A Double-blind Placebo-controlled Prophylactic Study of Flunarizine (Sibelium®) in Migraine

SYNOPSIS
The potential prophylactic value of a daily dose of 10 mg flunarizine, a calcium antagonist with anti-vasospastic properties was studied in a 3-month double-blind placebo-controlled trial in 58 migraineurs. With an almost perfect mutual correlation, both the patients' overall appreciation of the treatment and the reduction of migraine attacks proved flunarizine to be effective (p<0.001). Half of the flunarizine-patients considered the treatment certainly beneficial in contrast to none of the placebo-patients. In 21 of the 29 flunarizine-patients the attack rate was lower than expected in 20 of the 29 controls it was not. Younger patients appeared to respond better to the treatment. Flunarizine displayed a gradually increasing effect; during the third month 83% of the treated patients were completely attack-free. The drug did not appear to influence the severity and duration of attacks, however. Treatment was very well tolerated. Flunarizine, therefore, appears to be a very suitable agent for migraine prophylaxis but it should be given for more than two months in order to obtain full effectiveness with this dosage.     

Sublingual Flunarizine: a New Effective Management of the Migraine Attack. A Comparison versus Ergotamine

SYNOPSIS
Flunarizine was found to be effective in the acute treatment of isosorbide dinitrate induced migraine attacks, when given in a dosage of 10 mg sublingually.
The present study consists of two parts: in the first preliminary investigation, 7 out of 8 migraine patients who developed a typical migraine attack after isosorbide dinitrate were relieved of pain within about 10 minutes. On the basis of this result a second, randomized controlled open trial was performed, in which the acute efficacy of flunarizine was compared with ergotamine tartrate, 0.25 mg i.m., on 40 migraine patients. Flunarizine was found as effective as ergotamine (75% positive responses in the flunarizine group, 70% in the ergotamine group). The mean latency of the flunarizine effect was significantly lower than that of the ergotamine ( r < 0.001, Student's t test). Moreover sublingual flunarizine was found to be virtually devoid of side effects.     

Migraine and Intercalated Seizures With Occipital EEG Paroxysms: Observations on a Family

SYNOPSIS
A 12-year-old girl presented three distinct attacks of classic migraine. In all attacks, an occipital seizure with impairment of consciousness was intercalated between the visual prodrome and the headache. A right occipital epileptogenic focus was detected by the EEG. Neurologic examination was normal. CT-scan and laboratory work were unremarkable. Flunarizine treatment controlled both the migraine and seizure components. Periodic migraine episodes with visual phenomena occurred in three other female components of the same family. However, the attacks were never associated with epileptic manifestations. Only the 10-year-old sister, who suffered from common migraine, showed sporadic interictal EEG abnormalities in the right posterior leads.
The possible neurophysiologic interplay between classic migraine and epilepsy in intercalated attacks may be explained on the basis of the "spreading depression" mechanism. The intense neuronal excitation preceding the migraine aura might play a "triggering" role on the occipital epileptogenic focus.
Similarities and differences between this benign though unusual syndrome and other forms of epilepsy in childhood, are also discussed.     

Flunarizine I.V. in the Acute Treatment of Common or Classical Migraine Attacks A Placebo-Controlled Double Blind Trial

The efficacy and tolerance of 20 mg flunarizine i.v. were tested in comparison with placebo in a multicentre randomised double-blind trial in the acute treatment of migraine attacks. Sixty case reports were included in the evaluation; 31 patients were treated with flunarizine and 29 with placebo. Flunarizine proved to be significantly superior in its effect on the intensity of pain and the typical concomitant symptoms of the attacks. Patients were classed as responders who displayed a reduction in pain intensity by at least 50% within 60 minutes after the administration of flunarizine. 23 patients (= 74.2%) were responders, including 11 patients being without pain after 60 minutes. In the placebo group the responder rate was 27.6% The fact that both groups were comparable in all respects should be emphasized. The tolerance of intravenously administered flunarizine was excellent and corresponded to that of placebo. Apart from a sedative effect reported by 9 patients there were no side-effects. The circulatory conditions remained largely stable. The result of this study seems to indicate that an intravenous injection of 20 mg flunarizine might represent a genuine alternative, and as regards tolerance even a superior one, to the parenteral administration of ergotamine in migraine attacks.     

Classic Migraine and Intercalated Seizures in a Young Woman: Efficacy of Flunarizine

SYNOPSIS
A case of a young woman suffering from both migraine and epilepsy is reported. Since the age of 28, she complained of classic migraine attacks and of generalized or partial seizures. The seizures often intercalated themselves between the visual prodrome and the painful phase of her attacks. She came to our observation at the age of 31. Neurological examination, laboratory work and CT-scan were normal. The EEG showed an asymmetry of the background activity between the two hemispheres and medium-voltage sharp waves, not blocking upon eye opening, in the left parieto-temporel leads. Flunarizine was added to her anti-convulsant therapy. It remarkably reduced the migraine attacks and controlled the intercalated seizures. After one year, flunarizine was discontinued and two intercalated seizures occurred four months later. The efficacy of flunarizine and its hypothetical mechanism of action in such a clinical condition is discussed.     

Flunarizine in the prevention of classical migraine: a placebo-controlled evaluation

Pharmacological data and early clinical experience have suggested that the calcium entry blocker flunarizine may be a valuable gain in the prophylaxis of migraine. This was supported by a study in 20 patients with classical migraine who were, after a drug free run-in phase, orally treated with either placebo or flunarizine (10 mg at night) for 3 to 4 months. Flunarizine significantly reduced the frequency, duration and severity of the migraine attacks. A corrected migraine index, based on these 3 variables was reduced by 82% in the drug group but increased by 66% in the control patients. Only 1 patient did not clearly benefit from flunarizine. In some cases flunarizine should be administered for at least 4 months before judging its efficacy. No side-effects occurred.     

Propranolol in the treatment of acute migraine attacks

The efficacy of the beta-adrenoceptor antagonist propranolol in the acute treatment of patients in attacks of either classical (migraine with aura) or common migraine (migraine without aura) headache was assessed in a double-blind placebo-controlled crossover trial with fixed doses. The trial was carried out on 25 patients. The treatment period was set at eight weeks, with the provision of shortening or lengthening it if necessary with a maximum period of seventeen weeks. A minimum of three migraine attacks were treated during each treatment period. Patients were assessed according to: the mean duration and mean severity per treatment period of migraine attacks. The secondary efficacy assessment was made on the basis of the percentage of attacks requiring escape medication per treatment period. The study, based on the t-distribution statistical model with a confidence level of 95%, showed that propranolol had no significant effect in aborting acute attacks of migraine when compared with placebo.     

Medikamentöse Migräneprophylaxe

If migraine attacks occur more frequently than 2 times a month, treatment of the acute attack with analgesics and ergotamine becomes problematic. An acute relief of migraine symptoms will be achieved only at the risk of developing a drug-induced chronic headache. Therefore, if migraine attacks occur frequently prophylactic treatment should be considered. A bewildering variety of drugs have been discussed for migraine prophylaxis in the past few decades. Only a few of them can be accepted to be effective on the basis of reliable clinical studies. Others have failed to show any superiority to placebo treatment when tested in controlled drug trials for a period long enough to rule out the placebo response, which may simulate effectiveness at the beginning of the trial. The efficacy of metoprolol and propranolol has been demonstrated beyond any doubt. It seems, however, that other beta-blocking drugs are less effective or even ineffective. In more than 20% of patients even prolonged treatment with metoprolol or propranolol does not provide sufficient relief. Flunarizine may be tried in these patients, as long as side effects do not occur or can be tolerated by the patient. Whether non-steroidal antirheumatics and dihydroergotamine can be considered as an effective and safe alternative in migraine prophylaxis is still not well established. There is, however, convincing evidence that neither clonidine, nor anti-histamines, nor barbiturates, nor antiepileptic drugs, nor anxiolytics are effective in the prophylactic treatment of migraine. Successful prophylactic treatment cannot be achieved by drug therapy alone. Any form of drug treatment should be complemented by providing the patient with detailed information about the nature of the disease and the properties of the prescribed drugs, as well as careful investigation of the patient's situation and habits and a careful search for precipitants, combined with an attempt to change the patient's habits and to avoid factors that trigger the attacks.     

Treatment of Acute Migraine Attack: Ibuprofen and Placebo Compared

The efficacy of ibuprofen in comparison with that of placebo was assessed in the treatment of acute migraine attacks. The material consisted of 40 migraine patients. Each treatment period continued for five migraine attacks. The initial dose of ibuprofen was 800 mg, with additional 400 mg taken if and when needed. The mean duration of migraine attacks treated with ibuprofen was significantly shorter than the duration of migraine attacks treated with placebo. Need for supplementary medication was also significantly lower in the ibuprofen-treated migraine attack group. Ibuprofen was well tolerated and no marked side effects were reported during the trial.     

A double-blind study of ibuprofen versus placebo in the treatment of acute migraine attacks

The efficacy of ibuprofen, a non-steroidal anti-inflammatory drug, was assessed in the acute treatment of migraine. Twenty-five patients completed a double-blind placebo-controlled multicrossover trial. The initial dose of ibuprofen was 1200 mg. Six migraine attacks were randomly treated in each patient, three with ibuprofen and three with placebo. The results indicated a statistically significant reduction in the duration of the migraine attacks and also a statistically significant reduction in the severity of headache and nausea in the ibuprofen-treated attacks. The use of additional medication was significantly reduced in the ibuprofen-treated attacks (25.6% vs 57.5%). No serious side effects were reported. Ibuprofen is valuable in the treatment of acute migraine attacks.     

Flunarizine and migraine in childhood

Flunarizine was tested for prophylactic efficacy and for side effects in 10- to 13-year-old patients with severe migraine (greater than 2 attacks per month). The 13 preadolescents received a single 5-mg dose at night for 2 months. The attack frequency decreased significantly, and the effect was maintained over time. The endocrine status, investigated before and after treatment, showed no significant interference with pituitary, beta-pancreatic, or gonadal function.     

Classic migraine: Effective prophylaxis with metoprolol

Metoprolol slow-release tablets (Durules®), 200 mg, given once daily in the morning were compared with placebo in the prophylaxis of classic migraine. The trial comprised eight Scandinavian neurologic centres and was designed as a double-blind cross-over study with 4 weeks' run-in, four weeks washout, and 8 weeks of either treatment. Seventy-seven patients with two to eight migraine attacks per month were entered in the trial, and 73 completed it. A total of 1119 attacks with aura symptoms and 374 without were recorded. Metoprolol was significantly better than placebo with regard to the total frequency of attacks (1.8 versus 2.5 attacks/4 weeks), mean duration of attacks (6.0 versus 8.0 h/attack), mean global rating, and consumption of analgesics per attack: Similar differences could be shown for attacks with aura symptoms alone, except for the duration of attacks. Metoprolol is the first drug for which a prophylactic effect in classic migraine has been convincingly demonstrated.     

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。     

Acupuncture in migraine prophylaxis: a randomized sham-controlled trial

The purpose of the present trial was to evaluate semi-standardized acupuncture efficacy in migraine prophylaxis. Twenty-eight subjects with migraine were randomized to the real or sham acupuncture groups. Semi-standardized and standardized minimal acupuncture were used, respectively, in the two groups of patients. They were all treated with 16 acupuncture sessions in 12 weeks. Both groups exhibited similar reductions in: percentage of patients with reduction of migraine>or=40% and >or=50% regarding frequency of migraine attacks, days with migraine, frequency of migraine attacks, average duration of a migraine attack, rate of rescue medication used, average headache severity rate and other parameters compared with the baseline period. Associated symptoms, such as nausea and vomiting, also showed equal estimates in both groups. These findings showed that semi-standardized acupuncture shows no difference from sham acupuncture in preventing migraine attacks.     

西比灵与阿米替林防治偏头痛疗效研究

目的：评价西比灵、阿米替林防治偏头痛的疗效。方法：采用Zung氏焦虑自评量表（SAS）及抑郁自评量表（SDS）评价偏头痛患者的焦虑和抑郁程度。将SAS或SDS评分在40分以上的偏头痛患者随机分为西比灵加阿米替林组（A组）、西比灵组（B组）和阿米替林组（C组）；比较各组间疗效的差异。结果：偏头痛患者中有抑郁者69．3％，焦虑者53．7％。治疗30天后，A组SDS及SAS评分均有所降低（P＜0．05），B组和C组则无显著改善（P＞0．05）。A组及B组治疗前后自身对照在发作次数，持续时间及对生活的影响方面评分差异均有统计学意义（P＜0．05）；C组治疗前后比较则没有统计学意义（P＞0．05）。3组间两两对比以A组防治效果最好，B组次之，C组无效。结论：西比灵加阿米替林对偏头痛有预防效果，且对其伴随的情绪障碍改善也有效。     

Nimodipine versus Flunarizine in Common Migraine: A Controlled Pilot Trial

SYNOPSIS
The effects of Nimodipine and Flunarizine, both calcium-antagonist drugs, in the prevention of common migraine were investigated in a double-blind randomized parallel study. Five patients of the 30 included in the study dropped out because of adverse reactions. Two were treated with Nimodipine and three with Flunarizine. Our results suggest a similar efficacy for both drugs, although Nimodipine seems to have a shorter latency of effect. Nimodipine is a useful new agent for common migraine prevention.     

Flunarizine, a Calcium Channel Blocker, in the Prophylactic Treatment of Migraine

SYNOPSIS
Due to its multiple physiologic effects, including interference with vasoconstriction, protection against brain hypoxia, antihistaminic activity and serotonin antagonism, Flunarizine, a calcium channel blocker, is being considered as an agent for the prophylactic treatment of migraine. Twenty patients with classical or common migraine were treated for 2-6 months with a single nighttime dose of 10 mg of Flunarizine after a 1-3 month placebo stabilization period in a single blind crossover study. Seventeen patients experienced a statistically significant reduction in headache incidence and/or severity (average reduction 53.3%). No clinically significant changes in laboratory analysis, ECG, or physical examination occurred during the treatment period. Side effects included weight gain, dry mouth, fatigue, sleepiness, muscle aches, and paresthesias, and prompted discontinuation of Flunarizine in three patients. We conclude that Flunarizine may be an effective agent in migraine prophylaxis in certain patients. Its low incidence of generally mild side effects may make it preferable to many of the agents currently in use.     

Prophylactic treatment of migraine in children. Part 2. A systematic review of pharmacological trials

The aim of this study was to assess the efficacy of pharmacological prophylactic treatments of migraine in children. Databases were searched from inception to June 2004 and references were checked. We selected controlled trials on the effects of pharmacological prophylactic treatments in children with migraine. We assessed trial quality using the Delphi list and extracted data. Analyses were carried out according to type of intervention. A total of 20 trials were included. Headache improvement was significantly higher for flunarizine compared with placebo (relative risk 4.00, 95% confidence interval 1.60, 9.97). There is conflicting evidence for the use of propranolol. Nimodipine, clonidine, L-5HTP, trazodone and papaverine showed no effect when compared with placebo. All medications were well tolerated and adverse events showed no significant differences. Flunarizine may be effective as prophylactic treatment for migraine in children. Because of the small number of studies and the methodological shortcomings, conclusions regarding effectiveness have to be drawn with caution.     

Effectiveness of lamotrigine in the prophylaxis of migraine with aura: an open pilot study

We report a small open pilot study to evaluate the efficacy of lamotrigine (100 mg/day) in the prevention of migraine with aura attacks. We studied 24 patients affected by migraine with aura with a high frequency of attacks. Following a 1-month run-in period, the patients took lamotrigine for 3 months. Mean attack number per month was reduced from 6.1 +/- 4.1 during the run-in period to 0.7 +/- 1.3 at the 3rd month of treatment (p < 0.0001). In 13 out of 21 patients who completed the study, the attacks were completely abolished at the 3rd month of treatment, while only one patient was completely unresponsive to the drug. Lamotrigine seems worthy of a controlled trial as prophylaxis of a migraine with aura.     

PROPRANOLOL FOR MIGRAINE PROPHYLAXIS

SYNOPSIS
The preventive effect of propranolol on migraine attacks was compared to placebo in a double-blind cross-over trial. Thirty-two patients with serious and prolonged migraine participated in the 12-week study. The effect of propranolol was significantly better than that of placebo. The number of migraine attacks during the propranolol period was reduced in 22 patients (69%), and in 11 of these (34%) a reduction of more than 50% was seen. The intensity of headache was significantly reduced during the propranolol period. The intake of analgesics and preparations containing ergotamine was significantly reduced during the propranolol period also. No serious side effects were noted.