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一项新研究结果显示，zolmitriptan（ZNS）（Zomig，阿斯特捷利康药厂制造）提供丛聚性头痛（CH）快速、有效的治疗，这是一种严重原发性头痛。
这项双盲、多中心、随机分派的交替临床研究发现，相较于50%使用5 mg以及30%使用安慰剂的受试者，63%接受10 mg ZNS治疗的受试者，在30分钟内缓解头痛。
主要研究者康乃狄克州史坦佛新英格兰头痛中心Alan M. Rapoport医师在美国神经医学会上的一项声明中指出，这项研究的发现与研究中主要终点是很重要的，10 mg的剂量在10分钟内对某些病患就会有效。
Rapoport医师附带表示，丛聚性头痛是一种没有药物可以治疗的状况，没有什么使用于丛聚性头痛的药物被系统性地测试，只有一种，以静脉注射sumatriptan已经获得美国食品药物管理局（FDA）核准用于治疗丛聚性头痛。
这项研究发表于8月28日的神经学期刊。
总共有52位来自美国4个头痛中心罹患阵发性或慢性CH的成人病患被收纳到这项研究中，试验的主要终点为头痛反应，以中、重度或是非常严重的头痛，在30分钟内缓解到轻度、或是没有疼痛定义。
次级试验终点包括用药30分钟后头痛缓解病患的比例、在其他研究时间点时达到头痛缓解、以及使用紧急缓解药物。
不良反应以可能与药物有关的任何不舒适症状、或是新的病征或症状来定义，且与使用安慰剂受试者比较。
【少见的情况】
这是一种少见的情况，仅有0.07%~0.4%的美国人口发生丛聚性头痛，且男性发生的比例比女性高出3~4倍；根据作者表示，该研究的3次发作交替设计增加研究这个少见情况的统计力量；除此之外，他们附带表示，一个ZNS可能的影响残余效应是这个药物的半衰期太短。
受试者被随机分派接受以下的治疗顺序，分别是安慰剂、ZNS 5 mg、或是ZNS 10 mg，每个次序以同样的机率平衡分派情形，每位受试者的3次发作之间都至少间隔24小时以上。
所有的受试者都被教导将他们的头痛程度以5分分级，其中1分代表没有头痛、而5分代表非常严重的头痛；同时也以问卷评估使用紧急缓解药物、任何头痛缓解、以及不良反应的发生。
在评估头痛程度后，受试者使用在两个鼻孔都使用一试验用喷雾，接着自使用后5、10、15、20、30与60分钟评估头痛程度；这项研究中，总共治疗了151次丛聚性头痛发作。
研究者发现，以5 mg、10 mg的ZNS在CH的急性治疗中是有效的；作者指出，这两个剂量在30分钟内提供头痛缓解，这项研究的主要试验终点，都显著地比安慰剂好；10 mg剂量的15分钟内免于头痛的比例也显著较高，然而，5 mg剂量在20分钟内显著地比安慰剂好。
【FDA并未核准】
三组之间使用紧急缓解药物的比例相近，安慰剂组中有38%、5 mg与10 mg剂量ZNS组分别有30%与28%；除此之外，接受安慰剂治疗的不良反应较为轻微，且仅有16%，相较于接受5 mg ZNS治疗组的25%、10 mg ZNS治疗组的32.7%；在研究中并未发生严重不良反应。
根据作者表示，这些研究结果显示，该药物可能有效地以非静脉注射投予治疗丛聚性头痛，且与最近一项于欧洲进行的临床研究结果相似。
他们指出，ZNS是有效的，且至少在短期的临床研究中显示该药物于治疗CH的耐受性良好，且应该被考虑作为适当病患急性处理该症状的第一线治疗。
然而，他们警告，FDA尚未核准zolmitriptan 10 mg以单一剂量使用于任何适应症。
该研究由阿斯特捷利康药厂赞助。
Zolmitriptan Nasal Spray May Fill Treatment Void for Cluster Headache
By Caroline Cassels
Medscape Medical News
New research suggests zolmitriptan nasal spray (ZNS) (Zomig, AstraZeneca) provides rapid, effective treatment for cluster headaches (CH), 1 of the most severe primary headache types.
The double-blind, multicenter, randomized crossover trial found 63% of subjects treated with 10-mg ZNS achieved headache relief within 30 minutes, compared with 50% of those taking 5 mg of the drug and 30% of those in the placebo group.
"This is a significant finding and the main end point of our study. The 10-mg dose worked in as quickly as 10 minutes in some patients," principal investigator Alan M. Rapoport, MD, from the New England Center for Headache, in Stamford, Connecticut, said in a statement from the American Academy of Neurology.
Dr. Rapoport added that cluster headache is a condition with enormous unmet treatment needs. "Few medications for cluster headache have been systematically tested, and only 1, which involves an injection of sumatriptan, has been [Food and Drug Administration] FDA approved," he said.
The study is published in the August 28 issue of Neurology.
A total of 52 adult patients with episodic or chronic CH from 4 headache centers in the United States were included in the study. The primary end point was headache response — pain reduced from moderate, severe, or very severe at baseline to mild or none at 30 minutes.
Secondary outcome measures included percentage of patients with no pain at 30 minutes, headache relief and freedom from pain at other study time points, and use of rescue medication.
Adverse events were defined as any unpleasant symptom or new sign or symptom that could be attributed to the drug and were assessed in comparison with those seen with placebo.
Uncommon Condition
A relatively rare condition, cluster headache occurs in 0.07% to 0.4% of the US population and is 3 to 4 times more common in men than women. According to the authors, the study's 3-attack crossover design increased the power of studying this uncommon condition. Furthermore, they note, a possible confounding residual effect of ZNS was limited by the medication's short half-life.
Subjects were randomly assigned to a treatment sequence of placebo, ZNS 5 mg, or ZNS 10 mg in balanced blocks with equal probability for each sequence. Each subject's 3 treated attacks had to be separated by a minimum of 24 hours.
All subjects were instructed to grade their pain on a 5-point scale, with 1 indicating no pain and 5 very severe pain. The questionnaire also assessed use of rescue medication, any headache relief, and adverse events.
Immediately after assessing pain intensity, subjects applied 1 study spray in each nostril. Subsequent pain assessments occurred at postdose time points of 5, 10, 15, 20, 30, and 60 minutes. A total of 151 cluster headache attacks were treated in the study.
The investigators found that ZNS at doses of 5 mg and 10 mg is effective in the acute treatment of CH. "Both doses were significantly better than placebo in providing headache relief at 30 minutes, the primary end point of our study. The 15-minute pain-free rates were also significantly higher for 10 mg, whereas ZNS 5 mg was significantly superior to placebo at 20 minutes," the authors write.
Not FDA Approved
Use of rescue medication was similar between the 3 groups — 38% in the placebo group and 30% and 28% in the 5-mg and 10-mg ZNS groups, respectively. Furthermore, adverse effects were mild and seen in 16% of attacks treated with placebo, 25% of those treated ZNS 5 mg, and 32.7% treated with ZNS 10 mg. No serious adverse events were reported during the study.
According to the authors, these results demonstrate that it is possible to effectively treat cluster headaches with a drug that is not delivered parenterally and parallel the findings of a recent, similar European trial of the drug.
"ZNS is effective and, at least in the context of a short-term clinical trial, well tolerated in the treatment of CH and could be considered as first-line therapy in appropriate patients for the acute treatment of this disease," they write.
However, they warn, the FDA has not approved zolmitriptan 10 mg as a single dose for any indication.
The study was supported by AstraZeneca.
Neurology. 2007;69:821-826.