妥泰预防偏头痛发作的临床研究

目的：观察妥泰对偏头痛发作的预防作用。方法：将82例偏头痛患者随机分为妥泰组(42例)，尼莫地平及心得安组(40例)，疗程1月，观察3月。观察上述两组治疗前后头痛指数和1月内头痛总天数的变化。结果：妥泰组头痛指数及1月内头痛总天数皆较尼莫地平及心得安组显著降低。结论：妥泰对偏头痛发作具有更好的预防作用。     

托吡酯联合普萘洛尔预防偏头痛发作的效果

目的：观察托吡酯联合普萘洛尔对预防偏头痛发作的效果。方法：将65例偏头痛患者分为托吡酯联合普萘洛尔组（34例）和普萘洛尔组（31例），疗程8周，观察两组治疗前后头痛发作程度、头痛发作天数等指标的改变。结果：托吡酯联合普萘洛尔组和普萘洛尔组治疗前后头痛发作程度、头痛发作天数指标均有改善．差异均有统计学意义，P〈0．01；同时托吡酯联合普萘洛尔组同普萘洛尔组相比，前者头痛发作程度、头痛发作天数较后者低，差异有显著性，P〈0．01。结论：普萘洛尔、托吡酯联合普萘洛尔对预防偏头痛发作有较好的作用。托吡酯联合普萘洛尔较单独使用普萘洛尔预防偏头痛发作的效果更好。[著者文摘]     

托吡酯预防成人偏头痛发作的临床研究

三项较大规模的随机双盲研究证明,托吡酯可以预防成人偏头痛的发作.与较经典的偏头痛预防性治疗药物相比,托吡酯对成人偏头痛的发作次数、头痛天数、头痛强度及头痛指数的降低不低于经典预防方法,如B受体拮抗剂普萘洛尔、三环类抗抑郁药阿米替林、抗癫痫药丙戊酸等,且较上述治疗方法的副作用小.     

托吡酯治疗偏头痛的近期疗效

目的:观察托吡酯治疗偏头痛的近期疗效。方法:选取偏头痛病人72例,随机分为托吡酯组和对照组,每组36例。比较两组治疗后偏头痛疼痛强度、持续时间及治疗总有效率。结果:两组病人治疗后偏头痛均有改善,疼痛强度减轻,头痛持续时间缩短(P<0.01);与对照组比较,托吡酯组疼痛强度减轻明显,头痛持续时间更短(P<0.05),治疗后1个月止痛显效病例明显增加(χ2=8.02,P<0.01),总有效率显著提高(χ2=7.41,P<0.05)。结论:托吡酯治疗偏头痛,可以缩短病程,改善头痛症状,近期效果满意。     

都梁丸联合托吡酯治疗难治性偏头痛的临床效果及安全性分析

目的观察都梁丸联合托吡酯治疗难治性偏头痛的临床效果及安全性。方法选取延安大学附属医院收治的难治性偏头痛64例,按照治疗方法不同分为观察组与对照组两组各32例。观察组采用都梁丸联合托吡酯治疗,对照组采用托吡酯治疗。观察比较两组治疗后临床效果,治疗前后头痛评估指标和大脑动脉血流速度,以及治疗期间不良反应发生情况。结果治疗后,观察组总有效率90. 63%明显高于对照组总有效率71. 88%,差异有统计学意义(P 0. 05)。治疗前,两组疼痛评估指标及各大脑动脉血流速度比较差异均无统计学意义(P 0. 05)。治疗后,两组头痛发作频率、头痛持续时间、头痛程度评分及大脑前动脉(ACA)、大脑中动脉(MCA)、椎动脉(VA)、基底动脉(BA)、大脑后动脉(PCA)血流速度均明显低于治疗前,且观察组头痛发作频率、头痛持续时间、头痛程度评分及ACA、MCA、VA、BA、PCA血流速度均明显低于对照组,差异有统计学意义(P 0. 05)。治疗期间,观察组不良反应总发生率12. 50%高于对照组不良反应总发生率9. 38%,但两组比较差异无统计学意义(P 0. 05)。结论都梁丸联合托吡酯治疗难治性偏头痛临床效果良好,可以明显降低或缩短头痛发作频率、头痛持续时间及头痛程度,加速脑组织血流恢复,且安全性较好。     

托吡酯治疗儿童偏头痛58例临床疗效观察

目的:观察托吡酯治疗儿童偏头痛的疗效。方法:将58例患儿分为治疗组和对照组。治疗组给予托吡酯每日0.5mg/kg起始,每晚1次或分成2次口服,每周增加0.5～1mg/kg,若在加量期头痛已缓解则停止加量。对照组给予氟桂利嗪2.5～5mg/d,睡前服。用药12周时评定疗效。结果:(1)两组治疗偏头痛后患儿头痛发作的频率均有明显减少和缩短,总有效率分别达到87%和61%,但服用托吡酯治疗头痛显效率及总有效率与对照组相比差异有显著性(P<0.01,P<0.05)。(2)托吡酯治疗儿童偏头痛时用量明显少于治疗癫痫,最小剂量在每日0.5mg/kg即可达到控制发作。(3)服用托吡酯的不良反应发生率低于氟桂利嗪。结论:托吡酯治疗儿童偏头痛有效,值得临床推广。     

托吡酯治疗偏头痛疗效及对神经元放电和脑血流的影响

目的:探讨托吡酯在偏头痛患者中的临床效果及对神经元放电和脑血流的影响。方法:选取2015年5月至2018年1月曹县人民医院收治的偏头痛患者100例,根据治疗方案分为对照组和观察组,每组50例。比较2组治疗前和治疗后2个月头痛发作、持续时间和头痛评分。结果:通过比较2组治疗后头痛发作、持续时间及头痛评分均少(短)于治疗前(P0.05);观察组治疗后2个月头痛发作、持续时间及头痛评分,均少(短)于对照组(P0.05);观察组与对照组脑蛋白变性发生率差异无统计学意义(P0.05);观察组α波频率降低、δ波增多及θ波增多率,均高于对照组(P0.05);观察组治疗后3个月椎动脉、基底动脉、大脑前动脉、中中脉及后动脉血流速度,均高于对照组(P0.05)。结论:将托吡酯用于偏头痛患者中有助于减少偏头痛发作次数,改善神经元放电及脑血流速度,值得推广应用。     

托吡酯预防偏头痛发作的研究进展

偏头痛是一种反复发作的一侧或两侧搏动性头痛.由于头痛程度剧烈,反复发作,常伴有恶心呕吐等植物神经功能症状,发作时常严重影响患者的学习、生活及工作,频繁的发作有可能转化为慢性头痛,因此部分患者常需要预防性治疗.预防偏头痛发作的药物包括钙离子拮抗剂、β受体阻滞剂、抗癫痫药物、α2受体拟似剂、5-HT受体拮抗剂、抗抑郁药物等,但由于均有不同程度的副作用而限制了这些药物的临床应用.近期的一些循证医学证据表明新的抗癫痫药物托吡酯能够有效预防偏头痛发作,本文综述了近年来托吡酯在预防偏头痛发作方面的研究进展.     

氟桂利嗪与托吡酯治疗小儿偏头痛对比观察

摘要 目的：比较氟桂利嗪与托吡酯对小儿偏头痛的预防效果。方法：将43例小儿偏头痛患儿随机分为氟桂利嗪组及托吡酯组，疗程6个月，观察2组有效率和胃肠道症状缓解率。结果：氟桂利嗪和托吡酯用于预防小儿偏头痛的有效率分别为90.4%和81.8%，二者差异无显著意义（χ2 =0.671，P＞0.05）；氟桂利嗪组胃肠道症状缓解率显著高于托吡酯组(χ2 =7.337，P<0.05)；托吡酯组有认知障碍副作用。 结论：氟桂利嗪和托吡酯预防小儿偏头痛的疗效近似。但氟桂利嗪对控制小儿偏头痛伴随的胃肠道症状要比托吡酯好，更适合于小儿长期预防性服用。     

国外医学简讯

托吡酯预防性治疗偏头痛安全有效选择487例门诊病人作为研究对象,年龄12～65岁。均有6个月的偏头痛发作史,每月3～12次,月人均累计发作日数不超过15日。符合国际头痛学会诊断标准。将病人随机分为4组,分别口服安慰剂或每日服50、100或200mg的托吡酯,每周递增25mg,8周内达目标剂     

Effect of Prophylactic Administration of Nimodipine in Patients with Migraine

SYNOPSIS
The prophylactic effect of nimodipine in the treatment of migraine headache was assessed in a prospective, placebo-controlled, double-blind trial. Twenty-six patients were studied during a 3-month experimental period (placebo vs nimodipine) following a 1-month period during which all patients received placebo. Results were tabulated using a "headache index". A trend in favour of a beneficial nimodipine effect on the headache index was demonstrated which achieved statistical significance during one month of the follow-up period. A similar trend with respect to the overall number of headaches was demonstrated and achieved statistical significance during two months of the follow-up period. We conclude that nimodipine is a potentially useful agent in the prophylaxis of migraine headache.     

Prophylaxis of Migraine and Mixed Headache. A Randomized Controlled Study

SYNOPSIS
The three most commonly used modalities in the prophylactic treatment of headache, namely propranolol, amitriptyline and biofeedback training, were compared individually and in combination. Three hundred forty patients with migraine end 375 patients with mixed headache were randomly allotted to 8 therapeutic categories. The total duration of the study was 312 years and the therapeutic groups were evaluated for a period of 7 months including I month of pretreatment observation. Improvement was assessed by percentage of change in the average headache index during the last three months of evaluation from the pretreatment headache index. In the migraine group 273 patients completed the study. Improvement was significantly higher in patients receiving prophylactic treatment compared to control patients who were on abortive Ergotamine treatment. Propranolol plus biofeedback yielded the best results in the migraine group and addition of amitriptyline did not significantly change the percentage of improvement. Propranolol alone (62%) was significantly superior to amitriptyline (42%) (p < 0.01). The differences between propranolol alone and propranolol plus amitriptyline was not statistically significant.
In the mixed headache group 281 patients completed the study. The most effective treatment was combination of amitriptyline, propranolol and biofeedback training. Amitriptyline alone was superior to propranolol alone in the treatment of mixed headache (p<0.01). A combination of propranolol and amitriptyline was superior to either of those alone. Biofeedback, though by itself, did not appear to be the treatment of choice, significantly contributed to better results as an adjunct when it is combined with pharmacological agents. Concomitant use of propranolol and amitriptyline did not result in any adverse reactions or clinical incompatibility.     

Medication overuse headache: a critical review of end points in recent follow-up studies

No guidelines for performing and presenting the results of studies on patients with medication overuse headache (MOH) exist. The aim of this study was to review long-term outcome measures in follow-up studies published in 2006 or later. We included MOH studies with >6 months duration presenting a minimum of one predefined end point. In total, nine studies were identified. The 1,589 MOH patients (22% men) had an overall mean frequency of 25.3 headache days/month at baseline. Headache days/month at the end of follow-up was reported in six studies (mean 13.8 days/month). The decrease was more pronounced for studies including patients with migraine only (−14.6 days/month) compared to studies with the original diagnoses of migraine and tension-type headache (−9.2 days/month). Six studies reported relapse rate (mean of 26%) and/or responder rate (mean of 28%). Medication days/month and change in headache index at the end of follow-up were reported in only one and two of nine studies, respectively. The present review demonstrated a lack of uniform end points used in recently published follow-up studies. Guidelines for presenting follow-up data on MOH are needed and we propose end points such as headache days/month, medication days/month, relapse rate and responder rate defined as ≥50% reduction of headache frequency and/or headache index from baseline.     

Topiramate vs divalproex sodium in the preventive treatment of migraine: a prospective "real-world" study

(Headache 2011;51:554‐558) Background and objectives.— Certain neuromodulators, most notably topiramate (TPM) and divalproex sodium (DVP), are effective preventive agents for migraine. Published data from head‐to‐head studies comparing TPM and DVP are not available. The purpose of this study was to compare TPM and DVP for the prophyaxis of migraine in a “real‐world” setting. Methods.— At 2 centers and over a period of 12 months we prospectively evaluated and treated a consecutive series of migraine patients. At baseline all were experiencing less than 15 headache days/month, and we treated all patients requiring prophylactic therapy with either TPM or DVP. We evaluated adherence, headache frequency (HF) and tolerability after 3 months of treatment. TPM treatment was initiated at 25 mg daily and increased every 10 days (25 mg) to a target of 150 mg/day (2 divided doses/day). Treatment with DVP was initiated at 250 mg daily and sequentially titrated up to 500 mg twice daily. All patients were naïve to the use of TPM and DVP. Results.— One hundred and twenty patients (104 women and 16 men of ages 18 to 68, mean 41.2 years) were included. Topiramate selectively was prescribed to 69 patients and DVP selectively to 51. Baseline HF for both groups was similar (8 ± 4 headache days/month). By intention to treat analysis at 3 months, 40 (58%) of patients initially treated with TPM and 26 (51%) of those initially treated with DVP experienced a reduction in HF of >50% (P = NS). Ten patients (14.5%) initially treated with TPM and 8 (15.7%) initially treated with DVP did not return for follow up or were begun on alternative prophylactic therapy. The most common side effects manifested by TPM patients were weight loss (50% of those who completed the treatment period), paresthesia (48%), and cognitive disturbances (20%), whereas DVP patients who completed the treatment period reported weight gain, hair loss, and gastrointestinal symptoms (approximately 24% for each). The mean doses achieved by those completing the study were 140 mg/day for TPM and 890 mg/day for DVP. Conclusions.— Although any conclusions from this investigation necessarily are limited because of our study's open‐label nonrandomized design, these results suggest that TPM and DVP are reasonably effective and generally well tolerated when used to treat a “real‐world” population of episodic migraineurs who require prophylaxis.     

Treatment of patients with chronic headaches in a hospital for traditional Chinese medicine in Germany. A randomised, waiting list controlled trial

OBJECTIVE: To investigate the effectiveness of a clinical treatment program with traditional Chinese medicine for migraine and tension-type headache. METHODS: Ninety-one patients with migraine, episodic or chronic tension-type headache according to the criteria of the International Headache Society were randomised into an experimental or a waiting list control group. Patients in the experimental group were treated 4 weeks in a hospital for traditional Chinese medicine after a baseline period of one month. Patients in the waiting list group continued their previous headache treatment. Main outcome measure was the difference in the number of days with headache of at least moderate intensity during baseline (month 1) and month 7. RESULTS: The difference in the number of days with headache of at least moderate intensity was 5.6 (S.D., 6.1) days in the experimental group and 1.2 (S.D., 4.5) days in the waiting list group (P <0.001). A reduction of more than 50% in headache days was observed in 52% of the patients in the experimental group and 16% in the waiting list group. Patients with migraine and a combination of migraine and episodic tension-type headaches improved more than patients with other headaches. CONCLUSION: The results of this study indicate that treatment in the hospital for traditional Chinese medicine in Kotzting is associated with lasting improvements in the majority of patients.     

偏头痛与卵圆孔未闭关系的研究

目的：探讨先兆性偏头痛、无先兆性偏头痛患者和正常人卵圆孔未闭（ PFO）发生率的差异。方法采用经颅多普勒超声（TCD）检测先兆性偏头痛组（29例）、无先兆偏头痛组（31例）和正常对照组（26名） PFO的发生率,比较各组差异。记录治疗前偏头痛患者的头痛频率、头痛发作日数和头痛程度等,并分析其与PFD分流量大小的相关性。结果先兆性偏头痛组、无先兆偏头痛组和正常对照组PFO发生率分别为72％、45％和31％,先兆偏头痛组PFO发生率较正常对照组高（ P＝0.008）,无先兆偏头痛组较正常对照组高,但比较差异尚无统计学意义（ P＝0.491）;PFO大小与头痛频率、头痛发作日数呈正相关（P均＜0.05）。结论先兆偏头痛患者的PFO发生率较高,提示此两种疾病可能有共同的病理学发病机制。     

Expanding Access to Triptans: Assessment of Clinical Outcome

Objective.— To evaluate whether access to more liberal quantities of rizatriptan improves clinical outcome in patients with episodic migraine.
Background.— Currently many pharmacy benefit programs limit the number of triptan tablets/injections per month based on perceived cost savings and the belief that too-frequent use of triptans may lead to medication overuse headache and headache chronification.
Methods.— This observer-blind, randomized, parallel-group study enrolled 197 subjects with migraine with or without aura. Subjects completed a 3-month baseline period to establish migraine frequency and then were randomly assigned to receive 9 (formulary limit [FL]) or 27 (clinical limit [CL]) tablets of 10 mg rizatriptan orally disintegrating tablet (ODT) per month for 3 months. The primary endpoint was change in the mean number of migraine days from the baseline to treatment period.
Results.— There was no statistically significant difference between the FL and CL groups in mean number of migraine days (FL-CL LS mean: −0.08 [−0.39, 0.23]; P  = .613). Subjects in the CL group treated attacks at lower headache severity. No CL subjects were reported to have developed chronic migraine despite utilization of greater than 10 rizatriptan ODT tablets per month. Rizatriptan was generally well tolerated by both groups.
Conclusion.— Providing a greater quantity of rizatriptan ODT 10 mg did not reduce the number of migraine days compared with providing 9 tablets per month for this population with episodic migraine with a frequency of 3-8 migraines per month. Regardless of quantity provided, rizatriptan was generally well tolerated.     

Prevalence of migraine and non-migrainous headache--head-HUNT, a large population-based study

The objective of this study was to estimate the 1-year prevalence of the following categories of headache; migraine, non-migrainous headache, frequent headache (>6 days/month), and chronic headache (>14 days/month). Between 1995 and 1997, all 92,566 inhabitants 20 years and older in Nord-Tr?ndelag county in Norway were invited to a comprehensive health study. Out of 64,560 participants, a total of 51,383 subjects (80%) completed a headache questionnaire. The overall age-adjusted 1-year prevalence of headache was 38% (46% in women and 30% in men). The prevalence of migraine was 12% (16% in women and 8% in men), and for non-migrainous headache 26% (30% in women and 22% in men). For frequent headache (> 6 days per month) and for chronic headache (>14 days per month), the prevalence was 8% and 2%, respectively. Women had a higher prevalence than men in all age groups and for all headache categories. Prevalence peaked in the fourth decade of life for both men and women, except for 'frequent non-migrainous headache', which was nearly constant across all age groups in both genders. In accordance with findings in other western countries, we found that headache suffering, including migraine, was highly prevalent, especially in younger women.     

Topiramate as an adjunctive treatment in migraine prophylaxis

BACKGROUND: Anticonvulsants now are commonly used for headache prevention. Topiramate, one of the newer anticonvulsants, recently has been demonstrated to be effective as monotherapy for migraine prophylaxis. OBJECTIVE: To assess the efficacy, safety, and tolerability of topiramate as adjunctive prophylactic therapy for migraine. MATERIAL AND METHODS: A prospective trial involving patients with more than 3 migraine attacks per month was performed. Patients continued their usual prophylactic treatment. Baseline analgesic use and frequency and duration of migraine attacks were recorded. A 4-point visual analog scale evaluated severity. Laboratory tests, electrocardiogram, and computed tomography or magnetic resonance imaging were performed before study entry. After informed consent was obtained, patients were instructed to take 25 mg of topiramate per day, with 25- to 50-mg weekly increments to a maximum of 100 mg per day. Safety was assessed at the first month; tolerability and efficacy were assessed every week for the first month and then every month for 3 months. Effectiveness was assessed by comparing baseline and on-treatment migraine status, and data were analyzed by the Fisher exact test. RESULTS: Twenty-five women and 11 men (mean age, 44 years) were evaluated. Existing prophylactic treatment was either propranolol or flunarizine (or both) in 80% of the patients. At 3 months of therapy with topiramate, headache frequency decreased from 17 to 3 episodes per month, headache duration from 559 to 32 minutes, and intensity from 9 to 1 by visual analog scale (P <.001). Improvement in frequency and severity of migraine was observed in 83% of patients. Slight or no changes in headache were observed in 6 patients. Tolerability was good in 30 patients. The most common side effects were acroparesthesias, weight loss, sleepiness, and headache worsening. No adverse interaction with propranolol or flunarizine was observed. CONCLUSIONS: These results suggest that topiramate is efficacious and safe as an adjunctive treatment in patients with migraine whose prior response to prophylactic management has been less than satisfactory.     

The effect of propranolol on glyceryltrinitrate-induced headache and arterial response

Prophylactic drug trials in migraine are long-lasting and expensive and require long-term toxicology information. A human migraine model would therefore be helpful in testing new drugs. Immediate headache and delayed migraine after glyceryltrinitrate (GTN) has been well characterized. We have recently shown that sodium valproate has prophylactic effect in the GTN model. Here we report our experience with propranolol in this model. Nineteen subjects with migraine without aura and 16 sex- and aged-matched healthy subjects were included in a two-centre randomized double-blind cross-over study. Fourteen migraine subjects and 14 healthy subjects completed the study and results from comparison of the 28 subjects are reported. Randomly propranolol 160 mg or placebo were each given daily for 14 days to both migraine and healthy subjects. A 20-min intravenous infusion of GTN 0.25 microg/kg per min was administered on a study day at the end of both pretreatment periods. Headache was registered for 12 h after GTN infusions. Its intensity was scored on a numerical verbal rating scale from 0 to 10. Fulfilment of International Headache Society (HIS) criteria was recorded for 24 h. Radial and superficial temporal artery diameters and blood velocity of both middle cerebral arteries were measured. All migraine subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 5, range 0-7) compared with placebo (median 5, range 0-10) (P = 0.441). Eight of the 14 completing migraine subject developed IHS 1.1 migraine after GTN, two subjects on both days, three subjects only after placebo, and three subjects only after propranolol. No reduction of GTN-induced migraine was found after propranolol compared with placebo (5 vs. 5, P = 1.000). All healthy subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 2, range 1-5) compared with placebo (median 1, range 1-7) (P = 0.315). Two subjects fulfilled IHS criteria 1.1 for migraine without aura after propranolol but not after placebo. The fulfilment was short lasting and did not require rescue medication. Headache after GTN was more pronounced in migraine subjects than in healthy subjects both with (P = 0.003) and without pretreatment with propranolol (P = 0.017). We found that 2 weeks of propranolol constricted the radial artery in healthy subjects but not in migraine subjects. GTN-induced vasodilatation abolished this difference. Mean maximum blood flow velocity in the middle cerebral artery was higher in healthy subjects than in migraine patients (P = 0.003-0.033) and unaffected by propranolol. We observed no effect of propranolol on GTN-induced headache and migraine. This could indicate that GTN induces migraine at a deeper level of the pathophysiological cascade of migraine than the prophylactic effect of propranolol. Propranolol does not constrict cerebral arteries, which therefore cannot be part of its mechanism of action in migraine.