A型肉毒毒素不适用于预防头痛

《美国医学会杂志》4月25日发表的一项Meta分析显示，尽管注射A型肉毒毒素可在一定程度上预防慢性偏头痛和慢性日常头痛，但不能有效预防发作性偏头痛、发作性紧张型头痛或慢性紧张型头痛(JAMA 2012;307:1736-45)。

Zablocki退伍军人事务部医疗中心的Jeffrey L. Jackson博士及其同事通过检索文献，查找到31项为期至少4周的比较A型肉毒毒素注射与安慰剂注射或预防性药物的临床随机对照研究。在27项涉及成人的安慰剂对照研究中，受试者的平均年龄为42岁，平均研究时间为19周(84~270天)。共1,938例受试者患发作性偏头痛，1,544例患慢性偏头痛，616例患慢性紧张型头痛，1,115例患日常头痛。

分析结果显示，注射A型肉毒毒素可使慢性偏头痛次数从19.5次/月降至17.2次/月，以及使慢性日常头痛次数从17.5次/月降至15.4次/月(不清楚降幅是否具有临床意义)，但不能降低其他类型头痛的频率。此外，在对照受试者中观察到明显的安慰剂效应，有明显数量的对照受试者报告称头痛随时间推移而减少。

研究者还分析了4项比较A型肉毒毒素注射与预防性药物的研究，结果发现，前者预防任何类型头痛的效果并不优于托吡酯、阿米替林或丙戊酸。

一项比较A型肉毒毒素与甲基强的松龙的研究显示，注射A型肉毒毒素不能降低头痛严重程度，但由于糖皮质激素通常不用于预防头痛，因此尚不清楚此类比较的临床意义有多大。

与注射安慰剂的受试者相比，注射A型肉毒毒素的受试者更常发生以下不良反应，包括上睑下垂、肌无力、颈部疼痛、颈部僵硬、感觉异常和皮肤紧缩。

不管是根据固定方案还是根据灵活方案给药，不管注射了哪些特定肌肉群，也不管是否根据患者的疼痛主诉选择注射部位，注射A型肉毒毒素的预后均相同。不管是只注射1次还是间隔90 d注射3次，预后也均相同。另外，不管注射多少个肌肉群或所注射的A型肉毒毒素总剂量如何，预后也相同。

该分析的局限性在于探讨各种头痛亚型的研究相对较少并且这些研究的规模也较小。

研究者声明无相关经济利益冲突。

爱思唯尔  版权所有

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

Injections of botulinum toxin A may be of some benefit in preventing chronic migraine and chronic daily headaches, but that benefit is small and does not extend to episodic migraine, episodic tension-type headaches, or chronic tension-type headaches, according to a report in the April 25 issue of JAMA.

In a metaanalysis of 31 randomized controlled trials, botulinum toxin A injections reduced the number of chronic migraine headaches from 19.5 to 17.2 per month and the number of chronic daily headaches from 17.5 to 15.4 per month, differences of unknown clinical importance. The treatment did not reduce the frequency of other types of headache, said Dr. Jeffrey L. Jackson of the Zablocki Veterans Affairs Medical Center and the Medical College of Wisconsin, Milwaukee, and his associates.

“Our finding of minimal benefit is contrary to findings from case series and open-label studies that suggested substantial benefits. These differences in results may be due to a strong association of placebo with improved outcomes and the natural history of headaches, in which improvement is observed over time,” they noted.

Dr. Jackson and his colleagues searched the literature for randomized clinical trials of at least 4 weeks’ duration that compared botulinum toxin A injections against either placebo injections or prophylactic medications.

In 27 placebo-controlled trials involving adults, the average subject age was 42 years and the average duration of the study was 19 weeks (range, 84-270 days). A total of 1,938 of these subjects had episodic migraines, 1,544 had chronic migraines, 616 had chronic tension-type headaches, and 1,115 had chronic daily headaches.

Botulinum toxin A injections were associated with a reduction of approximately two headaches per month for both chronic migraine and chronic daily headaches, but did not reduce the other types of headache. Moreover, there was a “substantial” placebo effect among control subjects, with a significant number of them reporting reduced headaches over time.

The researchers also analyzed four trials that compared the injections against prophylactic medications. Botulinum toxin A injections were no more effective than were topiramate, amitriptyline, or valproate at preventing any type of headache.

The injections did reduce headache severity in a single trial comparing them against methylprednisolone, but given that corticosteroids are not generally used for headache prophylaxis, “it is unclear how useful this comparison is clinically,” Dr. Jackson and his associates said (JAMA 2012;307:1736-45).

Study subjects who received botulinum toxin A injections were more likely to report adverse effects than were those who received placebo injections, including blepharoptosis, muscle weakness, neck pain, neck stiffness, paresthesia, and skin tightness.

Outcomes with botulinum toxin A injections were the same regardless of whether they were administered on a fixed or a flexible schedule, whether particular muscle groups were injected, or whether injection sites were selected on the basis of patients’ pain reports. Outcomes also were the same whether the injections were performed once, or three times at 90-day intervals.

There also were no differences in outcomes according to the number of muscle groups injected or the total dose of botulinum toxin A administered, the investigators added.

Among the study’s limitations was the fact that for nearly all the headache subtypes, there were relatively few studies and may of the studies were small.

No relevant financial conflicts of interest were reported.