5小时和4.0小时。佐米曲普坦耐受性良好。
口服佐米曲普坦对月经性偏头痛发作的急性治疗有效且耐受性良好。结果与佐米曲普坦在一般偏头痛人群研究中的结果相似。
