Sublingual Administration of Flunarizine for Acute Migraine: Will Flunarizine Take the Place of Ergotamine?

SYNOPSIS
Clinical effectiveness of 10 mg sublingual flunarizine during 89 headache attacks was observed in 68 chronic headache patients. The study population consisted of 36 patients with migraine, 12 with combined headache, 11 with muscle contraction headache (MCH) and nine with cluster headache. Improved cases, defined as cases showing more than moderate improvement, were 75.0% in the migraine group, 50.0% in the combined headache group, 18.2% in the MCH group and 33.3% in the cluster headache group. The migraine group showed a significantly higher percentage of improved cases than did the MCH group (p<0.002). The group in which subjects received flunarizine within 10 min. from the beginning of headache, showed significantly better improvement than did the group in which subjects were treated after 10 min. (p<0.01). No remarkable side effects were observed except for transient numbness of the tongue and a feeling of sleepiness. Four typical case histories utilizing flunarizine administration, and a case showing recovery from angiospasm after sublingual flunarizine administration during an angiographic examination, are reported. A possible favorable role of flunarizine during migraine attacks is discussed. Double blind studies based on the present observations are necessary.     

Aborting a Migraine Attack: Naproxen Sodium v Ergotamine plus Caffeine

SYNOPSIS
The tolerability and efficacy of naproxen sodium and of ergotamine tartrate plus caffeine (ergotamine) were compared in the treatment of acute migraine attacks and associated symptoms. In this multicenter, double-blind, parallel study of up to six headaches over a 3-month period, patients took naproxen sodium 825 mg, ergotamine 2 mg, or placebo at the time of the first symptom of an attack; 30 minutes later, if necessary, patients repeated naproxen sodium 275 mg, ergotamine 1 mg or placebo, as appropriate. Rescue medication was allowed 30 minutes following the second dose if needed. Active drugs provided notably better relief of head pain than did placebo; 1 hour following the first dose the difference between naproxen sodium and placebo was statistically significant. Naproxen sodium was as efficacious as ergotamine in the relief of migraine attacks and associated symptoms. Relief of vomiting, nausea, photophobia, and motor symptoms favored naproxen sodium over ergotamine; these differences were statistically significant for nausea and motor symptoms. Ergotamine-treated patients reported more complaints and had more severe and longer-lasting complaints than patients on the other two regimens. Overall tolerance ratings by both investigators and patients indicated that naproxen sodium and placebo were tolerated significantly better than ergotamine.     

Flunarizine versus Pizotifen: A Double-Blind Study in the Prophylaxis of Migraine

SYNOPSISThe calcium entry blocker flunarizine was compared with an antiserotonin agent, pizotifen, in the prophylaxis ofmigraine. Thirty-five patients were treated under double-blind conditions for four months. The number of migraineattacks gradually declined in both groups with an eventual mean reduction of 65% and 45% in the flunarizine andpizotifen groups respectively. The efficacy of the former drug developed somewhat faster but no statisticallysignificant differences between the groups were found. Weight gain was the main side effect in both groups. Otherside effects were rare.It is concluded that flunarizine is a useful alternative for the prophylactic treatment of migraine.     

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 in Migraine: A Minireview

Flunarizine is a non-selective calcium antagonist. It distributes preferentially in the adipose tissue and passes the blood brain barrier. Numerous controlled clinical studies have established that flunarizine is efficacious in migraine prophylaxis, including double-blind studies in which the drug was compared with placebo or other antimigraine drugs. To avoid side effects a special schedule or administration is necessary. Flunarizine has no myogenic effect on smooth muscle cells of the vessles. It is said to be the only calcium antagonist able to protect brain cells against hypoxic damage. In addition, the considerable body of information which shows flunarizine capable of directly influencing the central nervous system, suggests that the drug's anti-migraine action may depend on its ability to influence central phenomena.     

Flunarizine, a Calcium Channel Blocker: a New Prophylactic Drug in Migraine

SYNOPSIS
The postulated pivotal role of focal brain hypoxia in the genesis of the migraine attack and the anti-hypoxic properties of flunarizine, have led to the use of the selective calcium-entry blocker in the treatment of migraine. Clinical experience is reviewed. Open findings, confirmed by double-blind placebo-controlled studies and comparisons with pizotifen and cinnarizine, have shown that flunarizine, given at 10 mg daily, is a safe and effective prophylactic drug for both common and classical migraine. Factors determining the efficacy of flunarizine are discussed.     

天麻素联合氟桂利嗪预防偏头痛发作的临床对照研究

目的:评价天麻素联合氟桂利嗪预防偏头痛发作的效果及其安全性.方法:半随机对照临床研究.凡符合入选标准的患者按就诊顺序随机分为两组:试验组予以氟桂利嗪5 mg/次,1次/日,睡前服用;天麻素胶囊50 mg/次,3次/日;连续服用30天;对照组:氟桂利嗪5 mg/次,1次/日,睡前服用,连续服用30天.观察治疗前后头痛发作频率、头痛程度、头痛持续时间变化,评价预防效果.结果:两组治疗后头痛发作频率、头痛程度、头痛持续时间均较治疗前改善(P＜0.05);试验组受试者治疗后头痛发作频率、头痛持续时间的改善情况优于对照组,两者比较有统计学意义(P＜0.05),两组均未发生严重不良反应.结论:天麻素联合氟桂利嗪预防偏头痛发作的效果及安全性良好.     

Comparison Between Venoconstrictor Effects of Sumatriptan and Ergotamine in Migraine Patients

SYNOPSIS
The vasoconstrictor activity of sumatriptan and ergotamine were compared by injecting these drugs in the hand vein of migraine subjects. We used the "venotest method", which permits the evaluation of the venoconstrictor effect of small doses of drugs, acting locally in the hand vein.
Sumatriptan injected at increasing doses in the hand vein provoked contraction only at high doses (500 μg): venoconstriction lasted 5–15 minutes and was similar in intensity and duration to that induced by 0.5-1 μg of 5-hydroxytryptamine (5-HT). Likewise, ergotamine induced contraction only at a dose of 50 μg: this venoconstrictor effect was long lasting (at least I hour). Ergotamine-induced hand vein contraction, almost completely inhibited by ketanserin, seems mediated at least in part by 5-HT ₂ receptors, like the one induced by 5-HT and sumatriptan, already observed in a previous study.
Clinical doses of ergotamine (0.25 mg intramuscular) and of sumatriptan (6 mg subcutaneous) do not provoke hand vein contraction for at least I hour: this could be due to a low activity of these drugs on the 5-HT ₂ vein receptors or a technique that is unsuitable to detect the vasoconstrictor effect of drugs given by the systemic route.
The long lasting venoconstrictor effect of ergotamine may be due to a slow dissociation from receptor sites. The short vasoconstriction induced by sumatriptan could account for the recurrence of headache in many sumatriptan-treated migraine subjects.     

Platelet Activation and Migraine: A Study with Flunarizine

SYNOPSIS
Although in common and classic migraine there is platelet activation both during painful attack and headache-free periods, the role of platelets in migraine pathogenesis is not yet understood. Therefore, in order to investigate the relationship between platelets and migraine pathogenesis, β-thromboglobulin (β-TG) and platelet factor four (PF₄), both platelet-specific alpha granule proteins, were assayed in a group of patients with classic and complicated migraine before and after administration of an anti-migraine drug, flunarizine, at a dose of 10 mg/daily. Blood samples for β-TG and PF₄ assay were collected for ten days in which the patients were headache-free. β-TG and PF₄ plasma levels were elevated in all patients in comparison with control subjects. The patients with complicated migraine showed the highest plasma values. During flunarizine treatment β-TG and PF₄ levels persisted elevated in all patients, although a slight decrease of β-TG plasma levels was observed. This data confirmed, as our previous works, that classic migraine is characterized by platelet activation "in vivo," but that this may not be strictly related to migraine pathogenesis.     

A Case of Hemiplegic Migraine Treated with Flunarizine

SYNOPSIS
A patient with hemiplegic migraine who was treated successfully with flunarizine is presented. A fifteen-year-old boy developed right hemiparesis during several migraine attacks. Regional cerebral blood flow (CBF) measurement using intravenously injected xenon 133 showed that the CBF was about 10-15% lower in left fronto-temporo-parietal regions than that on the contra-lateral side. After the treatment with flunarizine at a dose of 10 mg/day, he has been free of migraine attacks and hemiparesis disappeared. Regional CBF 1 month after treatment showed no decrease in any region of the brain. The findings indicate that flunarizine reversed the neurological deficits by increasing CBF by its vasodilating action.     

Comparison of the Efficacy Between Flunarizine and Nifedipine in the Prophylaxis of Migraine

SYNOPSIS
Background. Several calcium channel blockers have been evaluated in controlled clinical studies and some holdconsiderable promise for future. Efficacy in migraine prophylaxis has been claimed for drugs belonging to all threeclasses of calcium channel blockers (nifedipine-like, verapamil-like, and flunarizine-like), but the extent and quality of theevidence varies, and a comparison of efficacy between different calcium channel blockers has not been reported. Objective. The objective of the study is to assess the comparison of efficacy and safety of flunarizine and nifedipinein migraine prophylaxis. Patients and methods. The study was conducted in a prospective, double-blind, randomized controlled trial, parallelgroup design. 78 patients were studied for a 1-month period during which all patients received placebo followed by a3-month experimental period. Headache response to medication was measured monthly by compilation ofmigraine-scores derived from quantitative data recorded by patients in a daily diary.¹ Student's t-test was used tocompare results from the flunarizine (10 mg) and nifedipine (20 mg) group for each month. Results. Both groups showed a significant reduction in the migraine-scores after 3-months. No significantdifferences were detected between groups, but there was a clinical significantly different reduction of migraine-scoresbetween the groups in the first month after the run-in period (58% vs 38%). It shows that the beneficial effect offlunarizine was more rapidly manifest than that of flunarizine. Tachycardia more frequently occurred in the nifedipinegroup than in the flunarizine treatment group. Conclusion. It concluded that flunarizine is a potentially more useful agent in the prophylaxis of migraine headache.     

Flunarizine in Migraine: A Double-blind Placebo-controlled Study (in a Saudi Population)

We evaluated the effect of flunarizine (Fz) (10 mg/d) on migraine in a double-blind placebo-controlled design. The attacks' frequency, duration, severity and associated symptoms were compared before and after treatment. Forty-two patients completed a three-month trial period; 21 patients received Fz and 21 placebo. Statistical analysis showed no significant difference between Fz and placebo (p > 0.05). In this study Fz was not more efficient than placebo in migraine.     

Low Dose Flunarizine in the Prophylaxis of Migraine

In a period of one year (1990) we selected 40 patients suffering from migraine. For an open randomized study there were 2 groups of patients: the first were treated with 10mg of flunarizine per day and the second with 3 mg per day. The patients were treated for 4 months consecutively. There were 11 drop outs (27.5%): nine for poor compliance and 2 due to side effects. The efficacy of flunarizine in the prophylaxis of migraine was essentially identical in the two dosage groups while the incidence of side effects was considerably reduced in the patients treated with the lower dose.     

Flunarizine and Propranolol in the Treatment of Migraine

The clinical efficacy of flunarizine and of propranolol for the prevention of migraine attacks was assessed in a multicenter double-blind study lasting four months which was preceded by a single-blind placebo period of one month. For both drugs, more than half of the patients judged the effect to be good or very good. When considering the patients' daily logs, both drugs produced a significant reduction of the number of attacks. Propranolol furthermore significantly reduced the severity of attacks and the number of analgesics used during the attacks. In both groups no severe side effects were observed.     

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, 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.     

Naproxen Sodium Versus Ergotamine Tartrate in the Treatment of Acute Migraine Attacks

A double-blind parallel study compared the efficacy and safety of naproxen sodium (NPX) and ergotamine tartrate (ERG) as abortive therapy for acute headache in 79 patients with classical or common migraine. The design study was of the double-blind design. Forty-two patients completed the study. Discontinuation of treatment was generally due to lack of efficacy or adverse reactions. NPX was significantly better than ERG in the overall efficacy of treatment rated by the patients (p less than 004). NPX was comparable to ERG in reducing the severity and duration of the headache and its associated symptoms. In classical migraine, NPX was better than ERG in alleviating the severity of headache. Patients in the NPX group tended to use less rescue medication. There was no significant difference in the frequency of side-effects reported by the patients under NPX or ERG. This study demonstrates that NPX is as safe as ERG, and somewhat more effective in acute migraine attacks (although the difference is not statistically significant) and that migrainous patients tend to prefer NPX to ERG in treating their acute migraine headaches.     

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.