flunarizine and Migraine-Disorders

Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis.. A systematic search in MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo-controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation.. Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06).. Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large-scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.

Topics: Flunarizine; Headache; Humans; Migraine Disorders; Migraine with Aura; Research Design; Transcription Factors

To systematically evaluate the efficacy and safety of acupuncture versus Flunarizine hydrochloride in the treatment of migraine. Four Chinese databases(CNKI, VIP, WanFang, CBM), three English databases(Cochrane Library, EMbase, Medline) and ClinicalTrail.gov were systematically and comprehensively retrieved. The retrieval time was from the establishment of each database to January 8, 2020. Randomized controlled trial(RCT) for acupuncture versus Flunarizine in the treatment of migraine were screened out according to inclusion criteria and exclusion criteria. The included studies were evaluated with the Cochrane bias risk assessment tool. The included studies was conducted by RevMan 5.3, and the outcome indicators were evaluated for evidence quality and strength of recommendation by the GRADE system. A total of 1 033 literatures were retrieved, and 23 studies were finally included. Except for 4 multiarm tests, the total sample size was 1 548, including 785 in acupuncture group and 763 in Flunarizine group. The overall quality of the included studies was not high. Meta-analysis results showed that the acupuncture group was superior to the Flunarizine group in reduction of headache frequency(SMD=-1.00, 95%CI[-1.45,-0.54], P<0.000 1). In reduction of headache intensity, acupuncture group was superior to Flunarizine group(SMD=-1.05, 95%CI[-1.41,-0.68], P<0.000 01). In reduction of headache duration, acupuncture group was superior to Flunarizine group(SMD=-1.42, 95%CI[-1.83,-1.02], P<0.000 1). The acupuncture group was superior to Flunarizine group(MD=-0.17, 95%CI[-0.21,-0.13], P<0.000 01) in reduction of the painkillers taking frequency. The acupuncture group was superior to Flunarizine group(SMD=-0.94, 95%CI[-1.35,-0.52], P<0.000 1) in allevia-tion of paroxysmal symptoms, such as nausea and vomiting. The GRADE system showed that the evidence level of the above indicators was extremely low, and the strength of recommendation was low. As for the occurrence of adverse reactions, the adverse reactions reported in the acupuncture group included in the study were all mild adverse reactions, like drowsiness, subcutaneous bleeding, local pain, subcutaneous hematoma and dizziness needle. The available evidence showed that acupuncture has a better efficacy than Flunarizine hydrochloride in the treatment of migraine in adult patients. However, due to the high bias risk in the included studies, the conclusions of this study shall be adopted with caution, an

Topics: Acupuncture Therapy; Flunarizine; Humans; Migraine Disorders; Treatment Outcome

Based on few clinical trials, flunarizine is considered a first-line prophylactic treatment for migraine in several guidelines. In this meta-analysis, we examined the pooled evidence for its effectiveness, tolerability, and safety. Prospective randomized controlled trials of flunarizine as a prophylaxis against migraine were identified from a systematic literature search, and risk of bias was assessed for all included studies. Reduction in mean attack frequency was estimated by calculating the mean difference (MD), and a series of secondary outcomes-including adverse events (AEs)-were also analyzed. The database search yielded 879 unique records. Twenty-five studies were included in data synthesis. We scored 31/175 risk of bias items as "high," with attrition as the most frequent bias. A pooled analysis estimated that flunarizine reduces the headache frequency by 0.4 attacks per 4 weeks compared with placebo (5 trials, 249 participants: MD -0.44; 95% confidence interval -0.61 to -0.26). Analysis also revealed that the effectiveness of flunarizine prophylaxis is comparable with that of propranolol (7 trials, 1151 participants, MD -0.08; 95% confidence interval -0.34 to 0.18). Flunarizine also seems to be effective in children. The most frequent AEs were sedation and weight increase. Meta-analyses were robust and homogenous, although several of the included trials potentially suffered from high risk of bias. Unfortunately, reporting of AEs was inconsistent and limited. In conclusion, pooled analysis of data from partially outdated trials shows that 10-mg flunarizine per day is effective and well tolerated in treating episodic migraine-supporting current guideline recommendations.

Topics: Databases, Bibliographic; Flunarizine; Histamine H1 Antagonists; Humans; Migraine Disorders; Randomized Controlled Trials as Topic

In migraine attack treatment analgesics such as nonsteroidal anti-inflammatory drugs and triptans can be utilized. The efficacy of acute attack treatment is relevant to prevent migraine chronification. For prophylactic treatment β‑blockers, tricyclic antidepressants, flunarizine, antiepileptics and onabotulinumtoxin A are available. There is evidence that some other substances (e. g. sartans) are also efficacious in this regard. Furthermore, nondrug approaches are essential in migraine therapy. Early education and prophylactic treatment of patients at risk may prevent from medication overuse headache. Noninvasive neuromodulatory approaches as supraorbital or vagal nerve stimulation are emerging methods for prophylactic treatment. Ongoing clinical trials investigate an oral calcitonin gene-related peptide (CGRP) antagonist for acute treatment and several prophylactic monoclonal CGRP or CGRP receptor-antibodies regarding safety, side effects and efficacy as new therapeutic options.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents, Tricyclic; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Combined Modality Therapy; Flunarizine; Humans; Migraine Disorders; Secondary Prevention; Transcutaneous Electric Nerve Stimulation; Tryptamines

Topics: Calcium Channel Blockers; Flunarizine; Humans; Migraine Disorders; Vertigo

Migraine is a complex and multifactorial brain disorder affecting approximately 18% of women and 5% of men in the United States, costing billions of dollars annually in direct and indirect healthcare costs and school and work absenteeism and presenteeism. Until this date, there have been no medications that were designed with the specific purpose to decrease the number of migraine attacks, which prompts a search for alternative interventions that could be valuable, such as acupuncture.. Acupuncture origins from ancient China and encompasses procedures that basically involve stimulation of anatomical points of the body.. This manuscript reviews large and well-designed trials of acupuncture for migraine prevention and also the effectiveness of acupuncture when tried against proven migraine preventative medications.. Acupuncture seems to be at least as effective as conventional drug preventative therapy for migraine and is safe, long lasting, and cost-effective. It is a complex intervention that may prompt lifestyle changes that could be valuable in patients' recovery.

Topics: Acupuncture Therapy; Female; Flunarizine; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Time Factors; Topiramate

Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.. To describe and assess the evidence from controlled trials on the efficacy and tolerability of valproate (valproic acid or sodium valproate or a combination of the two) for preventing migraine attacks in adult patients with episodic migraine.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.. Studies were required to be prospective, controlled trials of valproate taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.. Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between valproate and comparator (placebo, active control, or valproate in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and, in select cases, risk ratios (RRs); we also calculated numbers needed to treat (NNTs). We calculated MDs for Migraine Disability Assessment (MIDAS) scores. We also summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs).. Ten papers describing 10 unique trials met the inclusion criteria. Analysis of data from two trials (63 participants) showed that sodium valproate reduced headache frequency by approximately four headaches per 28 days as compared to placebo (MD -4.31; 95% confidence interval (CI) -8.32 to -0.30). Data from four trials (542 participants) showed that divalproex sodium (a stable combination of sodium valproate and valproic acid in a 1:1 molar ratio) more than doubled the proportion of responders relative to placebo (RR 2.18; 95% CI 1.28 to 3.72; NNT 4; 95% CI 2 to 11). One study of sodium valproate (34 participants) versus placebo supported the latter findings (RR for responders 2.83; 95% CI 1.27 to 6.31; NNT 3; 95% CI 2 to 9). There was no significant difference in the proportion of responders between sodium valproate versus flunarizine (one trial, 41 participants) or between divalproex sodium versus propranolol (one trial, 32 participants). Pooled analysis of post-treatment mean headache frequencies in two trials (88 participants) demonstrates a slight but significant advantage for topiramate 50 mg over valproate 400 mg (MD -0.90; 95% CI -1.58 to -0.22). For placebo-controlled trials of sodium valproate and divalproex sodium, NNHs for clinically important adverse events ranged from 7 to 14.. Valproate is effective in reducing headache frequency and is reasonably well tolerated in adult patients with episodic migraine.

Topics: Adult; Anticonvulsants; Flunarizine; Fructose; Humans; Migraine Disorders; Propranolol; Randomized Controlled Trials as Topic; Topiramate; Valproic Acid

In 1890 four cases of headache associated with visual symptoms and hysterical disorder were described by the French neurologist Babinski as migraine ophthalmique hystérique, or hysterical ophthalmic migraine. Since that time this association has seldom been described, and the possibly high frequency previously reported still remains to be established. This paper has reused Babinski's description and it tries to rehabilitate the syndrome described by the French semiologist across the relatively frequent experience of this type of patients in a public hospital. Also it analyzes the reason of the oblivion of his description.. This study presents a series of 43 cases of headache of the migraine type associated with other symptoms, most consistent with basilar-type migraine according to IHS criteria. Diagnosis of conversion disorder (hysteria) was grounded in the criteria set forth in the DSM-IV.. All patients exhibited one or more manifestations of hysteria (conversion symptoms) during migraine attacks, and some did in the intervals between attacks as well. Details of the headaches, associated symptoms, and hysterical manifestations are discussed. Most patients improved with antimigraine medication. Altered consciousness may have contributed to the onset of hysterical symptoms.. The basilar type migraine associated with conversion symptoms described of systematized form by Babinski, it is not a rare entity. Similar pictures have been described along the history of the medicine. The later silence possibly is due to the historical difficulty in defining accurately the conversión disorders. The Babinskís migraine is a certain well entity and must be recovered for the clinic.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents; Conversion Disorder; Diagnostic and Statistical Manual of Mental Disorders; Electroencephalography; Family; Female; Flunarizine; Hemiplegia; Humans; Hysteria; Male; Mental Disorders; Middle Aged; Migraine Disorders; Pain Measurement; Positron-Emission Tomography; Propranolol; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

Topics: Anticonvulsants; Antidepressive Agents; Antihypertensive Agents; Botulinum Toxins, Type A; Decision Making; Flunarizine; Humans; Migraine Disorders; Neuromuscular Agents; Phytotherapy; Pizotyline; Randomized Controlled Trials as Topic; Referral and Consultation; Vitamins

Calcium channel antagonists have been employed in the prophylactic treatment of migraine. Their major action is the inhibition of Ca2+ influx into smooth muscle cells that is mediated through high voltage-sensitive Ca2+ channels. These drugs had been introduced for the treatment of migraine mainly because of 2 of their effects were considered to be of potential benefit to these patients: their vasodilatory effect and their protective action against the harmful effects of hypoxia on cerebral issue. However, recent studies have provided evidence that in the central nervous system, they directly affect neuronal functions known to be calcium-dependent, such as neurotransmitter synthesis and release, inhibition of cortical spreading depression, and neuronal excitability. Although the exact mechanism of prophylactic effects calcium channel antagonists against migraine attacks remains unknown, alterations in Ca2+ channel function in the central nervous system are believed to play a key role in prophylaxis of migraine.

Topics: Calcium Channel Blockers; Calcium Channels; Drug Administration Schedule; Flunarizine; Humans; Hypoxia, Brain; Migraine Disorders; Neurotransmitter Agents; Piperazines; Premedication; Vasodilation

According to the criteria of the International Headache Society, migraine occurs in approximately 5 to 10% of children. As many as 30% of young patients with migraine experience such frequent and disabling attacks, or have unsatisfactory results and/or experience adverse effects with pharmacologic treatment of acute migraine attack, that daily preventive medications are required. Many studies have investigated the use of antiepileptic drugs in this indication but there is a paucity of placebo-controlled studies. So far, in the setting of migraine with and without aura, only flunarizine and topiramate have proved their efficacy in more than one placebo-controlled study. Uncontrolled studies suggest the possible efficacy of valproic acid, gabapentin, levetiracetam, zonisamide, and magnesium in preventive therapy of childhood periodic syndromes. Most of antiepileptic drugs used in pediatric preventive therapy are well tolerated. The most common adverse events are asthenia and somnolence.

Topics: Anticonvulsants; Child; Flunarizine; Fructose; Humans; Migraine Disorders; Topiramate

According to the principles of evidence-based medicine, the controlled studies on the treatment of idiopathic headache in childhood have been analysed and compiled to treatment recommendations. For the acute treatment of migraine attacks or tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15 mg per kg body weight) are recommended with highest evidence, intranasal sumatriptan (10 to 20 mg) can be given as second choice. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, and valproic acid are recommended. Flunarizine is the drug of first choice in the treatment of migraine-related disorders. No controlled studies are available for the treatment of further headache types. First line methods for the non-drug treatment of headache in childhood are relaxation therapies, biofeedback, and specific training schedules.

Topics: Acetaminophen; Adrenergic beta-Antagonists; Age Factors; Analgesics, Non-Narcotic; Biofeedback, Psychology; Child; Flunarizine; GABA Agents; Headache; Humans; Ibuprofen; Metoprolol; Migraine Disorders; Practice Guidelines as Topic; Propranolol; Relaxation Therapy; Serotonin Receptor Agonists; Sumatriptan; Tension-Type Headache; Valproic Acid; Vasodilator Agents

The clinical use of calcium antagonists (Ca-antagonists) in neurological diseases focuses on 2 main therapeutic fields: (a) For the therapy of migraine flunarizine is the first choice therapy and nimodipine is a second line treatment. With verapamil cluster headache can be treated successfully, flunarizine shows less impressive clinical efficacy. The therapy with flunarizine may be restricted due to the incidence of extrapyramidal disturbances and depressions as known side effects. (b) The therapy of clinical conditions after subarachnoidal bleeding with nimodipine is well established. In the therapy of acute cerebral ischemia the therapeutic efficacy of nimodipine administered orally is not therapeutically proved until now; the intravenous administration of nimodipine offers the risk of acute hypotensive reactions. At present the usefulness of the administration of ca-antagonists in the so-called cerebrovascular insufficiency or dementia and various others cerebral disorders with vertigo could not be demonstrated.

Topics: Brain Ischemia; Calcium Channel Blockers; Cluster Headache; Flunarizine; Humans; Migraine Disorders; Nifedipine; Nimodipine

Calcium antagonists have been proposed for the prophylactic treatment of migraine because of their putative vasodilating antispasmodic effect and of their action against the cellular consequences of brain hypoxia. Published reports of controlled double-blind studies of calcium antagonists for the prophylactic treatment of migraine are reviewed herein. The effectiveness of verapamil, diltiazem, and nifedipine in this indication cannot be considered as firmly demonstrated, when problems with trial design and the amount of available data are taken into account. Nimodipine failed to demonstrate significant effectiveness in migraine with or without an aura. In contrast, the ability of a diphenylpiperazine, flunarizine, to decrease the incidence of migraine attacks in patients with common or classical migraine has been firmly demonstrated, although there is less evidence of this agent's effectiveness on the duration and severity of attacks. The percentage of patients who respond to flunarizine seems comparable to the percentages of propranolol or pizotifen responders. However, flunarizine is associated with unpleasant (weight gain) or severe (extrapyramidal or depressive symptoms) adverse effects which limit its place to that of a second-line drug. Lastly, the analysis of these studies failed to disclose a correlation between calcium movements across the cell membrane and effectiveness for the prevention of migraine attacks. Flunarizine's effect in migraine probably involves monoamine mechanisms which bear no relation to calcium.

Topics: Adrenergic beta-Antagonists; Clinical Trials as Topic; Diltiazem; Flunarizine; Humans; Migraine Disorders; Nifedipine; Nimodipine; Verapamil

The usual drugs for migraine attacks carry risks of increased frequency, resistance to other treatment, drug dependency, and abuse. Ergotamines may also be vascular risk factors. Alternative drugs without these risks would be useful. Flunarizine could be an alternative. Migraine cannot be reduced to molecular pathophysiology; it is a disorder of higher brain functions. Flunarizine exhibits the profile of a psychotropic drug that fits in with this situation. In double-blind placebo-controlled studies, it was shown that 20 mg flunarizine i.v. was superior to placebo in suppressing migraine attacks and was well tolerated. These results should be further investigated, especially concerning reduction of rebound attacks.

Topics: Flunarizine; Humans; Migraine Disorders

Migraine patients suffering from frequent and severe attacks may need prophylactic treatment. Propranolol, a beta-receptor blocker, and flunarizine, a calcium antagonist, are considered to be the most effective compounds for the prophylaxis of migraine. In a number of controlled studies, flunarizine has been shown to reduce the number of migraine attacks significantly. In migraine studies, sedation and weight gain are the most frequent side effects of flunarizine.

Topics: Adolescent; Adult; Calcium Channel Blockers; Child; Child, Preschool; Flunarizine; Humans; Migraine Disorders; Premedication

Apart from the treatment of migraine attacks, prophylaxis may be required when certain criteria of frequency, duration, or severity are met. In a series of placebo-controlled, double-blind studies, the effectiveness of the cerebral calcium antagonist flunarizine (Sibelium) in migraine prophylaxis was shown. In further investigations, the effectiveness of flunarizine was similar to that of propranolol, metoprolol, pizotifene, and methysergide. The side effects described for treatment with flunarizine were somnolence, weight gain, and, in rare cases, depressive mood and extrapyramidal motor disorders. Considering the benefit/risk relation, flunarizine and the beta-adrenergic agents propranolol and metoprolol are now regarded as the drugs of choice. The mechanism of action of flunarizine in migraine prophylaxis is largely unexplained, but the antihypoxic effect of flunarizine is discussed in this context. The search for predicting factors for a successful treatment with flunarizine and the investigation of an injectable solution for the treatment of acute migraine attacks must be left to future research.

Topics: Flunarizine; Humans; Migraine Disorders; Premedication; Randomized Controlled Trials as Topic

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.

Topics: Double-Blind Method; Flunarizine; Humans; Migraine Disorders

Three primary mechanisms have been suggested as an explanation of migraine; a neuronal event, a vascular event and a mechanism focussing on the trigeminal nerve and its supply to intra- and extracranial blood vessels. None of these theories has been adequately proven yet. A neuronal point of impact, rather than a vascular one, seems to be responsible for migraine prophylaxis with calcium antagonists. Primarily vasoactive substances such as nimodipine are not or only marginally effective, whereas flunarizine with a limited vascular activity is effective. Data on other calcium antagonists are insufficient to conclude on a migraine-prophylactic activity. The only calcium antagonist that has been extensively tested for vertigo is flunarizine. In placebo-controlled trials, the drug showed to be effective in labyrinthine vertigo. The mechanism behind this effect is unclear.

Topics: Calcium; Calcium Channel Blockers; Flunarizine; Humans; Migraine Disorders; Vertigo

We administer during 6 months in randomised way dihydroergotamine or flunarizine to 50 children affects of classical or common migraine. A significative improvement was estimated in frequency, intensity and duration of their crisis in 87% with dihydroergotamine and 79% with flunarizine, without significative differences from one to other. Dihydroergotamine was specially effective in children with vegetative lability. The secondary effects, 12% with dihydroergotamine and 20% with flunarizine, were trivial and advantageous even, without the necessity of stop the treatment in not any case.

Topics: Age Factors; Child; Child, Preschool; Dihydroergotamine; Dose-Response Relationship, Drug; Flunarizine; Humans; Migraine Disorders; Parents

Topics: Calcium Channel Blockers; Cerebrovascular Circulation; Flunarizine; Humans; Migraine Disorders

Topics: Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Epilepsy; Female; Flunarizine; Hemiplegia; Humans; Male; Migraine Disorders

Despite ongoing dispute over the pathophysiologic basis of migraine, the vasospastic theory of pathogenesis has brought to the forefront a promising class of new antimigraine agents, the Ca2+ channel antagonists. Voltage-dependent Ca2+ channels, integral membrane proteins that permit extracellular Ca2+ to enter cells down their electrical and concentration gradients, have a universal role in stimulus-response coupling in excitable cells. Thus, they participate in translating electrical excitation into secretory and contractile events. Ca2+ channel antagonists, a structurally diverse group of organic compounds, inhibit ion flux through voltage-dependent Ca2+ channels by binding to specific, channel-associated drug receptor sites and thereby reduce the frequency of channel opening in response to membrane depolarization. Ca2+ channels in cardiac muscle, smooth muscle, and neurons all exhibit high affinity for Ca2+ channel antagonists, although neurons also contain a population of drug-resistant channels. Extensive clinical experience in the use of Ca2+ channel antagonists has accumulated from their application to nonneurologic, especially cardiovascular, disorders. Three such drugs, nifedipine, verapamil, and diltiazem, are currently available in the United States, although none are specifically approved for use in migraine. Other agents, such as nimodipine, are likely to be released in the near future. A large number of clinical studies have now addressed the efficacy of Ca2+ channel antagonists in the prophylaxis of migraine headache. Dihydropyridines (nifedipine and nimodipine), phenylalkylamines (verapamil), diphenylalkylamines (flunarizine), and benzothiazepines (diltiazem) have all been examined, and a beneficial effect has been noted in each case. The limited directly comparative data currently available and the difficulties involved in comparing the results of different studies do not presently support claims of superiority for any single agent. This is an issue that will require attention as these drugs achieve more widespread use in migraine. Existing evidence suggests that flunarizine, verapamil, nifedipine, and nimodipine are effective prophylactic agents in both common and classic migraine. Nifedipine and nimodipine also appear to be valuable for the treatment of cluster headache. Two case reports describing favorable responses to flunarizine in childhood hemiplegic migraine are the only available data concerning the utility of these drugs in "c

Topics: Calcium; Calcium Channel Blockers; Cinnarizine; Diltiazem; Flunarizine; Humans; Ion Channels; Kinetics; Migraine Disorders; Nicotinic Acids; Nifedipine; Nimodipine; Verapamil

According to classic theory, a migraine attack is initiated by cerebrovascular spasm followed by extracranial vasodilatation. Results of recent studies support this theory and suggest that cerebral blood flow during the initial phase of migraine symptoms is, in fact, decreased and this decrease probably leads to ischemia and hypoxia. Cellular hypoxia, in turn, can cause an increase in the flow of calcium from the extracellular fluid to the intracellular space, resulting in calcium overload and cellular dysfunction. Because calcium-channel blockers selectively inhibit the intracellular influx of calcium ions, investigators have begun evaluating the efficacy of these agents for migraine prophylaxis. Nimodipine, a calcium-channel blocker that exhibits selective effects on cerebral vessels, seems to offer protection against the cerebral ischemia and hypoxia presumed to be operative during migraine attacks. In a double-blind, placebo-controlled study, nimodipine decreased the frequency and duration of migraine attacks by at least half in 69% of patients treated with this agent. Comparable reductions in migraine frequency and duration were attained in 58, 51, 41 and 52% of patients treated with methysergide maleate, pizotifen, clonidine hydrochloride and propranolol, respectively. The piperazine derivative flunarizine also has calcium-channel blocking properties. This agent prevents vasospasm in cerebral arteries and protects against cerebral hypoxia. Results of double-blind studies of migraine prophylaxis with flunarizine demonstrate the beneficial effects of this agent, particularly in younger patients. Flunarizine proved to be superior to pizotifen in decreasing the severity of migraine attacks and comparable to pizotifen in decreasing their frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Calcium Channel Blockers; Cinnarizine; Double-Blind Method; Flunarizine; Humans; Hypoxia; Migraine Disorders; Nicotinic Acids; Nimodipine; Vasodilator Agents

Topics: Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Diltiazem; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Nicotinic Acids; Nifedipine; Nimodipine; Verapamil

Flunarizine is a 'selective' calcium entry blocker with a similar chemical structure and pharmacological profile to the related compound, cinnarizine. However, in contrast to cinnarizine it has a long plasma half-life and need only be given once a day. The majority of therapeutic trials in the prophylaxis of migraine, occlusive peripheral vascular disease and vertigo of central or peripheral origin have been placebo-controlled, and have shown that the drug produces significantly greater beneficial effects than placebo as evaluated by subjective and objective criteria. A small number of comparative studies have shown flunarizine to be at least as effective as pizotifen in migraine prophylaxis, and in a longer term study as effective as cinnarizine in vertigo of central origin. However, it has not been compared with other drugs which may be useful in these areas, such as methysergide in migraine prophylaxis, some antihistamines or phenothiazines in vertigo, or (understandably at this stage of its evolution) with surgical revascularisation in severe occlusive peripheral vascular disease. In preliminary placebo-controlled studies there was some evidence that flunarizine may improve impaired cognitive function in patients with cerebrovascular disorders, but such findings need further confirmation in additional carefully conducted studies. With a very long half-life, flunarizine may be given once daily; and drowsiness, the main side effect, can be minimised by taking the daily dose in the evening. Thus, it appears that flunarizine will offer a useful alternative in some therapeutic areas that can be difficult to manage with previously available therapy. However, a definitive statement on its relative place in therapy of such conditions must await a few well-controlled comparative studies.

Topics: Adult; Age Factors; Aged; Animals; Anti-Arrhythmia Agents; Anticonvulsants; Blood; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Flunarizine; Histamine H1 Antagonists; Humans; Kinetics; Migraine Disorders; Piperazines; Vascular Diseases; Vasodilator Agents; Vertigo

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Migraine Disorders; Piperazines; Pizotyline; Time Factors

The incidence rate for migraine is 12% worldwide, and recurrence is common, which seriously affects the physical and mental health of patients.. To observe the clinical effect of Shallow Puncture and More Twirling method of acupuncture in treating migraine and its impact on serum 5-HT and β-EP.. A total of 76 patients with migraine were randomized into a control group and acupuncture group with 38 cases in each. In the control group, patients were orally administered flunarizine hydrochloride before sleep, 2 capsules once daily for 4 weeks. In the acupuncture group, Shallow Puncture and More Twirling method was adopted for the acupoints of Sizhukong (SJ 23), Toulinqi (GB 15) Shuaigu (GB 8), Xuanlu (GB 5), Fengchi (GB 20), Waiguan (SJ 5), Zulinqi (GB 41). Patients were given acupuncture 3 times per week for 4 weeks. Then, the total VAS (Visual Analogue Scale) scores, composite score of migraine, serum level of 5-HT and β-EP, and the clinical efficacy differences were observed before and after treatment and the side-effects were recorded among the two groups.. The total VAS scores and composite score of migraine were significantly reduced among both groups after the treatment (P< 0.05), and the serum level of 5-HT and β-EP was significantly improved (P< 0.05). Compared with control group, the acupuncture group reported lower results in VAS score and migraine composite score (P< 0.05), and higher results in serum 5-HT and β-EP level (P< 0.05). The acupuncture group with shallow puncture and more twirling method showed a total effective rate of 86.5%, which is higher than the control group (78.4%). The difference is statistically significant (P< 0.05).. Shallow Puncture and More Twirling method was superior to flunarizine hydrochloride in the treatment of clinical symptoms of migraine. Acupuncture also increases the serum level of 5-HT and β-EP in migraine.

Topics: Acupuncture Therapy; Flunarizine; Humans; Migraine Disorders; Punctures; Serotonin; Treatment Outcome

Nutraceuticals like alpha-lipoic acid (ALA) may have potential benefits as prophylactic agents for adolescent migraine, with fewer adverse events than existing medications. The present study was conducted to evaluate the safety and efficacy of add-on ALA for prophylaxis in adolescent migraine. A randomized, open-label, add-on clinical trial was conducted with 60 adolescent migraineurs, who were randomized to receive flunarizine or flunarizine with an add-on ALA. A clinical evaluation of the frequency and severity of migraine, responder rate, Pediatric Migraine Disability Assessment (PedMIDAS) scoring, serum thiol, and serum calcitonin gene-related peptide (CGRP) was performed both at baseline and following 12 weeks of treatment. The frequency of acute attacks of migraine decreased significantly (P = .001) in the test group compared with the control group. The responder rate was found to be significantly higher (80%) in the test group than in the control group (33.3%) (P = .001). The mean monthly migraine headache days in the test group showed a significant reduction (-7.7 days, 95%CI -9.1 to -6.3 days; P = .010). The severity of acute migraine attacks (mild, moderate, severe) also showed a significant reduction in the test group (P = .001). PedMIDAS scores showed significant improvement in the test group (P = .021), in comparison with the control group. Serum thiol levels were significantly increased in the test group (18 mmol/L, 95%CI 13.5 to 36.1 mmol/L; P = .001). Serum CGRP levels showed a significant reduction with adjunctive ALA therapy (-122.4 pg/mL, 95%CI -142.3 to -89.0 pg/mL; P = .006). Add-on ALA with flunarizine as a prophylactic agent for migraine in adolescents can improve clinical outcomes by improving clinical and biochemical parameters.

Topics: Adolescent; Analgesics; Calcitonin Gene-Related Peptide; Child; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Sulfhydryl Compounds; Thioctic Acid; Treatment Outcome

This study aimed to investigate the extent of autonomic nervous system dysfunction in patients with chronic migraine using heart rate variability analysis. In addition, we explored the potential association between heart rate variability and treatment outcomes in patients receiving preventive treatment.. In this cross-sectional and prospective study, we compared heart rate variability profiles in 81 preventive-naïve chronic migraine patients and 58 healthy controls. In addition, treatment responses of patients, who received a 12-week treatment with flunarizine, were assessed in relation to baseline heart rate variability.

Topics: Cross-Sectional Studies; Flunarizine; Heart Rate; Humans; Migraine Disorders; Prospective Studies; Treatment Outcome

To investigate the impact of topiramate versus flunarizine on the non-headache symptoms (NHS) of migraine, and to observe the changes of dopamine (DA) and prolactin (PRL) before and after prophylactic treatment.. Sixty-six episodic migraine patients were enrolled and randomized 1:1 to receive either flunarizine or topiramate treatment. Clinical characteristics and NHS associated with migraine were investigated before and after prophylactic treatment. The DA and PRL levels were also determined before and after prophylactic treatment.. The NHS of migraine in the two groups were significantly better after treatment than before treatment in premonitory phase (PP), headache phase (HP), and resolution phase (RP). The NHS in the two groups had no significant difference in PP, HP, and RP before and after treatment. In the flunarizine group, the PRL content after treatment was significantly higher than that before treatment (. The two classical prophylactic drugs of migraine were significantly effective in treating the NHS of migraine, but there was no significant difference between the two drugs. The DA-PRL axis may be involved in the underlying mechanism of the flunarizine treatment for the NHS of migraine.

Topics: Dopamine; Flunarizine; Fructose; Headache; Humans; Migraine Disorders; Topiramate

To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver. After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (. Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver

Topics: Acupuncture Points; Electroacupuncture; Flunarizine; Humans; Liver; Migraine Disorders

This study is aimed to access the efficacy and safety of combination therapy of flunarizine plus transcutaneous supraorbital neurostimulation (tSNS) compared with either flunarizine or tSNS alone for migraine prophylaxis.. Patients with episodic migraine were enrolled and randomized into 3 groups. Flunarizine 5 mg per day, or tSNS for 20 minutes daily or combination of both were prescribed consecutively for 3 months. The primary outcome measures were changes in migraine days and 50% responder rate of monthly migraine days. Secondary outcome measures were the changes in migraine intensity and intake of rescue medication. Finally, satisfaction to treatment and adverse effect were evaluated as well.. A total of 154 were randomized and included in the analysis. After 3 months, the monthly migraine days were decreased in 3 groups and more significant in the combination group. The 50% responder rate was significantly higher (78.43%) in the combination therapy than monotherapy of flunarizine (46.15%) or tSNS (39.22%) alone. Greater reduction of migraine intensity and intake of rescue medication was observed in combination group. There was no difference of adverse events between flunarizine group and combination group (P = .89).. Adding tSNS to flunarizine can improve the therapeutic efficacy of migraine prophylaxis without increasing the adverse effects. In addition, tSNS is effective and safe for migraine treatment and can be a valid option for migraineurs who are reluctant to take oral medications or for patients who experience a low-migraine frequency and/or intensity that prophylactic therapy is not indicated but desire to acquire medical intervention.

Topics: Adult; Combined Modality Therapy; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Transcutaneous Electric Nerve Stimulation; Vasodilator Agents

This study aimed to explore the effectiveness of acupuncture combined with tuina therapy in patients with migraine.. A prospective, randomized controlled assessor-blind clinical trial was performed between January 2017 and May 2018, and 135 patients were assigned into acupuncture combined with tuina (A), acupuncture (B), and control (flunarizine hydrochloride) (C) groups, each with 45 patients. Treatments were performed for 12 weeks and a 4-week follow-up. Frequency of attacks, severity of pain, duration of migraine, associated symptoms, patient-reported outcome (PRO) scores, and frequency of analgesic consumption were assessed.. The total effective rate was 95.6, 88.9, and 75.6% for group A, B, and C, respectively, with a significant reduction in attack frequency, severity of pain, duration of migraine, and associated symptoms at post-treatment and follow-up compared to pre-treatment. The PRO scores and frequency of analgesic consumption were significantly improved (group A, p < 0.01; groups B and C, - p < 0.05). The differences in pre-/post-treatment and in pre-treatment/follow-up in groups A and B were significantly improved compared to group C (A vs. C, p < 0.01; B vs. C, A vs. B, p < 0.05). No significant adverse events occurred.. Acupuncture combined with tuina could significantly increase the therapeutic effect of acupuncture in migraine treatment.. Hintergrund: Mit der vorliegenden Studie sollte die Wirksamkeit von Akupunktur in Kombination mit einer Tuina-Therapie bei Patienten mit Migräne beurteilt werden. Methoden: Zwischen Januar 2017 und Mai 2018 wurde eine prospektive, randomisierte, kontrollierte klinische Studie mit verblindetem Untersucher durchgeführt. Für die Studie wurden 135 Patienten einer von drei Behandlungsgruppen mit jeweils 45 Patienten zugewiesen: Akupunktur in Kombination mit Tuina-Therapie (Gruppe A), Akupunktur (Gruppe B) oder Kontrolle (Flunarizinhydrochlorid) (Gruppe C). Die Behandlung erfolgte jeweils über 12 Wochen und die Follow-up-Dauer betrug 4 Wochen. Dabei wurden die Anfallshäufigkeit, Schmerzintensität, Dauer der Migräne, Begleitsymptome, Scores der Patientenbeurteilungen sowie die Häufigkeit der Analgetika-Einnahme beurteilt. Ergebnisse: Die Gesamt­wirksamkeitsraten betrugen 95,6%, 88,9% und 75,6% für Gruppe A, B und C, wobei hinsichtlich der Anfallshäufigkeit, Schmerzintensität, Migränedauer und Begleit­symptome nach der Behandlung und während des Follow-ups ein signifikanter Rückgang gegenüber der Situation vor der Behandlung zu beobachten war. Die Scores der Patientenbeurteilungen und die Häufigkeit der Analgetika-Einnahme verbesserten sich signifikant (Gruppe A, p < 0,01; Gruppe B und C, p < 0,05). Die prä-/post-therapeutischen Unterschiede sowie die Unterschiede zwi­schen der Situation vor der Therapie und während des Follow-ups fielen in Gruppe A und B gegenüber Gruppe C signifikant besser aus (A vs. C, p < 0,01; B vs. C, A vs. B, p < 0,05). Es traten keine signifikanten unerwünschten Ereignisse auf. Schlussfolgerung: Akupunktur in Kombination mit Tuina-Therapie kann die therapeutischen Effekte der Akupunktur in der Migräne-Behandlung signifikant verbessern.

Topics: Acupuncture Therapy; Adolescent; Adult; Aged; Analgesics; Combined Modality Therapy; Female; Flunarizine; Humans; Male; Massage; Medicine, Chinese Traditional; Middle Aged; Migraine Disorders; Treatment Outcome; Vasodilator Agents; Young Adult

To test the effects of Nimodipine plus Yufeng Ningxin tablets on frequent migraine.. Two hundred forty-two patients with frequent migraine were divided into the control group with those consuming Flunarizine (120 cases) and the treatment group with those consuming Nimodipine plus Yufeng Ningxin tablets (122 cases). The course of frequent migraine treatment lasted 7 weeks. The number of migraine days, visual analogue scale (VAS) score, and response rate were measured.. There was significant difference in the cure rate as the Nimodipine plus Yufeng Ningxin tablets group compared with the Flunarizine group (78.7 vs. 21.7%; p < 0.001). Fewer migraine days and VAS score were observed in the treatment group when compared with the control group (p < 0.05). Nimodipine plus Yufeng Ningxin tablets were superior to Flunarizine in terms of the response rate at week 7 (p < 0.05).. Due to its high cure rate, treatment with Nimodipine plus Yufeng Ningxin tablets is recommended to control frequent migraine, and this hypothesis needs to be confirmed through further studies conducted on a more extensive population.

Topics: Adult; Calcium Channel Blockers; Double-Blind Method; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Flunarizine; Humans; Isoflavones; Male; Migraine Disorders; Nimodipine; Treatment Outcome; Young Adult

Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10 mg/d flunarizine for CM prophylaxis as compared with 50 mg/d topiramate.. We conducted a prospective, randomized, open-label, blinded-endpoint trial. Patients with CM were randomized to flunarizine and topiramate treatment. The primary outcomes assessed were the reductions in the total numbers of headache days and migraine days after 8 weeks of treatment. Secondary outcomes were reductions in the numbers of days of acute abortive medication intake and acute abortive medication tablets taken, and the 50% responder rate.. Sixty-two subjects were randomized (n=31/group). Patients treated with flunarizine showed significant reductions in the numbers of total headache days (-4.9 vs -2.3, P=.012) and migraine days (-4.3 vs -1.4, P=.001) compared with those treated with topiramate. Patients treated with flunarizine also showed significant reductions in the numbers of days of acute abortive medication intake (-2.3 vs -0.2, P=.005) and acute abortive medication tablets taken (-4.6 vs -0.5, P=.005) and had a higher 50% responder rate in terms of total headache days (58.6% vs 25.9%, P=.013) and migraine days (75.9% vs 29.6%, P=.001), compared with topiramate-treated patients. Flunarizine was generally well tolerated and had a safety profile comparable to that of topiramate.. Our results suggest that, in an 8-week study, 10 mg/d flunarizine is more effective than 50 mg/d topiramate for CM prophylaxis.

Topics: Adult; Anticonvulsants; Double-Blind Method; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate

Topics: Anticonvulsants; Betahistine; Flunarizine; Humans; Life Style; Migraine Disorders; Vertigo

The primary objective of this study was to assess whether Zhengtian Capsule was non-inferior to flunarizine in efficacy and safety profile for prevention of migraine in adults.. This was a double-dummy, double-blind, multicenter, positive drug (flunarizine), parallel randomized controlled, non-inferior clinical trial. Patients (n = 360) were randomized in a 1:1 to receive either Zhengtian Capsule or flunarizine, including 12 weeks' intervention and 4 weeks' follow-up. The primary outcome measure was responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period). The secondary outcome measures included migraine attack frequency, the number of migraine days, pain evaluated by visual analogue scale (VAS) score, duration of migraine attacks, the times of using analgesics, patient-reported outcome (PRO) measure of migraine and the scores of short-form 36 Health Survey Scale (SF-36). Weight variation in both groups was also evaluated. Adverse events were monitored throughout the trial.. Zhengtian Capsule was non-inferior to flunarizine in responder rate at week 12 and follow-up period (P = 0.002, P < 0.001). There was fewer migraine days in Zhengtian Capsule group at follow-up period compared with flunarizine (P = 0.001). For the total duration of migraine attacks, there was significant group difference at week 4 which favored the control group (P = 0.009). For the total score of PRO scale, there was statistical difference between the two groups at follow-up period (P = 0.021). There were also group differences between the two groups in the dimensions of somatization symptoms at week 4 (P = 0.022) and functional status at week 12 and follow-up period (P < 0.001, P < 0.001). However, there were no significant differences between the two groups in migraine attack frequency, VAS scores reduction, consumption of acute pain drugs and the dimension scores of SF-36 at any time interval of the treatment period (P > 0.05). No severe adverse events occurred in the trial. Flunarizine was found associated with a weight gain.. Zhengtian Capsule was non-inferior to flunarizine with regard to the primary endpoint. In addition, it could reduce migraine days and improve the functional status and somatization symptoms of migraine patients with good safety profile.. This trial was registered at Chinese Clinical Trial Register (ChiCTR), ChiCTR-TRC-13004412.

Topics: Adult; Analgesics; Double-Blind Method; Drugs, Chinese Herbal; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Pain Measurement

Migrainous vertigo is a common cause of dizziness presenting to an otorhinolaryngology/otoneurology clinic. Although it causes a substantial burden to the individual and society there are no randomized controlled trails on prophylactic medication for this condition. Flunarizine, a calcium channel blocker has been used effectively in both migraine and vestibular conditions. This randomized control trial was undertaken in a tertiary academic referral center to evaluate the efficacy of flunarizine in patients with migrainous vertigo when compared to non-specific vestibular treatment of betahistine and vestibular exercises. The effect of flunarizine on two particularly disabling symptoms of vertigo and headache was studied. A total of 48 patients who were diagnosed with definitive migrainous vertigo completed the study of 12 weeks duration. Patients in arm A received 10-mg flunarizine daily along with betahistine 16 mg and paracetamol 1 gm during episodes, and arm B received only betahistine and paracetamol during episodes. Symptom scores were noted at the start of the study and at the end of 12 weeks. Analysis of the frequency of vertiginous episodes showed a significant difference between arm A and arm B (p = 0.010) and improvement in severity of vertigo between the two groups (p = 0.046). Headache frequency and severity did not improve to a significant degree in arm A as compared to arm B. The main side effects were weight gain and somnolence and this was not significantly different between the two groups. Flunarizine (10 mg) is effective in patients with migrainous vertigo who suffer from considerable vestibular symptoms.

Topics: Acetaminophen; Adolescent; Adult; Aged; Betahistine; Calcium Channel Blockers; Disorders of Excessive Somnolence; Drug Therapy, Combination; Female; Flunarizine; Histamine Agonists; Histamine Antagonists; Humans; Male; Middle Aged; Migraine Disorders; Vertigo; Weight Gain; Young Adult

To determine the minimum duration of migraine prophylaxis, after patients become pain-free. Migraine patients diagnosed according to criteria of International Classification of Headache Disorders-2 were treated prophylactically. After becoming pain-free, they were divided into two equal groups: in group 1, prophylaxis was maintained for another 12 months and in group 2, for 24 months. Each group was followed for more three years after prophylaxis period. Of the 50 patients, 39 (78%) were female and 11 (22%) were male. The age ranged from 18 to 50 years. Before treatment, the attack frequency for groups 1 and 2 was, respectively, 16.3 ± 12.8 and 16.4 ± 11.8 days per month (p = 0.769). Patients in groups 1 and 2 have become pain-free, respectively, with 21.4 ± 11.2 and 16.8 ± 9.9 months (p = 0.161). During three years without treatment, groups 1 and 2 maintained an annual frequency of respectively 3.2 and 0.5 headache days. Of the patients in group 2, 76.0% (19/25) remained pain-free during follow-up, versus 44.0% (11/25) of group 1, with a significant difference (p=0.001). The best results were obtained when migraine prophylaxis was maintained for 24 months after patients became pain-free.

Topics: Adolescent; Adult; Atenolol; Dose-Response Relationship, Drug; Female; Flunarizine; Humans; International Classification of Diseases; Male; Middle Aged; Migraine Disorders; Nortriptyline; Prospective Studies; Time Factors; Treatment Outcome; Vasodilator Agents; Young Adult

To investigate the preventive effect of behavioral therapy plus flunarizine in children with migraine.. Ninety pediatric patients with migraine between January 2011and January 2014 were randomly divided into treatment group (45 cases) and control group (45 cases). The treatment group received behavioral therapy in addition to oral flunarizine, while the control group received oral flunarizine alone. All patients were followed up for 3 months to evaluate the therapeutic effect by the Pediatric Migraine Disability Assessment Score (PedMIDAS) and improved Bussone headache index.. There were no significant differences in PedMIDAS (P>0.05) and improved Bussone headache index (P>0.05) between the control and treatment groups before treatment. Significant differences were observed in PedMIDAS (16±8 vs 20±10; P<0.05) and improved Bussone headache index (25±18 vs 37±21; P<0.05) between the two groups after 3 months of treatment.. Preventive treatment of behavioral therapy plus oral flunarizine shows a better clinical efficacy than oral flunarizine alone in children with migraine and holds promise for clinical application.

Topics: Adolescent; Behavior Therapy; Child; Combined Modality Therapy; Female; Flunarizine; Humans; Male; Migraine Disorders

Migraine is a common neurological problem, which accounts for large morbidity and disability. Non-steroidal anti-inflammatory agents and triptans are mainly used to terminate the attack of moderate to severe migraine. This study compared the safety, efficacy and pharmaco-economics of rizatriptan (5HT(IB/ID) agonist) versus conventional therapy (paracetamol 500 mg + metoclopramide 10 mg + flunarizine 10 mg + alprazolam 0.5 mg). In this study, drug combinations used in conventional therapy was indigenously designed by the neurologist. Rizatriptan was found more efficacious than conventional therapy in terminating an attack of migraine and its' associated symptoms but looking into the contra-indications, side-effects and cost of the former there has been limitation in its prescription as well as the use.

Topics: Acetaminophen; Adolescent; Adult; Aged; Alprazolam; Analgesics, Non-Narcotic; Female; Flunarizine; Humans; Male; Metoclopramide; Middle Aged; Migraine Disorders; Prospective Studies; Serotonin Receptor Agonists; Treatment Outcome; Triazoles; Tryptamines; Vasodilator Agents; Young Adult

Topiramate and onabotulinumtoxin A have proven to be effective in chronic migraine with or without medication abuse according to recent criteria of the International Headache Society's Headache Classification.. To show that flunarizine is as effective as topiramate in cases of chronic migraine without medication abuse.. We conducted a prospective, non-randomised, comparative study of two groups of patients paired by age and sex, with chronic migraine without abuse, who had been treated preventively for the first time with topiramate or flunarizine.. Forty patients treated with flunarizine were assigned a patient of their same sex and age who was being treated with topiramate. The mean rate of reduction in intense migraines in the topiramate group was 59% and in the flunarizine group, 58.5% (p = 0.9444); the responder rate at four months of treatment did not show any significant differences either, the figures being 75% for topiramate and 70% for flunarizine (p = 0.6236). The mean reduction of other headaches in the topiramate group was 57% and in the flunarizine group, 64% (p = 0.4261); the responder rate at four months of treatment was similar in the two groups: 76%. The percentage of dropouts from treatment was higher with topiramate (19.5%) than with flunarizine (10%) (p = 0.3493). No serious side effects occurred in either of the groups. In all, 78.9% of the patients who took topiramate said they were satisfied with the drug versus 75% of those in the flunarizine group (p = 0.7903).. Flunarizine proved to be as effective as topiramate in the treatment of chronic migraine without medication abuse.. Estudio comparativo de la efectividad del topiramato y la flunaricina en series independientes de pacientes con migraña cronica sin abuso de medicacion.. Introduccion. El topiramato y la onabotulinumtoxina A han mostrado ser eficaces en la migraña cronica con o sin abuso de farmacos segun los criterios recientes de la Clasificacion de Cefaleas de la Sociedad Internacional de Cefaleas. Objetivo. Demostrar que la flunaricina es tan efectiva como el topiramato en la migraña cronica sin abuso de farmacos. Pacientes y metodos. Estudio prospectivo, no aleatorizado, comparativo de dos grupos de pacientes con similar edad y sexo, con migraña cronica sin abuso, tratados preventivamente por primera vez con topiramato o flunaricina. Resultados. A 40 pacientes tratados con flunaricina se les asigno un paciente del mismo sexo y edad tratado con topiramato. La media de reduccion de las migrañas intensas en el grupo del topiramato fue del 59% y en el grupo de la flunaricina, del 58,5% (p = 0,9444); la tasa de respondedores al cuarto mes de tratamiento tampoco mostro diferencias significativas, ya que fue del 75% para el topiramato y del 70% para la flunaricina (p = 0,6236). La media de reduccion de otras cefaleas en el grupo del topiramato fue del 57%, y en el grupo de la flunaricina, del 64% (p = 0,4261); la tasa de respondedores al cuarto mes de tratamiento fue del 76%, similar en ambos grupos. El porcentaje de abandonos del tratamiento fue mayor con el topiramato (19,5%) que con la flunaricina (10%) (p = 0,3493). En ninguno de los dos grupos hubo efectos adversos graves. Un 78,9% de los pacientes que tomo topiramato presento satisfaccion con el farmaco frente al 75% del grupo de la flunaricina (p = 0,7903). Conclusion. La flunaricina mostro ser tan efectiva como el topiramato en el tratamiento de la migraña cronica sin abuso de farmacos.

Topics: Adult; Calcium Channel Blockers; Chronic Disease; Cognition Disorders; Fatigue; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Dropouts; Patient Satisfaction; Prospective Studies; Topiramate; Treatment Outcome

The objective of this study was to observe the efficacy, safety, and side effects of a combination of flunarizine plus topiramate compared with either flunarizine and or toparamate alone for migraine prophylaxis.. Out of 150 patients with migraine recruited into the study and randomly assigned to one of three conditions, 126 completed the trial in their group: flunarizine (39), topiramate (44), and flunarizine plus topiramate (43). Patient information was assessed at enrollment and at follow-up visits at the end of months 1-3, 6, 9, and 12. The primary measure of efficacy reduction in mean monthly migraine frequency of at least 50% as compared with baseline. Secondary efficacy parameters included reduction in mean monthly migraine days and severity of headache. Side effects were compared in the three groups by recording adverse reactions and weight changes.. The proportion whose monthly headache frequency decreased more than 50% was 66.7% (26/39) in the flunarizine group, 72.7% (32/44) in the topiramate group and 76.7% (33/43) in the combination group, respectively (P=0.593). The mean monthly days and severity of headache in the three groups also declined and was more significant in the flunarizine plus topiramate group than in the flunarizine group and the topiramate group (P<0.05). In the flunarizine group, the average weight change was 0.6kg. Topiramate was associated with a mean weight loss was of -0.9kg in the topiramate group and -0.2kg in the flunarizine plus topiramate group.. Flunarizine, topiramate, and the combination of flunarizine with topiramate are all effective and have good tolerability in migraine prophylaxis. Adding topiramate to flunarizine may reduce the latter's impact on body weight.

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Female; Flunarizine; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Treatment Outcome; Young Adult

This study was aimed to verify changes in the levels of hypothalamic neuropeptides in migraineurs under preventive treatment with amitryptiline and flunarizine. Thirty-nine migraine patients with a body mass index <25 kg/m(2) and without endocrinological or metabolic diseases were assigned to two treatment groups, one receiving amitryptiline, the other flunarizine, for 3 months. Orexin-A, orexin-B and neuropeptide-Y plasma levels were measured at the basal time, at the 1st, 2nd and 3rd months of preventive treatment.. A statistically significant reduction in plasma orexin-A and orexin-B levels emerged in both groups. Conversely, plasma neuropeptide-Y levels were markedly increased, with the highest levels at the 2nd and 3rd months, in both patient groups. Orexin-A levels were also negatively correlated to weight gain in both groups during the treatment period.. These results suggest that changes in the levels of hypothalamic orexinergic peptides may contribute to body weight increase occurring in migraineurs during amitryptiline or flunarizine prophylactic treatment.

Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Female; Flunarizine; Humans; Hypothalamus; Male; Middle Aged; Migraine Disorders; Neuropeptides; Pilot Projects; Radioimmunoassay; Weight Gain; Young Adult

Insufficient clinical trial data were available to prove the efficacy of acupuncture for migraine prophylaxis. A multicenter, double-dummy, single-blinded, randomized controlled clinical trial was conducted at the outpatient departments of acupuncture at 5 hospitals in China to evaluate the effectiveness of acupuncture. A total of 140 patients with migraine without aura were recruited and assigned randomly to 2 different groups: the acupuncture group treated with verum acupuncture plus placebo and the control group treated with sham acupuncture plus flunarizine. Treated by acupuncture 3 times per week and drugs every night, patients from both groups were evaluated at week 0 (baseline), week 4, and week 16. The primary outcome was measured by the proportion of responders (defined as the proportion of patients with a reduction of migraine days by at least 50%). The secondary outcome measures included the number of migraine days, visual analogue scale (VAS, 0 to 10 cm) for pain, as well as the physical and mental component summary scores of the 36-item short-form health survey (SF-36). The patients in the acupuncture group had better responder rates and fewer migraine days compared with the control group (P<.05), whereas there were no significant differences between the 2 groups in VAS scores and SF-36 physical and mental component summary scores (P>.05). The results suggested that acupuncture was more effective than flunarizine in decreasing days of migraine attacks, whereas no significantly differences were found between acupuncture and flunarizine in reduction of pain intensity and improvement of the quality of life.

Topics: Acupuncture Therapy; Adolescent; Adult; Aged; China; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Outcome Assessment, Health Care; Pain Measurement; Prospective Studies; Retrospective Studies; Single-Blind Method; Treatment Outcome; Vasodilator Agents; Young Adult

To investigate the therapeutic effect and safety of acupuncture at points of The Liver and Gallbladder Meridians for treatment of migraine.. Multi-central, randomized and controlled trial was used and 253 cases of migraine were divided into an acupuncture group and a western medicine group. The acupuncture group was treated with acupuncture at points of The Liver and Gallbladder Channels with Taichong (LR 3), Yang-lingquan (GB 34), Fengchi (GB 20), Ququan (LR 8) selected as main points, and the western medicine group with oral administration of Flunarizine tablets for 4 therapeutic courses. The total therapeutic effects 3 and 6 months after the treatment, the scores of various symptoms of migraine before and after treatment, and the stability of therapeutic effect in one-year following-up survey were observed in the two groups.. After treatment, mean times and duration of the headache attack were significantly improved in the two groups (all P < 0.01) with the acupuncture group better than the western medicine group (P < 0.05). The total effective rates for stopping pain after treatment, 3 months and 6 months after treatment in the acupuncture group were 93.0%, 93.0% and 87.7%, respectively, which were better than 85.6%, 86.5% and 69.2% in the western medication group (all P < 0.01). One year later, the stability of the therapeutic effect in the acupuncture group was better than that in the western medicine group (P < 0.05); the adverse reaction and the compliance in the acupuncture group were significantly superior to those in the western medicine group.. Acupuncture at points of The Liver and Gallbladder Meridians for treatment of migraine is safe, effective, and with stable long-term therapeutic effect.

Topics: Acupuncture Points; Acupuncture Therapy; Administration, Oral; Adolescent; Adult; Aged; Female; Flunarizine; Gallbladder; Headache; Histamine H1 Antagonists; Humans; Liver; Male; Meridians; Middle Aged; Migraine Disorders; Treatment Outcome; Young Adult

To evaluate the effect of different migraine prophylaxis medications on subject responsiveness to almotriptan.. There is evidence supporting an increase of responsiveness of symptomatic medications for migraine attacks by some prophylactic treatments although this has not been probed.. A total of 345 patients (230 women, mean age 37.3) with episodic or chronic migraine were classified according to the prophylaxis they were taking in the following groups: (1) no prophylactic medication; (2) propranolol; (3) topiramate; (4) flunarizine. Decrease in Analogical Visual Scale and pain-free at 2 hours after almotriptan intake was assessed at 2 months. Side effects and discontinuation or treatment were also assessed.. Headache severity was reduced 4.2 in control group, 5.3 in propranolol group, 4.1 in topiramate group, and 4.0 in flunarizine group, whereas pain-free status was achieved in 37.3%, 48.7%, 36.1%, and 38.1% respectively. These two parameters were statistically significative between propranolol and control groups. Side effects were similar in all groups.. Our results displayed a higher efficacy of almotriptan in propranolol group and we hypothesized it may be due to a common mechanism of action at serotoninergic receptors.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Anticonvulsants; Calcium Channel Blockers; Drug Interactions; Drug Therapy, Combination; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Pain Measurement; Propranolol; Serotonin Receptor Agonists; Topiramate; Treatment Outcome; Tryptamines; Young Adult

The aim of this study was to evaluate the prevalence of functional gastrointestinal disorders (FGIDs) in children with migraine headache and the effects of flunarizine on gastrointestinal manifestations. We studied 50 migrainous children (mean age 8.63 years). The clinical pattern and the diagnosis of FGIDs were obtained from structured questionnaires. All subjects underwent measurement of total gastric emptying time (TGEt) performed by real-time ultrasonography of the gastric antrum at baseline (T0). In the second part of the study, we evaluated 10 migrainous children (mean age 9.8 years) with associated FGIDs. In these 10 patients, repeated TGEt evaluation together with a detailed symptom history was obtained after 1 (T1) and 2 months (T2) of treatment with flunarizine. Control groups were composed of 10 migrainous children without FGIDs (mean age 9.2 years) and nine sex- and age-matched healthy children. Gastrointestinal disorders were present in 70% of the patients. Migrainous children with FGIDs had significantly (P < 0.01) more prolonged TGEt than subjects without FGIDs. Prior to therapy, all migrainous children with FGIDs had prolongation of TGEt compared with controls (P < 0.05). Patients on flunarizine had a significant decrease in TGEt at both 1 (P < 0.01) and 2 months (P = 0.002) of therapy. The mean frequency of abdominal pain per month was significantly (P < 0.001) reduced at T1 compared with T0. The mean frequency of vomiting per month was significantly decreased at T1 (P < 0.05) and even more so at T2 (P < 0.01). Finally, the mean frequency of headache per month was significantly reduced only at T2 (P < 0.05), whereas the mean duration of headache was significantly decreased at T1 (P < 0.01) with no difference between T1 and T2. Most children with migraine report FGIDs, associated with a delayed gastric emptying. Flunarizine decreases the frequency and duration of migrainous episodes as well as the gastrointestinal symptoms.

Topics: Anticonvulsants; Child; Female; Flunarizine; Gastric Emptying; Gastrointestinal Diseases; Humans; Male; Migraine Disorders; Prevalence; Treatment Outcome; Ultrasonography

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Body Mass Index; C-Peptide; Female; Flunarizine; Humans; Insulin; Leptin; Male; Migraine Disorders; Vasodilator Agents; Weight Gain

This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n=58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P<0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe.

Topics: Adolescent; Adult; Aged; Chi-Square Distribution; Confidence Intervals; Double-Blind Method; Drug Administration Schedule; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Statistics, Nonparametric

We have investigated the prolactin response to bromocriptine (BRC), a D2 dopamine receptor agonist in migrainous women before and after treatment with flunarizine. We evaluated whether this test was predictive of therapeutic efficacy of flunarizine treatment and whether the therapeutic response to flunarizine treatment was related to its effect on dopaminergic system at tuberoinfundibular level. Ten migrainous women underwent a BRC test in the late follicular phase before and after 1 and 3 months of treatment with flunarizine 10 mg at bedtime. Blood samples of prolactin (PRL), growth hormone, follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were taken at basal condition. PRL was also evaluated 1 and 2 h after BRC (2.5 mg) administration. Each patient kept a daily headache diary for 1 month prior to the test and throughout the study. The level of PRL inhibition after BRC administration, observed before flunarizine treatment, was not predictive of the therapeutic response observed after 1 and 3 months of treatment. The effect of flunarizine on PRL level was not related to the therapeutic efficacy of the drug. These data suggest that flunarizine does not attenuate the activity of dopaminergic neurons in migrainous patients, and that the antimigraine effect of flunarizine does not seem related to its action on dopaminergic system at least at tuberoinfundibular level.

Topics: Adult; Analysis of Variance; Bromocriptine; Calcium Channel Blockers; Dopamine Agonists; Female; Flunarizine; Humans; Migraine Disorders; Neurosecretory Systems; Prolactin; Receptors, Dopamine; Treatment Outcome

This multicenter, double-blind, clinical study was designed to compare the efficacy and safety of alpha-dihydroergocryptine and flunarizine in the prophylaxis of migraine without aura. One hundred thirty-five patients fulfilling the diagnostic criteria of the International Headache Society were enrolled at five neurologic centers. The study design included a 1-month pretreatment phase with placebo; a 6-month, double-blind, double-dummy treatment phase with alpha-dihydroergocryptine (10 mg twice daily) or flunarizine (5 mg once daily); a further 3-month follow-up phase without treatment. Efficacy was assessed using the patient's diary. Laboratory tests, vital signs, and adverse events were monitored. Analysis of covariance for repeated measures was performed on the intent-to-treat sample. Both treatments led to a significant reduction in the frequency of migraine, days with headache, and use of relief medication. Overall, 51% of those treated with alpha-dihydroergocryptine and 49% of those treated with flunarizine were responders (50% or greater reduction in attack frequency), the average percentage of reduction being 64% with alpha-dihydroergocryptine and 51% with flunarizine. There was no significant difference between the two groups in terms of incidence of adverse events; dizziness and weight gain were the most frequent observed adverse events with alpha-dihydroergocryptine and flunarizine, respectively. Based on the overall improvement in migraine parameters, alpha-dihydroergocryptine can be recommended for use in migraine prophylaxis.

Topics: Adult; Dihydroergotoxine; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Recurrence; Treatment Outcome

We evaluated whether type of response to the migraine-induction test with a nitroglycerin ointment applied to the frontotemporal head region could predict the efficacy of antimigraine therapy. Forty-two patients with migraine without aura underwent the test before and 2 months after antimigraine therapy. Two and 4 months after treatment withdrawal, most subjects with a negative response to the post-treatment test maintained treatment benefit, whereas benefit was lost in patients with an early onset migraine response.

Topics: Adult; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Nitroglycerin; Propranolol; Time Factors; Treatment Outcome; Vasodilator Agents

This prospective, open multi-centre study on flunarizine focused on the risk/benefit ratio of the use of flunarizine in the prophylaxis of migraine and in the treatment of vertigo, due to disorder of the vestibular system. The assessment of risks focused on the incidence of new events of depression and/or extrapyramidal syndrome during flunarizine treatment. For migraine, flunarizine was compared to propranolol in 686 patients; for vertigo, flunarizine was compared to betahistine in 198 patients. The incidence of depression during follow-up in this study was significantly higher in the flunarizine group than in the propranolol group in the condition of migraine. There were no observations of an extrapyramidal syndrome. There was a suggestion that flunarizine has more benefits than propranolol in the condition of migraine, and that betahistine has more benefit than flunarizine in the condition of vertigo. Differences in dosages could possible explain these differences.

Topics: Adult; Data Collection; Depressive Disorder; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Netherlands; Product Surveillance, Postmarketing; Prospective Studies; Vasodilator Agents; Vertigo

Fourty-five migraine without aura patients underwent a parallel double-blind trial aiming the comparison of the effects of propranolol 60 mg/day to flunarizine 10 mg/day and to propranolol 60 mg/day plus flunarizine 10 mg/day simultaneously. There were 3 groups, each one with 15 patients. After a 20-day-baseline period, each group received one kind of treatment during 120 days. Migraine index on propranolol was 23.4*, on flunarizine 18.7* and on both drugs 14.4*, mean frequency of attacks on propranolol was 1.26**, on flunarizine 1.2** and on both drugs 1.13** (*p < 0.05, **p < 0.01 compared to baseline) and global evaluation was reduced with all forms of treatment. It was not found statistical differences between groups, nevertheless there was a trend in the group using two drugs reaching lower values in migraine index, frequency of attacks and global evaluation. In individuals using flunarizine (alone or associated with propranolol) the therapeutic effect was largely maintained up to 45 days after drug withdrawal.

Topics: 1-Propanol; Adolescent; Adult; Double-Blind Method; Drug Combinations; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders

A comparative post-marketing surveillance study of the safety and efficacy of flunarizine and propranolol in the treatment of migraine was carried out. General practitioners in Belgium and the Netherlands each recruited patients for whom they would prescribe one of the study medications in the normal course of their treatment and recorded all medical events on follow-up forms for up to 8 months. A total of 1601 migraine patients were enrolled; 838 in the flunarizine cohort and 763 in the propranolol cohort. Propranolol was somewhat better than flunarizine in reducing the severity of migraine attacks, although this may have been due to a selection bias. Discontinuations of therapy due to events considered likely to be treatment-related were mostly due to the recognized side effects of the two drugs. As regards the occurrence of depressions, a total of 58 patients had depressive events, 34 in the flunarizine cohort and 24 in the propranolol cohort. Whereas migraine itself appears to be associated with an increased risk of depression, the number of previous migraine treatments was shown to be an additional risk factor for the development of depression in patients receiving flunarizine as was a history of depression. Overall, there was no appreciable difference in the risk/benefit ratio between flunarizine and propranolol.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Belgium; Child; Cohort Studies; Depression; Fatigue; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Netherlands; Propranolol; Prospective Studies; Risk Factors; Safety; Treatment Outcome; Vasodilator Agents; Weight Gain

Various open and controlled studies have confirmed the antimigraine action of flunarizine, while the antimigraine properties of nimodipine are still open to controversy. Moreover, only a few studies include an additional follow-up after discontinuation of migraine prophylaxis with either drug. We carried out a single blind evaluation of the efficacy and tolerance of flunarizine (25 patients) in comparison with nimodipine (25 patients) and the long-term effect after discontinuation of a 6-month treatment. Both medications significantly reduced migraine frequently and severity. Flunarizine was more efficacious than nimodipine in reducing migraine frequency (p < 0.001), pain severity (p < 0.05), migraine index (p < 0.05) and corrected migraine index (p < 0.05). The positive effect lasted 8.4 +/- 4.0 months after discontinuation of flunarizine and 4.9 +/- 3.5 months after nimodipine (p < 0.05). Our results suggest that flunarizine is more effective than nimodipine in the prophylactic treatment of migraine. The positive effect after drug discontinuation lasts longer with flunarizine, compared to nimodipine.

Topics: Adult; Calcium Channel Blockers; Female; Flunarizine; Follow-Up Studies; Humans; Male; Migraine Disorders; Nimodipine; Severity of Illness Index; Single-Blind Method; Time Factors; Treatment Outcome; Vasodilator Agents

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

Topics: Adolescent; Adult; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Nifedipine

Calcium antagonists have been proposed for the prophylactic treatment of migraine because of their putative vasodilating antispasmodic effect and of their action against the cellular consequences of brain hypoxia. Published reports of controlled double-blind studies of calcium antagonists for the prophylactic treatment of migraine are reviewed herein. The effectiveness of verapamil, diltiazem, and nifedipine in this indication cannot be considered as firmly demonstrated, when problems with trial design and the amount of available data are taken into account. Nimodipine failed to demonstrate significant effectiveness in migraine with or without an aura. In contrast, the ability of a diphenylpiperazine, flunarizine, to decrease the incidence of migraine attacks in patients with common or classical migraine has been firmly demonstrated, although there is less evidence of this agent's effectiveness on the duration and severity of attacks. The percentage of patients who respond to flunarizine seems comparable to the percentages of propranolol or pizotifen responders. However, flunarizine is associated with unpleasant (weight gain) or severe (extrapyramidal or depressive symptoms) adverse effects which limit its place to that of a second-line drug. Lastly, the analysis of these studies failed to disclose a correlation between calcium movements across the cell membrane and effectiveness for the prevention of migraine attacks. Flunarizine's effect in migraine probably involves monoamine mechanisms which bear no relation to calcium.

Topics: Adrenergic beta-Antagonists; Clinical Trials as Topic; Diltiazem; Flunarizine; Humans; Migraine Disorders; Nifedipine; Nimodipine; Verapamil

This study was designed to compare flunarizine, a cerebro-specific calcium channel antagonist, and propranolol in the prophylaxis of migraine with or without aura. Following a 1 month single-blind placebo baseline period, 94 patients were equitably randomised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months. Neither treatment affected the severity nor duration of migraines. Overall, 67% of flunarizine patients and 51% of propranolol patients responded positively. Propranolol significantly reduced blood pressure and heart rate; flunarizine had no effect on cardiovascular function. Weight gain was noted with both treatments. Flunarizine is at least as effective as propranolol in the prophylactic treatment of migraine and may have a better safety profile.

Topics: Adolescent; Adult; Aged; Body Weight; Canada; Double-Blind Method; Female; Flunarizine; Hemodynamics; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Single-Blind Method

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.

Topics: Adolescent; Adult; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Regression Analysis

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.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Placebos; Time Factors

The prophylactic effect of flunarizine and metoprolol was studied in a multi-center randomized, double-blind trial of 149 patients with migraine with or without aura. After a 4-week placebo run-in period, patients were randomly allocated to treatment with flunarizine 10 mg daily or metoprolol 200 mg daily for 16 weeks (parallel group design). Both drugs reduced the number of migraine days per month by 37% (95% confidence interval 21-53%) compared with the placebo run-in period. All efficacy parameters were significantly reduced by both drugs and no significant difference was found between the two drugs at any time of the treatment period. However, calculation of the 95% confidence limits showed that each drug may have a superiority of more than 100% on a single main effect parameter. The most common adverse experiences were day-time sedation (both drugs) and weight gain (flunarizine). Depression was the most serious side-effect occurring in 8% on flunarizine and 3% on metoprolol. We conclude that both drugs are effective in the prevention of migraine attacks but a higher number of dropouts occurred on flunarizine because of depression or weight gain.

Topics: Adult; Double-Blind Method; Female; Flunarizine; Humans; Male; Metoprolol; Middle Aged; Migraine Disorders

Following tooth pulp extirpation, some subjects suffer from persistent pain which affects edentate sites in absence of any local pathology. As regards this peculiar pain, called phantom tooth pain (PTP), what is puzzling is the fact there is a low prevalence of PTP in a very large population showing identical conditions of tooth pulp extirpation. The present investigation indicates that PTP mainly affects migraine (M) and cluster headache (CH) sufferers, whereas it does not affect subjects who have a negative personal and family history for idiopathic headache (IH). These results circumscribe the presence of PTP to a specific section of the population. The present results, besides indicating that PTP may be the result of a peculiar neuronal predisposition relating to IH pathogenesis, suggests some practical therapeutic hints. In fact, successful anti- M and anti-CH prophylactic treatment greatly improve PTP syndrome.

Topics: Cluster Headache; Female; Flunarizine; Humans; Lithium; Male; Middle Aged; Migraine Disorders; Pain, Postoperative; Phantom Limb; Pulpectomy; Risk Factors

Flunarizine, a calcium channel blocker is considered useful in migraine prophylaxis. We report the first Indian trial with this drug. Fifteen patients with migraine were studied in a 6 months double-blind, placebo-controlled crossover trial. Flunarizine was superior to placebo in reducing the severity and duration of the individual attacks though there was no statistically significant effect on frequency of migraine attacks. The side effects most frequently caused by flunarizine were weight gain and daytime sleepiness.

Topics: Adult; Drug Evaluation; Female; Flunarizine; Humans; Male; Migraine Disorders; Pain

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.

Topics: Double-Blind Method; Flunarizine; Humans; Migraine Disorders

In this single-blind, parallel group study, the efficacy of verapamil (240 mg/die) vs flunarizine (10 mg/die) for prophylactic treatment was evaluated in 38 patients (8M and 30F, mean age 34.4 years) with common or classic migraine. During the 3 months study, both drugs were found to be effective in reducing the number and intensity of the attacks. Verapamil showed better safety than flunarizine.

Topics: Adolescent; Adult; Drug Evaluation; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Time Factors; Verapamil

Notwithstanding progress in the prophylactic treatment of migraine, the available therapies are often inefficient and unsatisfactory. In this study, 50 patients suffering for at least one year from the classic or common type migraine and treated with calcium-antagonists: Verapamil, Flunarizine, Diltiazem, Nimodipine, as well as placebo, were studied. 34 patients completed the study. All of the calcium-antagonists studied resulted efficacious in the prophylaxis of migraine; however, more attention should be paid to Flunarizine since this substance, in addition to its therapeutic efficacy, also has the advantages of a single daily dose which makes it the drug of choice in the prophylaxis of vasomotor migraine.

Topics: Adolescent; Adult; Diltiazem; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Nimodipine; Placebos; Verapamil

We administer during 6 months in randomised way dihydroergotamine or flunarizine to 50 children affects of classical or common migraine. A significative improvement was estimated in frequency, intensity and duration of their crisis in 87% with dihydroergotamine and 79% with flunarizine, without significative differences from one to other. Dihydroergotamine was specially effective in children with vegetative lability. The secondary effects, 12% with dihydroergotamine and 20% with flunarizine, were trivial and advantageous even, without the necessity of stop the treatment in not any case.

Topics: Age Factors; Child; Child, Preschool; Dihydroergotamine; Dose-Response Relationship, Drug; Flunarizine; Humans; Migraine Disorders; Parents

In a multi-centre, randomized double-blind study, the effect and tolerance of 10 and 20 mg flunarizine i.v. versus placebo was tested on 102 migraineurs with acute migraine attacks with and/or without aura. Thirty-seven patients received 10 mg flunarizine, 32 received 20 mg and 33 received placebo. The groups were comparable. Response to treatment was defined as pain reduction of at least 50% within 60 min on a visual analogue scale after i.v. drug administration. This effect was noted on 59.4% with 20 mg flunarizine, on 24.3% with 10 mg flunarizine and on 30.3% with placebo. The tolerance of flunarizine i.v. was similar to placebo. Blood pressure and pulse rate were not affected by flunarizine. All in all, 20 mg flunarizine i.v. appeared to be a suitable alternative for treatment of acute migraine attacks.

Topics: Acute Disease; Adolescent; Adult; Aged; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

Nimodipine is one of the most discussed calcium antagonists used in cerebrovascular diseases and, recently, in migraine prophylaxis. Its specificity in preventing cerebral arterial constriction has been invoked to explain nimodipine's efficacy in migraine. The discovery of neuronal receptors specific for dihydropyridines, however, favours a mechanism of action for nimodipine that is not exclusively vascular. This is in accordance with a view of migraine pathogenesis which implicates a primary neuronal event as the basis of the vascular changes observed in migraine patients.

Topics: Clinical Trials as Topic; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Nimodipine

The clinical efficacy of flunarizine and propranolol for the prevention of migraine attacks was assessed in 33 children in a double blind study. After a run-in phase of one month, 32 patients started the active medication. A reduction in the number of migraine attacks was observed in 75% of the flunarizine group and in 73.8% of the propranolol group. Propranolol also reduced the severity of attacks. Transient side effects were observed in 3 of 17 of the flunarizine group and in 5 of 15 of the propranolol group. The most frequent side effect was increased fatigue, which required interruption of therapy in 2 patients of the propranolol group.

Topics: Adolescent; Child; Child, Preschool; Double-Blind Method; Female; Flunarizine; Humans; Male; Migraine Disorders; Propranolol; Surveys and Questionnaires

The calcium-entry blocker flunarizine (Sibelium; Janssen) was compared with the beta-adrenoreceptor-blocking agent propranolol in the prophylaxis of migraine. Fifty-eight patients were entered into a double-blind 4-month treatment trial. Patients in whom beta-blockers were contraindicated were excluded from the trial. At the end of the trial 28 patients had received 10 mg flunarizine at night during the study, 29 patients had received 60 mg propranolol 3 times a day and 1 patient was withdrawn. Both groups responded well; and there was a 4-fold drop in frequency of attacks. There was no significant difference between the two groups in terms of patient profile, onset of response to therapy, final response to therapy, incidence of dropout from the trial or incidence of side-effects. Side-effects for flunarizine were weight gain (9 patients) and tiredness (6), and for propranolol sleep disturbances including nightmares (6), tiredness (8), mental changes (e.g. irritability) (3) and weight gain (4). Both flunarizine and propranolol are useful drugs for migraine prophylaxis and can be used effectively as first-line drugs. The low incidence of generally mild side-effects with flunarizine may make it preferable to many of the agents at present in use for migraine prophylaxis.

Topics: Adolescent; Adult; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Randomized Controlled Trials as Topic

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.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Injections, Intravenous; Male; Middle Aged; Migraine Disorders

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.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Multicenter Studies as Topic; Patient Dropouts; Propranolol; Random Allocation

Sixty-four Spanish neurological centers participated in a study designed to evaluate the efficacy and safety of flunarizine in migraine. One thousand four hundred and thirty-five outpatients (367 [25.6%] males and 1,068 [74.4%] females) fulfilling the criteria proposed by the International Headache Society for the diagnosis of migraine entered the study. Patients were treated with 10 mg of single-dose flunarizine (Sibelium) alone at bedtime in open fashion for 6 months. At the end of this treatment period, flunarizine was withdrawn, but the follow-up of the patients continued for another 6 months. The evaluation criteria used were a rating scale (the GES) based on frequency, duration, intensity, and characteristics of the attacks as well as a checklist of possible side-effects. This clinical assessment was recorded in detail in the patients' rating notebooks at the start and at the end of the third, sixth, ninth, and twelfth month of the study. A mean decrease of 66.9% in the GES was obtained at the end of the treatment period, which implies a good or excellent result in the prophylaxis of migraine attacks in 69.5% of the patients. This improvement was practically unchanged at the end of the follow-up period. Side-effects were moderate, the most frequent ones being drowsiness and weight gain. Their incidence decreased after the first months of treatment.

Topics: Adolescent; Adult; Child; Female; Flunarizine; Follow-Up Studies; Humans; Male; Migraine Disorders; Multicenter Studies as Topic

Topics: Administration, Sublingual; Clinical Trials as Topic; Ergotamine; Ergotism; Flunarizine; Humans; Migraine Disorders

Topics: Adult; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Heart Rate; Humans; Male; Metoprolol; Migraine Disorders

Flunarizine (FLU) treatment has proved effective for migraine but there have been reports--though controversial--of depression and/or extrapyramidal signs and symptoms in cases of chronic therapy. It has been suggested that FLU may interfere with the activity of central dopaminergic systems. In this study, prolactin (PRL) secretion was chosen as a parameter for functional exploration of central dopaminergic systems in normal and migraineous women before and after FLU treatment. Five healthy women were given FLU (20 mg) and placebo per os, each for one day. A significance increase of serum PRL levels was found after FLU administration, but not after placebo. Ten women with common migraine underwent TRH stimulation test (200 micrograms i.v.) before and after a 30-day FLU therapy (10 mg per os). Basal PRL levels were not modified by the treatment, but TRH stimulated PRL values were significantly enhanced after a 30-day FLU therapy. These results seem to confirm the hypothesis that FLU interferes with central dopaminergic activity.

Topics: Adult; Depression; Female; Flunarizine; Humans; Migraine Disorders; Prolactin; Thyrotropin-Releasing Hormone

Topics: Acute Disease; Administration, Sublingual; Adolescent; Adult; Aged; Clinical Trials as Topic; Ergotamine; Ergotamines; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders

In the course of a 16 weeks' interval treatment of migraine in connection with two multicenter double-blind studies, flunarizine was compared with propranolol in patients suffering predominantly from "classical migraine". Eighty-seven patients from 12 outpatient departments were admitted to the first study, while 434 patients from 99 medical practices participated in the second study. After each month of treatment, the patients were clinically evaluated, and the number, duration, and severity of attacks were documented. Concerning the frequency and intensity of attacks, additional analgesics consumption and overall evaluation, both drugs proved to be highly effective in the practice as well as in the hospital study. The percentage and severity of side-effects were comparable in the two treatment groups. Summarizing, it may be stated that the studies proved the efficacy of flunarizine to be rather similar to that of propranolol in the prophylactic treatment of migraine.

Topics: Adult; Analgesics; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Time Factors

Flunarizine, 20 mg by slow intravenous injection, was studied in the acute treatment of migraine attacks in a multicentre, double-blind, placebo-controlled study. At the end of the 60 min observation period, 23 of the 31 (74.2%) patients treated with flunarizine reported complete relief, or a pain reduction of more than 50%, vs. 8 of 29 (27.6%) placebo patients (p less than 0.017). Accompanying symptoms also improved significantly better in the flunarizine than in the placebo group. The investigators evaluated the therapy as good or excellent in 77.4% of the flunarizine and in 27.6% of the placebo patients, respectively. Tolerance of the therapy was good and comparable in the two groups. Somnolence was the only flunarizine-related adverse reaction. Blood pressure and heart rate were not affected. Flunarizine i.v. deserves further study in the acute treatment of a migraine attack.

Topics: Adult; Blood Pressure; Double-Blind Method; Female; Flunarizine; Humans; Injections, Intravenous; Male; Middle Aged; Migraine Disorders; Nausea; Placebos

Topics: Adult; Clinical Trials as Topic; Delayed-Action Preparations; Dihydroergotamine; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders

An 8-month, double-blind, placebo-controlled, crossover trial of flunarizine in the prophylaxis of migraine has been performed in 70 children. After 4 weeks of medication-free base-line observation, 35 children (group A) received flunarizine (5 mg/day) and 35 (group B) received placebo over a 12-week period. After a 4-week washout they crossed treatments for another 12 weeks. Sixty-three patients completed the trial. In both groups flunarizine significantly reduced the frequency and average duration of headache attacks. In group A efficacy was maintained after placebo crossover for the last 4 months of the study. Five subjects in group B stopped placebo because of ineffectiveness; two children in group A discontinued flunarizine treatment, one because of excessive daytime sedation and the other because therapy was ineffective. The main side effects were daytime sedation and weight gain. It is concluded that flunarizine is an effective drug for the treatment of childhood migraine. In a study of this length no serious side effects were discovered.

Topics: Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Migraine Disorders; Sleep Stages

Flunarizine is widely used in the prophylaxis of migraine. It is both a calcium blocker and a histamine antagonist at H1-receptors and either of these effects could alter hormonal secretion. The effect of administration of flunarizine to 8 women with common migraine on pituitary secretion has been studied. The dopamine antagonist domperidone (10 mg) and gonadotropin releasing hormone (100 micrograms) were injected iv before and after one month of flunarizine therapy (10 mg orally at bedtime). The basal prolactin level was significantly increased by the drug, and the peak induced by domperidone stimulation was reduced. Basal TSH concentrations were not affected, but the increase after domperidone was blunted. After 90 days of therapy there were no significant differences from the baseline concentration. Neither basal nor gonadotropin releasing hormone-stimulated secretion of FSH and LH were affected by flunarizine. Twelve healthy men were given placebo and flunarizine (10 mg at bedtime) for 5 days in single-blind fashion. Flunarizine caused a significant increase in prolactin and TSH with no effect on basal gonadotropin and thyroid hormone levels. These results can be accounted for by the calcium blocking effect of the drug, although weak interference with dopaminergic transmission is a further possibility explanation.

Topics: Adult; Female; Flunarizine; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Migraine Disorders; Pituitary Gland, Anterior; Pituitary Hormones, Anterior; Prolactin; Thyrotropin

In a double-blind, parallel-group randomised trial of 3 months' duration, the efficacy of cyclandelate 800 mg twice daily in migraine prophylaxis was compared with that of flunarizine 5mg daily in 40 patients. In comparison with placebo and baseline values, both drugs significantly relieved symptoms of migraine as assessed by indices of pain total index, headache index, analgesic consumption and number of migraine days. Patients taking flunarizine experienced side effects such as drowsiness, weight gain and asthenia, while the most common complaint reported with cyclandelate was gastric upset. These results suggest that cyclandelate may be a useful alternative in migraine prophylaxis.

Topics: Adolescent; Adult; Clinical Trials as Topic; Cyclandelate; Double-Blind Method; Female; Flunarizine; Humans; Male; Mandelic Acids; Middle Aged; Migraine Disorders; Random Allocation

30 children between 7 and 17 years suffering from at least 2 attacks/month of common or classical migraine since more than 1 year were studied. After clinical exclusion of symptomatic headache 4 weeks were documented by means of a migraine diary. Prophylaxis with Calcium entry blocker Flunarizine (Sibelium) or Thromboxane A inhibitor Acetylsalicylic acid (ASS) was carried out in a double blind design for 3 months. Medication was given as one dosage in the evening: 2-5 mg/kg KG ASS or 5-10 mg Flunarizine. Documented attack frequency and duration were controlled at monthly physical examinations. Final results showed no differences in significant reduction of attack frequency or symptoms between both different therapeutic principals. 72.4% (ASS 73.3%; Flunarizine 71.4%) of patients were attack-free or had at least a 50% reduction. Migraine frequency of initially 7-8 was reduced to 1-2 attacks/month. Duration remained constant in both groups (1-3 h). Side effects were slight body weight gain or abdominal pain after intake, prophylaxis had not to be interrupted therefore. Longtime prognosis is not yet possible because the time of observation is too short so far.. Both substances are definitely useful and have few side effects in childhood migraine. If the response to one is insufficient the other substance should be tried.

Topics: Adolescent; Aspirin; Child; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Flunarizine; Humans; Male; Migraine Disorders

Topics: Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Epilepsy; Female; Flunarizine; Hemiplegia; Humans; Male; Migraine Disorders

Topics: Adult; Clinical Trials as Topic; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Nimodipine; Pilot Projects

Topics: Administration, Oral; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Ergotamine; Ergotamines; Female; Flunarizine; Humans; Male; Migraine Disorders; Random Allocation

Topics: Adult; Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Pizotyline; Random Allocation; Thiophenes

The results of a double-blind cross-over clinical trial involving 27 patients with classical or common migraine are described to compare the prophylactic effect of the calcium entry blocker flunarizine with that of pizotifen. Duration of the treatment was two months, with an evening single-dose administration of both drugs. For most parameters, there was no definite difference between flunarizine and pizotifen in migraine prophylaxis. It has been demonstrated previously that pizotifen is an effective drug in migraine prophylaxis, and these results suggest that flunarizine is effective, too. Weight gain as a side effect was less frequent and less severe with flunarizine than with pizotifen; other side effects showed the same incidence with both drugs.

Topics: Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Flunarizine; Humans; Migraine Disorders; Pizotyline; Thiophenes; Time Factors

After four weeks of medication-free baseline observation, 29 patients with common migraine randomly received flunarizine (10 mg daily) or placebo for a 16-week period. After four weeks wash-out they crossed treatments for another 16 weeks; 27 patients completed the trial. Compared with placebo, flunarizine significantly reduced the frequency of migraine attacks and the derived headache indices, but the duration and severity of single attacks remained unchanged (Mann-Whitney U-test). The effect of flunarizine increased during the 16-week treatment period and during the last four weeks the number of migraine attacks reduced to 50% compared to the wash-out period. The only side-effect of flunarizine was mild daytime sedation in three patients. It is concluded that flunarizine is a valuable new prophylactic agent for common migraine.

Topics: Adolescent; Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Random Allocation; Time Factors; Vasodilator Agents

In this double-blind study versus placebo, the anti-migraine efficacy of flunarizine 20 mg/per os/day for 14 days, followed by 10 mg/per os/day up to 120 days has been evaluated in 30 patients suffering from common and classical migraine. During the trial the vestibular function (slow phase velocity (SPV) and number of spikes) was also studied. To date 18 patients have completed the study. The results show a significant difference before and after the treatment with flunarizine, while no difference was observed in the placebo group, with regard to headache unit indices. Flunarizine seems to increase SPV max, which is reduced between attacks in migraine patients; the number of spikes does not change significantly.

Topics: Adolescent; Adult; Cinnarizine; Electronystagmography; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders

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.

Topics: Adult; Aged; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Placebos

Pharmacological data and early clinical experience have suggested that the calcium entry blocker flunarizine may be a valuable asset in the prophylaxis of migraine. This was supported by a study in twenty patients with classical migraine who were, after a drug-free running-in phase, orally treated with either placebo or flunarizine (10 mg at night) for three to four months. Flunarizine significantly reduced the frequency, duration and severity of the migraine attacks. A corrected migraine index, based on these three variables, was reduced by 82% in the drug group but increased by 66% in the control patients. Only one patient did not clearly benefit from flunarizine, and the response in another illustrated that flunarizine has to be given for at least four months before its efficacy can be judged in some cases. No side effects occurred.

Topics: Adult; Aged; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Random Allocation

Flunarizine was given in daily doses of 10 mg for periods of two to four months to 176 patients suffering from various types of headache. The symptoms were improved in 82% of the cases treated. No differences emerged among the various types of headache reported by the patients or in relation to the presence or absence of neurological involvement or its type.

Topics: Adolescent; Adult; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Vascular Headaches

In order to assess the effects of flunarizine in long-term prophylaxis of common migraine, 120 subjects (90 female and 30 male) were treated with 10 mg at bedtime and followed-up for two years. The effectiveness of the drug was assessed by investigating the variations of the Headache Index (HI) and of the intake of analgesics. The patients considered responders were those with an at least 60% reduction of the HI compared with the baseline value. To assess side effects, on each follow-up examination the patients were weighed and submitted to the Hamilton Rating Scale for Depression, Toulouse-Pieron test for attention, and arousal test. By the third month of therapy, the average monthly HI had decreased from a baseline value of 16.5 +/- 7.0 to 7.5 +/- 4.2. Also by the third month, 60 subjects had proved responders and 50 non-responders; 10 had dropped out of the study because of side effects or for other reasons. The only statistically significant differences between responders and non-responders were in the baseline HI, which was higher among responders, and in the baseline intake of analgesics, which was higher in non-responders.

Topics: Adolescent; Adult; Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Patient Compliance; Piperazines

Topics: Adult; Blood Pressure; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Female; Flunarizine; Heart Rate; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

The effects of flunarizine administration (10 mg/day, at bed time) were studied in 120 common migraine patients who were followed for 24 months with quarterly controls. Besides headache index (HI) and analgesic use, other variables were monitored, such as arousal (Tolouse Pieron test), mood (Hamilton rating scale for depression), sleep/wake (hrs) and body weight. The study was open-type and after the 6th month control some responder (R) cases (HI reduction greater than or equal to 60%) presenting HI scores less than or equal to 4 could continue the survey off-treatment. The percentage of R cases was 54.5% at the 3rd month, a figure that further increased up to 72% by the 9th month; relapses on treatment were not observed and rebound-headache occurred in 1/4 of R cases let off-treatment. Lower (p less than 0.05) baseline HI values characterized non-responders. Side-effects not requiring withdrawal were drowsiness (42% within the 1st month) and weight gain (mean 7.9 +/- 6.9 kg) in 54% of the cases, while a retarded type depression was the most frequent cause of drop-out from trial (7.5%). The results, while confirming the high prophylactic activity of flunarizine in common migraine, stress the importance of clinical long-term survey of side-effects using antimigraine drugs and suggest the need for further investigations about flunarizine effects on CNS.

Topics: Adolescent; Adult; Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Depression; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Sleep Stages

Topics: Adolescent; Adult; Aged; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Pizotyline

Topics: Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Diltiazem; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Nicotinic Acids; Nifedipine; Nimodipine; Verapamil

Flunarizine, a slow-channel calcium blocker, appeared to be effective in the prophylactic treatment of common and classic migraine in 29 out-patients included in a double-blind clinical trial. After a two-month placebo period, half the patients were treated with flunarizine, 10 mg a day for up to 120 days, half with placebo. Electronystagmographic (ENG) recordings were performed at the end of the common placebo period and after two and four months of treatment, respectively. There was a significant reduction in Headache Unit Index (HUI) and Headache Unit Index Corrected (HUIC) (42% and 40.5% respectively) in the flunarizine-treated group but not in the placebo group. Analgesic intake was reduced and intensity of pain was unchanged in both groups throughout the trial. ENG data were not significantly affected by flunarizine treatment.

Topics: Adult; Cinnarizine; Electronystagmography; Eye Movements; Female; Flunarizine; Humans; Male; Migraine Disorders; Piperazines; Vestibular Function Tests

Flunarizine, a Ca-antagonist with demonstrated antimigraine properties, and indoprofen, an anti-inflammatory non-steroidal agent, were used in the treatment of daily chronic headache. Forty-two migraineurs with interval headache (MIH) were treated with flunarizine in a 6-month open trial, while indoprofen was administered to 23 patients with MIH and 7 with chronic tension headache (CTH) in a 2-month, double-blind, cross-over placebo-controlled study. Flunarizine was found effective in over 65% of the patients, while indoprofen was able to improve headache severity in only 30% of the subjects. In the responder patients, the effectiveness of both drugs is more pronounced in MIH, and seems to be ascribable to the ability of the treatments to reduce number and severity of attacks. A higher incidence of previous affective disturbances is found in non-responsive cases. The analysis of factors converting episodic into chronic headache shows slight but not significant differences between responders and non-responders. An impairment of plasma beta-endorphin levels, in the presence of normal ACTH, cortisol and nociceptive RIII threshold values, characterizes daily chronic headache (DCH) patients. Moreover, indoprofen does not significantly affect these biological and neurophysiological parameters independently of the therapeutic response.

Topics: Adult; Anti-Inflammatory Agents; Calcium Channel Blockers; Cinnarizine; Endorphins; Female; Flunarizine; Headache; Humans; Indoprofen; Male; Migraine Disorders; Pain; Phenylpropionates; Piperazines; Sensory Thresholds

Flunarizine is a 'selective' calcium entry blocker with a similar chemical structure and pharmacological profile to the related compound, cinnarizine. However, in contrast to cinnarizine it has a long plasma half-life and need only be given once a day. The majority of therapeutic trials in the prophylaxis of migraine, occlusive peripheral vascular disease and vertigo of central or peripheral origin have been placebo-controlled, and have shown that the drug produces significantly greater beneficial effects than placebo as evaluated by subjective and objective criteria. A small number of comparative studies have shown flunarizine to be at least as effective as pizotifen in migraine prophylaxis, and in a longer term study as effective as cinnarizine in vertigo of central origin. However, it has not been compared with other drugs which may be useful in these areas, such as methysergide in migraine prophylaxis, some antihistamines or phenothiazines in vertigo, or (understandably at this stage of its evolution) with surgical revascularisation in severe occlusive peripheral vascular disease. In preliminary placebo-controlled studies there was some evidence that flunarizine may improve impaired cognitive function in patients with cerebrovascular disorders, but such findings need further confirmation in additional carefully conducted studies. With a very long half-life, flunarizine may be given once daily; and drowsiness, the main side effect, can be minimised by taking the daily dose in the evening. Thus, it appears that flunarizine will offer a useful alternative in some therapeutic areas that can be difficult to manage with previously available therapy. However, a definitive statement on its relative place in therapy of such conditions must await a few well-controlled comparative studies.

Topics: Adult; Age Factors; Aged; Animals; Anti-Arrhythmia Agents; Anticonvulsants; Blood; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Flunarizine; Histamine H1 Antagonists; Humans; Kinetics; Migraine Disorders; Piperazines; Vascular Diseases; Vasodilator Agents; Vertigo

Seventeen patients with common or classic migraine were prophylactically treated with 10 mg flunarizine daily, whereas 18 patients received a placebo during a 12-week randomized double-blind study. In the gross flunarizine was significantly superior to the placebo. Only 3 patients felt that flunarizine had been useless and the investigator also guessed the medication code correctly in all but these 3 cases. After a 1-month starting period the difference between flunarizine and placebo in reducing the frequency of the migraine attacks became statistically significant in favour of flunarizine. The mean monthly number of attacks was respectively 3.3 and 3.8 before the study and 1.4 and 3.2 during the study. The limited scale of the trial precluded a judgment as to whether one type of migraine would respond better to flunarizine than the other. Side-effects were negligible, weight gain being secondary to the therapeutic effect rather than an untoward consequence of treatment.

Topics: Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Random Allocation

Seventeen patients with common or classical migraine were prophylactically treated with 10 mg flunarizine daily whereas 18 patients received a placebo during a 3-month randomized double-blind study. Globally, flunarizine was significantly superior to the placebo. Only three patients felt that flunarizine had been useless and the investigator also guessed the medication code correctly in all but these three cases. Beyond a 1-month starting period the frequency of the migraine attacks became significantly lower with flunarizine than with the placebo. The mean monthly number of attacks was respectively 3.3 and 3.8 before the study and 1.4 and 3.2 during the study. The limited scale of the trial precludes a judgment as to whether one type of migraine would respond better to flunarizine than the other. Side-effects were negligible, weight gain being considered rather a secondary gain than an untoward consequence of treatment.

Topics: Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Piperazines; Vasodilator Agents

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Migraine Disorders; Piperazines; Pizotyline; Time Factors

In this double-blind, randomized multicenter study involving 75 patients, the calcium-entry blocker flunarizine (10 mg nocte) was compared with pizotifen (2-3 mg per day in three administrations). Duration of treatment was four months. The results suggest that, in the dosage used, flunarizine is at least as effective as pizotifen in both classical and common migraine as regards effect on attack frequency. Flunarizine might tend to more markedly suppress severity of the attack, though. The weight gain seen with both drugs might be slightly less with flunarizine. A practical advantage of flunarizine is its simple dosage schedule (one intake per day).

Topics: Adolescent; Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Pizotyline; Random Allocation; Thiophenes

Topics: Animals; Chickens; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Flunarizine; Hypoxia, Brain; Migraine Disorders; Models, Biological; Piperazines; Placebos; Rodentia

Topics: Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Sex Factors; Time Factors; Vasodilator Agents

Topics: Cinnarizine; Female; Flunarizine; Histamine H1 Antagonists; Humans; Male; Migraine Disorders; Piperazines

Topics: Biomarkers; Brain-Derived Neurotrophic Factor; Calcitonin Gene-Related Peptide; Flunarizine; Headache; Humans; Migraine Disorders; Nerve Growth Factor; Serotonin

Migraine is the third most common disease in the world with an estimated prevalence of 14.7%. The purpose of this study was to identify the characteristic changes in cervical and ocular vestibular evoked myogenic potential (VEMP) and analyse changes in symptoms and VEMP after flunarizine therapy in patients diagnosed with vestibular migraine (VM).. Prospective interventional study was conducted on 31 VM patients. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) were recorded. Flunarizine (10 mg) was given once daily for two consecutive months. Prophylactic therapy was monitored with a monthly follow-up assessment of their symptoms and VEMP was repeated after 2 months.. Headache was the chief complaint (67.7%). Vertigo was spontaneous and mostly moderate in intensity (93%). cVEMP was absent in 1 patient and oVEMP was absent in 3 patients. Post prophylactic treatment with flunarizine, there was significant reduction in the frequency (p = 0.001) and duration (p = 0.001) of headache and frequency (p = 0.001), duration (p = 0.001), and intensity (p = 0.009) of vertigo. cVEMP and oVEMP showed no significant differences (p > 0.05) between pre- and post-treatment recordings.. Treatment with flunarizine helps in considerably reducing the episodes and duration of headache, as well as episodes, duration, and intensity of vertigo.

Topics: Flunarizine; Headache; Humans; Migraine Disorders; Prospective Studies; Vertigo; Vestibular Evoked Myogenic Potentials

Preventive treatment is crucial for patients with chronic migraine (CM). This study explored the association between resting-state cortical oscillations and 3-month treatment outcome in patients with CM. Treatment-naïve patients with CM were recruited with their demographic data, psychosocial data, and headache profiles as well as the healthy controls (HCs). Resting-state cortical activities were recorded using an electroencephalogram and analysed using source-based and electrode-based spectral power method. The regions of interest were the bilateral primary somatosensory (S1) and visual (V1) cortices. After 3-month treatment with flunarizine, patients with CM were categorized into responders and nonresponders. Demographic, clinical, and electroencephalogram data from 72 patients with CM and 50 HCs were analysed. Elevated anxiety, depression, and stress were observed in patients with CM. Theta power in bilateral S1 and alpha and gamma powers in the right S1 increased in patients with CM. Nonresponders (n = 34) exhibited larger alpha powers in bilateral V1 than those in responders (n = 38). Alpha powers also exhibited significant correlations with changes of monthly headache days. Notably, in responders and nonresponders, occipital alpha powers did not differ at baseline and in the third month. In conclusion, patients with CM who were not responsive to preventive treatment were associated with augmented resting-state occipital alpha activity. Moreover, changes in migraine attack frequency were associated with baseline occipital alpha power. However, the prognostic feature of visual alpha oscillation seems to be inherent because it is not altered by flunarizine treatment. These findings may be useful for developing personalised migraine treatment plans.

Topics: Electroencephalography; Flunarizine; Headache; Humans; Migraine Disorders; Treatment Outcome

Migraine is common in primary headaches, and with the development of social economy and the increase in living pressure, the prevalence of migraine has an upward trend.. To observe the clinical effect of flunarizine combined with duloxetine in the treatment of chronic migraine with comorbid depression and anxiety disorders and to provide a reference for clinical treatment.. A total of 118 patients with chronic migraine complicated with depression and anxiety disorder admitted to our hospital from June 2018 to August 2020 were selected and divided into two groups according to treatment methods, 59 cases in each group. The control group was treated with flunarizine combined with loxoprofen sodium, and the observation group was treated with flunarizine combined with duloxetine. The changes of electroneurophysiological indexes, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high sensitivity-C reactive protein (hs-CRP), Hamilton depression scale (HAMD) score, and Hamilton anxiety scale (HAMA) score before and after treatment in the two groups were recorded, and the total effective rate of clinical treatment in the two groups was counted.. After treatment, TNF-α, IL-6, and hs-CRP in the two groups decreased gradually (p < .05). Further comparison between groups showed that TNF-α, IL-6, and hs-CRP in the observation group were lower than those in the control group (p < .05). After treatment, the HAMD score and the HAMA score of the two groups decreased gradually (p < .05). Further comparison between the two groups showed that HAMD score and HAMA score of the observation group were lower than those of the control group (p < .05).. Flunarizine combined with duloxetine in the treatment of chronic migraine with depression and anxiety disorder can effectively improve neuroelectrophysiological indexes, reduce inflammation, and reduce depression and anxiety.

Topics: Anxiety; Anxiety Disorders; C-Reactive Protein; Comorbidity; Depression; Duloxetine Hydrochloride; Flunarizine; Humans; Interleukin-6; Migraine Disorders; Tumor Necrosis Factor-alpha

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Flunarizine; Headache; Humans; Migraine Disorders; Taiwan; Topiramate

Topics: Anxiety; Flunarizine; Humans; Migraine Disorders; Topiramate; Vertigo

Familial hemiplegic migraine (FHM) is a rare, autosomal dominant migraine with aura. CACNA1A encodes the α1A subunit of P/Q-type voltage-gated calcium channels, and its mutations have been associated with a wide spectrum of episodic and chronic neurological disorders, including FHM type 1 (FHM1).. A Chinese girl and some of her relatives who presented with hemiplegia with or without migraine were found to carry a novel heterozygous missense variant, I1379F, in CACNA1A by whole-exome sequencing. The variant consegregated with the disease and was predicted to be pathogenic.. The patient was diagnosed with FHM1 clinically and genetically.. Prophylactic therapy with flunarizine 5 mg daily was prescribed to the patient.. Therapy with flunarizine was terminated after a few weeks. The intensity of the attacks was the same as before.. This case indicates that FHM should be considered when a patient manifests with episodic hemiplegia without migraine. In addition, genetic testing is an indispensable method to identify atypical attacks of hemiplegic migraine.

Topics: Calcium Channels; Cerebellar Ataxia; Female; Flunarizine; Humans; Migraine Disorders; Migraine with Aura; Pedigree

Activation of peripheral and/or central trigeminovascular pain pathways are implicated in the pathogenesis of migraine. Small fibers mediate pain, thermal sensation, and autonomic functions. Axon flare response is correlated with local C-fiber activation and calcitonin gene-related peptide release. Laser speckle contrast analysis (LASCA) detects very subtle microcirculatory changes that are not visible to the naked eye.. Axon flare response was elicited by 0.01 mL intradermal (i.d.) histamine introduced to the left forehead, trigeminal nerve ophthalmic branch (V1) skin area. Skin microvascular blood flow data were recorded using a LASCA real-time microcirculation imaging system. In the healthy control, prick stimulus slightly elevated focal skin microcirculation only at the stimulated focal area. However, in our patient with chronic migraine, the unilateral prick stimulation transiently (over 10 to 12 seconds) increased ipsilateral skin microcirculation at all 3 branches of the trigeminal nerve, with a slight expansion across the midline. Left V1 stimulation by i.d. histamine induced not only prominent but also long-lasting (10 to 15 minutes of recording time) axon flare response at the ipsilateral V1, V2, and V3 areas, with an expansion to the contralateral V1 area and without any report of allodynia or hyperalgesia. The treatment decreased axon flare characteristics probably by inhibiting neurogenic inflammation.. The clinical characteristics and individual response to treatment vary widely across patients with pain. Here, we demonstrated the presence of transient spread of increased microcirculation at the ipsilateral trigeminal nerve, and also across the midline after prick stimulus, whereas a more prominent, widespread, and long-lasting histamine-induced axon flare response occurred in a rare subclass of patient who had chronic migraine with autonomic symptoms. The modulatory effect of the pharmacological intervention has also been objectively quantified by LASCA.

Topics: Adult; Chronic Disease; Female; Flunarizine; Histamine; Histamine H1 Antagonists; Humans; Hyperalgesia; Microcirculation; Migraine Disorders; Perfusion Imaging; Thermography; Trigeminal Nerve

Topics: Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Migraine Disorders; Piperazines; Terminology as Topic

Vestibular migraine (VM) consists of recurrent episodes of vestibular symptoms that are accompanied by migraine in at least 50% of the episodes. The criteria of the Bárány Society include two diagnostic categories: "actual" vestibular migraine and probable vestibular migraine. There is a wide range of drugs that can be prescribed for the prophylactic treatment of VM, but recommendations for the selection of the most appropriate drug are currently lacking.. To measure the extent to which the prophylactic treatment of VM reduces vestibular symptoms, headache and the number of crises depending on the diagnostic category of the Bárány Society and the drug used for prophylaxis.. This is a multicenter prospective study. Patients with VM who presented to any of the participating centers and who subsequently met the VM criteria were prescribed one of the following types of prophylaxis: acetazolamide, amitriptyline, flunarizine, propranolol or topiramate. Patients were called back for a follow-up visit 5 weeks later. This allowed the intensity of vestibular symptoms, headache and the number of crises before and during treatment to be compared.. 31 Patients met the inclusion criteria. During the treatment, all the measured variables decreased significantly. In a visual analogue scale, the intensity of vestibular symptoms decreased by 45.8 points, the intensity of headache decreased by 47.8 points and patients suffered from 15.6 less monthly crises compared to the period before the treatment. No significant between-group differences were found when patients were divided based on their diagnostic category or the choice of prophylaxis prescribed to them.. The treatment of VM produces a reduction of symptoms and crises with no significant differences based on patients' diagnostic categories or the choice of prophylaxis prescribed to them.

Topics: Acetazolamide; Amitriptyline; Analgesics; Central Nervous System Agents; Flunarizine; Humans; Migraine Disorders; Propranolol; Prospective Studies; Topiramate; Vertigo; Vestibular Diseases

This experiment aimed to explore the curative effect of Tuling Wendan Decoction combined with flunarizine on migraine patients and the intervention effect on serum cyclooxygenase-2 (COX-2), endothelin-1 (ET-1), nitric oxide(NO) levels. For this purpose, from January 2019 to January 2020, 96 patients with migraine in our hospital were selected as the research object. Using a simple randomization method, patients who meet the criteria were assigned 1:1, and each patient was assigned a random number, of which the number 1 to 48 were the observation group, and the number 49 to 96 were the control group. The control group was treated with flunarizine, and the observation group was treated with Tuling Wendan Decoction combined with flunarizine. Comparing the efficacy, incidence of adverse reactions, the incidence of headache, cerebral blood flow rate [basal artery (BA), vertebral artery (VA), middle cerebral artery (MCA)], vascular endothelial function (serum COX-2, ET-1, NO levels), neurological function [5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), calcitonin gene-related peptide (CGRP)] before treatment, 4 weeks and 8 weeks after treatment between the two groups. The results for efficacy showed that after 8 weeks of treatment, the total effective rate of the observation group (93.75%) was higher than that of the control group (77.08%, P<0.05). In regards to the situation of headache attack, the number of headache attacks, duration, pain degree and accompanying symptom scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group (P<0.05). Results of cerebral blood flow velocity showed that the blood flow velocity of BA, VA, MCA in the observation group was lower than that in the control group after 4 and 8 weeks of treatment (P<0.05). Vascular endothelial function results indicated that the serum COX-2 and ET-1 levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum NO levels were higher than that of the control group (P<0.05). The serum BDNF and CGRP levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum 5-HT levels were higher than the control group (P<0.05). The incidence of adverse reactions between the two groups was not statistically significant (P>0.05). It was concluded that Tuling Wendan Decoction combined with

Topics: Adult; Cerebrovascular Circulation; Cyclooxygenase 2; Drugs, Chinese Herbal; Endothelin-1; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Nitric Oxide; Young Adult

Gap junctions (GJs), which consist of proteins called connexins, are intercellular channels that allow the passage of ions, second messengers, and small molecules. GJs and connexins are considered as emerging therapeutic targets for various diseases. Previously, we screened numerous compounds using our recently developed iodide yellow fluorescent protein gap junctional intercellular communication (I-YFP GJIC) assay and found that flunarizine (FNZ), used for migraine prophylaxis and as an add-on therapy for epilepsy, inhibits GJIC in LN215 human glioma cells. In this study, we confirmed that FNZ inhibits GJIC using the I-YFP GJIC assay. We demonstrated that FNZ inhibits GJ activities via a mechanism that is independent of calcium channels and dopaminergic D2, histaminergic H1, or 5-HT receptors. In addition, we showed that FNZ significantly increases connexin 43 (Cx43) phosphorylation on the cell surface, but does not alter the total amount of Cx43. The beneficial effects of FNZ on migraines and epilepsy might be related to GJ inhibition.

Topics: Biological Transport; Cell Communication; Cell Line, Tumor; Connexin 43; Connexins; Flunarizine; Gap Junctions; Glioma; Humans; Migraine Disorders; Phosphorylation

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Child, Preschool; Electroencephalography; Female; Flunarizine; Humans; Migraine Disorders; Paresis; Sturge-Weber Syndrome; Vasodilator Agents

For over 20 years, as a group we have been using flunarizine in primary headache disorders. Flunarizine is widely used in Europe, but not licensed in the UK. In September 2014, the National Institute for Clinical Excellence published supportive guidelines for flunarizine use in migraine, based on randomized controlled evidence that it is as effective as propranolol and topiramate in adults.. We reviewed a cohort of adult patients (n = 200) treated with flunarizine from our practice. The clinical information of these patients, i.e. diagnosis, dose, efficacy, side effects and duration of treatment, was collected.. The most common indication for flunarizine use was chronic migraine, followed by migraine with aura, sporadic hemiplegic migraine, familial hemiplegic migraine and new daily persistent headache with migrainous features. Flunarizine was generally effective, with only 24% (n = 47) of patients reporting no clinical effect. The most common dose used was 10 mg per day. Duration of treatment information was available for 39% (n = 78) of patients. Of these patients, 64% (n = 50) continued treatment for more than 1 year. Doses up to 15 mg were generally well tolerated, with only 10.5% (n = 21) of patients stopping treatment due to adverse effects. The most common adverse events were tiredness, mood change and weight gain.. The data provide supportive evidence from tertiary headache practice in the UK for the use of flunarizine in migraine. The data encourages development of future guidance regarding flunarizine use in headache centres in countries where its use is not routine.

Topics: Adolescent; Adult; Aged; Female; Flunarizine; Headache Disorders; Humans; Male; Middle Aged; Migraine Disorders; Treatment Outcome; United Kingdom; Young Adult

Serotonin syndrome (SS) is an iatrogenic, drug-induced syndrome caused by serotoninergic agent. Various serotonergic drugs are used in different headache disorders. Therefore, a possibility of developing SS exists in patients with headache. Herein, we are reporting two patients with headache disorders who developed SS.Case 1: a 49-year-old man had a 6-year history of episodic cluster headache (CH). However, he had never been diagnosed with CH before reporting to us. He had been receiving amitriptyline, tramadol/acetaminophen combination and flunarizine. Lithium was started for CH. He developed features consistent with SS. The patient responded to cyprohepatdine.Case 2: a 36-year-old chronic migraineur was on amitriptyline. Addition of sodium valproate led to the development of new features that fulfilled the criteria of SS. The patient responded to cyprohepatdine.As SS may be fatal, there is a need to increase awareness about SS in physicians treating patients with headache.

Topics: Acetaminophen; Adult; Amitriptyline; Analgesics; Cluster Headache; Drug Therapy, Combination; Flunarizine; Humans; Lithium; Male; Middle Aged; Migraine Disorders; Serotonin Agents; Serotonin Syndrome; Tramadol; Valproic Acid

Topics: Adolescent; Adrenergic beta-Antagonists; Age Factors; Analgesics; Behavior Therapy; Child; Flunarizine; Headache; Health Behavior; Humans; Ibuprofen; Long-Term Care; Magnesium; Migraine Disorders; Sumatriptan

To assess the prevalence of vestibular migraine (VM) in patients consulting to an otolaryngology clinic, the neuro-otological associated symptoms, and the effect of prophylactic antimigrainous medication on VM symptom improvement.. Retrospective chart review.. Tertiary referral otolaryngology clinic.. We used the diagnostic criteria from the Bárány Society and the International Headache Society to allocate patients to a subgroup: VM, possible VM, and atypical VM.. The prevalence of VM, percentages of associated neurotological symptoms, and percentages of effectiveness of prophylactic medication.. Sixty-five (16%) patients were selected from the total patient population (n = 407) from which 4.2% were assigned to the definite VM group, 5.7% to the probable VM group, and 6.1% to the atypical VM group. We found a significantly different distribution between the groups for photophobia (p = 0.035), ear pressure (p = 0.023), and scotoma (p = 0.015). Thirty patients were administered with flunarizine and 68% responded with an improvement in VM symptoms (p < 0.001). For propranolol, 31 patients were treated and there was an improvement of symptoms in 73% (p < 0.001). Remarkable was the fact that these percentages were not significantly different between the subgroups.. VM is a common disorder presenting in a dizziness clinic, and detailed history taking is important to assess VM-associated symptoms and thus to prevent underdiagnosis. The latter is very important because our study shows that the majority of patients, regardless of VM subtype, can benefit from a prophylactic treatment, but further prospective studies are necessary.

Topics: Adrenergic beta-Antagonists; Adult; Calcium Channel Blockers; Dizziness; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Otolaryngology; Photophobia; Prevalence; Propranolol; Prospective Studies; Retrospective Studies; Vertigo; Vestibule, Labyrinth

There is a need for an objective assessment scoring system to evaluate the effectiveness of prophylactic drugs in paediatric migraine, and the aim of this study was to evaluate the Paediatric Migraine Disability Assessment Score (PedMIDAS).. We recruited 88 children aged between 6 and 17 years of age with migraine. The 53 children in the treatment group were divided into three groups according to the prophylactic drug they received topiramate, flunarizine and propranolol and assessed using PedMIDAS before the start of treatment and 3 and 6 months after treatment. The 35 patients in the control group did not receive prophylactic treatment and were assessed with PedMIDAS on three occasions, 3 months apart.. Topiramate, propranolol and flunarizine treatments significantly decreased PedMIDASs and were shown to be effective in improving the patients' quality of life. Topiramate and propranolol were more effective than flunarizine. The number of days on analgesic treatment significantly decreased in the patients who had received topiramate and propranolol treatments (p < 0.05), but remained unchanged in the flunarizine prophylaxis group (p > 0.05).. The PedMIDAS scoring system is useful in evaluating the efficacy of prophylactic therapy in paediatric migraine. Topiramate and propranolol lowered the PedMIDASs better than flunarizine.

Topics: Adolescent; Child; Disability Evaluation; Flunarizine; Fructose; Humans; Migraine Disorders; Propranolol; Topiramate; Treatment Outcome

To compare the adherence between monotherapy and politherapy in prophylactic migraine treatment.. Five hundred consecutive patients with migraine from a tertiary center were retrospectively studied as to the number of preventive medications prescribed during the first visit. Adherence, defined as returning for the next consultation after 4 to 6 weeks and following the prescribed regimens, were also evaluated and compared between patients.. 71.8% were women, and 6% of the patients did not receive any preventive medication, 11.4% received one drug, 22.2% two drugs, 41.4% three drugs, and 19% four drugs for the prevention of migraine. The overall adherence was 79.6%. Respectively, 73.7, 71.8, 82.6 and 86.3% of those who received the prescription of one, two, three and four drugs returned, complying with the treatment.. There is no difference in adherence to monotherapy or politherapy (one to four drugs) for the prophylaxis of migraine.

Topics: Adolescent; Adrenergic beta-1 Receptor Antagonists; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Brazil; Child; Child, Preschool; Drug Therapy, Combination; Female; Flunarizine; Humans; Male; Medication Adherence; Middle Aged; Migraine Disorders; Muscle Relaxants, Central; Prescription Drugs; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult

Intermittent fever has been occasionally related to migraine, either as a migraine equivalent or as a migraine accompaniment. We present a case of recurrent increase in body temperature consistently associated with migraine headaches.. A 15-year-old girl reported a 3-year lasting history of migraine without aura, with a feeling of warmth occurring in each episode. Ancillary tests did not show any evidence of secondary headaches or any systemic disease. A 2-month headache diary was obtained, with daily records of headache intensity (0, no headache; 1, mild pain; 2, moderate pain; 3, severe pain) and simultaneous measurements of axillary temperature. Both parameters were registered in the evening, at 6:00 pm every day. The distribution of headache intensity and body temperature as well as the relationship between both variables over time were analyzed with nonparametric tests.. The number of days without pain was 28 (45.2%); a mild headache was present on 13 days (21%), a moderate headache on 15 days (24.2%), and a severe headache on 6 days (9.7%). Headache days were associated with higher body temperature than headache-free days (median values: 37.3°C vs 36.6°C; Mann-Whitney U-test, P < 0.001). Moreover, a positive correlation was found between headache intensity and body temperature (Spearman's rho coefficient: 0.83, P < 0.001).. Recurrent increase in body temperature may be another manifestation of the complex clinical spectrum of migraine. This symptom is probably related to hypothalamic involvement.

Topics: Adolescent; Body Temperature; Female; Flunarizine; Humans; Hypothalamus; Medical Records; Migraine Disorders; Neurologic Examination; Pain Measurement; Vasodilator Agents

The purpose of this study was to compare the efficacy and tolerability of topiramate and flunarizine for the prophylaxis of pediatric migraines. A retrospective medical-record review of patients who underwent prophylaxis after receiving a diagnosis of migraine with aura and without aura was performed. Only patients who completed at least 3 months of treatment were included in the analysis. Response to treatment was assessed as the total number of headache days/month. Patients with more than 50% reduction in headache days/month were classified as responders. Responder rate, retention rate, and adverse-event rates were also calculated from all patients who started on the prophylaxis. Further analyses were performed using different patient groups with a cut-off age of 12 years. The responder rate was 80% (89/111 patients) for flunarizine and 81% (122/150 patients) for topiramate, based on a comparison among 261 patients. The retention rate was 67% for flunarizine and 63% for topiramate and the adverse-event rate was 6% for flunarizine and 10% for topiramate. The responder rate, the retention rate, and the adverse-event rate were not significantly different between flunarizine and topiramate. These findings were concordant between the preadolescent (6-12 years old) and adolescent (13-18 years old) groups. The efficacy and tolerability of topiramate were not inferior to those of flunarizine for the prophylaxis of pediatric migraines. These findings were observed in preadolescent and adolescent patients.

Topics: Analgesics; Child; Female; Flunarizine; Fructose; Humans; Male; Migraine Disorders; Retrospective Studies; Topiramate; Treatment Outcome

Topics: Child, Preschool; Flunarizine; Humans; Male; Migraine Disorders

INTRODUCTION. Flunarizine, with level of evidence A, and nadolol, with evidence level C, would be indicated as preventive treatment of migraine. Yet, no previous studies have been conducted to compare the effectiveness of the two drugs. AIM. To compare the effectiveness parameters in independent groups of patients treated preventively with one of the pharmaceuticals from the study, the same protocol being applied in both cases. PATIENTS AND METHODS. The subjects selected for the study were patients with episodic migraine (according to 2004 International Headache Society criteria) who had undergone preventive treatment for the first time, with flunarizine (5 mg/day) or nadolol (20-40 mg/day). The main effectiveness variables (reduction in the number of seizures at four months of treatment and responder rates) were analysed. RESULTS. The study included 227 patients who intended to receive treatment: 155 with flunarizine (80.5% females; mean age: 38.3 ± 12.1 years) and 72 with nadolol (63.8% females; mean age: 37.1 ± 12.0 years). The mean number of seizures prior to treatment was 6.09 ± 2.6 in the flunarizine group and 5.1 ± 1.7 in the nadolol group (p = 0.0079); at four months of treatment it was 2.61 ± 2.4 in the flunarizine group and 2.77 ± 2.4 in the nadolol group (p = NS). Percentage of reduction of migraines: 55.2% with flunarizine and 50.4% with nadolol (p = NS). The responder rate was 69% with flunarizine and 67% with nadolol (p = NS). The excellent response rate (reduction in the number of seizures by 75% or more) was 52.2% with flunarizine and 36.1% with nadolol (p = 0.0077). Percentage of adverse side effects: 48.3% with flunarizine and 25% with nadolol (p = 0.0009). The satisfaction rate was similar in both groups, 68%. CONCLUSIONS. Both flunarizine and nadolol proved to be effective in the preventive treatment of episodic migraine. Flunarizine is used more often in our milieu and was less well tolerated.

Topics: Adrenergic beta-Antagonists; Adult; Calcium Channel Blockers; Female; Flunarizine; Humans; Male; Migraine Disorders; Nadolol

Although flunarizine (FLN) has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. It has been hypothesized that migraine is a channelopathy, and abnormal activities of voltage-gated Na(+) and Ca(2+) channels might represent a potential mechanism of cortical hyperexcitability predisposing to migraine. The aim of the present study was to investigate the effects of FLN on Na(+) and Ca(2+) channels of cultured rat cortical neurons. Sodium currents (I(Na)) and calcium currents (I(Ca)) in cultured rat cortical neurons were monitored using whole-cell patch-clamp recordings. Both I(Na) and I(Ca) were blocked by FLN in a concentration-dependent manner with IC(50) values of 0.94μM and 1.77μM, respectively. The blockade of I(Na) was more powerful at more depolarizing holding potentials. The steady-state inactivation curve of I(Na) was shifted towards more hyperpolarizing potentials by FLN. FLN significantly delayed the recovery from fast inactivation of I(Na). Furthermore, the action of FLN in blocking I(Na) was enhanced at higher rates of channel activation. Blockades of these currents might help explain the mechanism underlying the preventive effect of FLN on migraine attacks.

Topics: Animals; Calcium Channel Blockers; Cells, Cultured; Cerebral Cortex; Flunarizine; Ion Channel Gating; Membrane Potentials; Migraine Disorders; Neurons; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Rats; Sodium Channels

Topics: Animals; Cortical Spreading Depression; Flunarizine; Hypoxia, Brain; Male; Migraine Disorders; Mitochondrial Diseases

A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria. SD rats, which were divided into seven groups, received treatment as follows: no intervention (control Group I); 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O(2) inhalation before NaCl injections (Group V); 14% O(2) inhalation followed by KCl injections (Group VI); 14% O(2) inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII). Following treatment, brains were removed for the analysis of mitochondria transmembrane potential (MMP) and oxidative respiratory function after recording the number, amplitude and duration of CSD. The duration of CSD was significantly longer in Group VI than that in Group III. The number and duration of CSD in Group VII was significantly lower than that in Group VI. MMP in Group VI was significantly lower than that in Group III, and MMP in Group VII was significantly higher than that in Group VI. State 4 respiration in Group VI was significantly higher than that in Group III, and state 3 respiration in Group VII was significantly higher than that in Group VI. Respiration control of rate in Group VII was also significantly higher than that in Group VI. Thus, we concluded that aggravated cerebral mitochondria injury might be attributed to CSD under hypoxic conditions. Flunarizine can alleviate such cerebral mitochondria injury under both normoxic and hypoxic conditions.

Topics: Animals; Cortical Spreading Depression; Disease Models, Animal; Flunarizine; Hypoxia, Brain; Male; Migraine Disorders; Mitochondrial Diseases; Rats; Rats, Sprague-Dawley

The drop-out rate among patients receiving preventive treatment for migraine is higher than 30%. This situation is not very widely known and the risk factors that lead patients to drop out from treatment have yet to be identified.. To evaluate some of the factors that can predispose patients to drop out of preventive treatment.. We conducted a prospective study of patients suffering from migraine who required preventive treatment for the first time with one of what are considered the top three first-choice drugs, i.e. a beta-blocker (nadolol), a neuromodulator (topiramate) or a calcium antagonist (flunarizine). Two groups were established according to whether patients dropped out of treatment or not. Different demographic and clinical variables were analysed and compared in the two groups.. Of 800 patients with migraine who required preventive treatment for the first time, the drop-out rate was 19.7%. In the drop-out group, the variables 'age', 'number of seizures', 'number of seizures prior to preventive treatment' and 'side effects' showed significant differences with those from the group of patients who did not drop out of preventive treatment.. The drug used as preventive treatment, the side effects, a younger age and a lower number of seizures before starting the preventive treatment favoured higher drop-out rates. Whether the migraine was episodic or chronic, the presence of medication abuse and the drugs used to treat the seizures were not related with dropping out of preventive treatment.

Topics: Adrenergic beta-Antagonists; Adult; Anticonvulsants; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nadolol; Neuroprotective Agents; Patient Dropouts; Patient Satisfaction; Prospective Studies; Risk Factors; Topiramate; Treatment Outcome; Young Adult

Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine.. Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as <50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed.. Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients.. Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations.

Topics: Adrenergic beta-Antagonists; Adult; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Atenolol; Calcium Channel Blockers; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Nortriptyline; Pilot Projects; Quetiapine Fumarate; Treatment Outcome; Young Adult

To assess the clinical characteristics of patients with migraine.. The medical records of 76 patients diagnosed with migraine were reviewed using the ICHD-II 2004 diagnosis criteria. The patients were classified into three age groups: 3-6 yr olds (group I), 7-12 yr olds (group II), and 13-17 yr olds (group III).. Migraine was the most common cause of headache in the patients of present pediatric neurology outpatient clinic (57.1%, 76/133). The mean age of patients was 11.08 ± 3.27 (3.25-17) yrs. The number of girls as the age increased (groups II and III). The mean headache attacks rate was 2.5 ± 1.5 per wk, which resulted in worsening of school performance (n = 26, 34.2%). In the majority of patients (n = 54, 71.1%), there was a family history of migraine or headache in the close relatives. Prophylaxis was found effective for all given medications (flunarizine: 46/54, propranolol: 19/21, topiramate: 10/10, sodium valproate: 1/1).. These findings indicate that: (a) migraine is the most frequent cause of headache in pediatric patients, (b) it has negative effects on school performance and daily activities, (c) the family history is important for making the diagnosis and (d) prophylaxis is significantly effective.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Flunarizine; Fructose; Humans; Male; Migraine Disorders; Prevalence; Propranolol; Risk Factors; Topiramate; Turkey; Valproic Acid; Vasodilator Agents

The study objective was to evaluate levels of the cytokines tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 and of leptin, and then to determine the relationship between these levels and clinical responses in children with migraine after prophylactic therapy with one of four drugs. In all, 77 children who needed prophylactic drugs were treated with cyproheptadine, amitriptyline, propranolol, or flunarizine. Serum levels of the cytokines and leptin were measured before and 4 months after the treatment. Results were compared by drug for headache frequency, severity, and duration, the PedMIDAS score, and levels of each cytokine and of leptin. Each of the four drugs not only decreased the frequency and duration but also the severity of headache, and the PedMIDAS score. None of the drugs was found to be superior to others in terms of reduction in cytokine levels (P > 0.05). Both cyproheptadine and flunarizine (but not amitriptyline and propranolol) caused an increase in leptin levels (P < 0.05). These data suggest that cytokine levels are related to clinical responses, and might help in objective evaluation of clinical response in migraine. To our knowledge, the present study is the first trial to compare the effects of prophylactic drugs, cytokine levels, and leptin levels in children with migraine.

Topics: Adolescent; Amitriptyline; Central Nervous System Agents; Child; Cyproheptadine; Cytokines; Female; Flunarizine; Humans; Interleukin-1beta; Interleukin-6; Leptin; Male; Migraine Disorders; Propranolol; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Ophthalmoplegic migraine (OM) is a childhood disorder of uncertain etiology manifesting recurrent unilateral headache associated with a transitory oculomotor (usually IIIrd nerve) palsy. Recent publications emphasize the finding on MRI of contrast enhancement in the IIIrd nerve suggesting that OM may be a recurrent inflammatory neuropathy. We report the case of a 7-year-old boy with typical symptoms of this disorder. Angio MR and Angio CT revealed the presence of an infundibular dilatation of a perforating branch of the posterior cerebral artery adjacent to the symptomatic IIIrd nerve. We speculate that this and perhaps other cases of OM may have a different pathophysiology related to compression of the IIIrd nerve by an adjacent vascular structure that could activate the trigeminovascular system and produce migrainous pain.

Topics: Age of Onset; Anti-Inflammatory Agents; Cerebral Arterial Diseases; Child; Child, Preschool; Dilatation, Pathologic; Flunarizine; Humans; Infant; Magnetic Resonance Imaging; Male; Migraine Disorders; Oculomotor Nerve Diseases; Ophthalmoplegia; Prednisone; Radiography; Vasodilator Agents

Psychiatric disorders, notably mood and anxiety disorders, are frequently associated with migraine and chronic daily headaches. The obsessive-compulsive disorder (OCD) is included in the spectrum of anxiety disorders and may be a comorbid condition in headache patients. However, little information has been reported in the literature about this association. This is an important issue as OCD may contribute to the development or maintenance of treatment-resistant chronic headaches. In this paper, we describe a young female patient with refractory chronic migraine and OCD. Considerations on diagnosis, management and treatment of these comorbid conditions are presented.

Topics: Adolescent; Female; Flunarizine; Humans; Migraine Disorders; Obsessive-Compulsive Disorder; Vasodilator Agents

Migraine is a prevalent neurological disorder. Although prevention is the mainstream treatment, some patients are refractory to standard therapies.. To evaluate the use of quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination atenolol + nortriptyline + flunarizine.. Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II) and headache attacks on less than 15 days per month not overusing symptomatic medications were studied. The main inclusion criterion was the lack of response (<50% reduction in attack frequency) after ten weeks to the combination of atenolol (60 mg/day) + nortriptyline (25 mg/day) + flunarizine (3 mg/day). The patients started on QTP as the sole treatment in a single daily dose of 25 mg, titrated to 75 mg. After ten weeks, headache frequency, consumption of rescue medications and adverse events were analyzed.. Twenty nine patients completed the study. Among completers, 22 (75.9%; 64.7% of the intention-to-treat population) presented >50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 and the average consumption of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by 9 (31%) patients.. Although limited by the open design, this study provides a pilot data to support the use of quetiapine in preventive treatment of refractory migraine.

Topics: Adult; Antipsychotic Agents; Atenolol; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Nortriptyline; Pilot Projects; Prospective Studies; Quetiapine Fumarate; Treatment Outcome; Young Adult

Topics: Adult; Aggression; Akathisia, Drug-Induced; Anticonvulsants; Bipolar Disorder; Brain; Dose-Response Relationship, Drug; Female; Flunarizine; Fructose; Humans; Migraine Disorders; Mood Disorders; Topiramate; Withholding Treatment

Topics: Adult; Basilar Artery; Cerebrovascular Circulation; Female; Flunarizine; Humans; Indomethacin; Intracranial Aneurysm; Magnetic Resonance Angiography; Migraine Disorders; Posterior Cerebral Artery; Treatment Outcome; Ultrasonography, Doppler, Transcranial; Vasospasm, Intracranial; Vertebrobasilar Insufficiency

(1) Migraines are characterized by recurrent headaches generally lasting between 4 and 72 hours and disappearing without complication. They can be incapacitating, owing to their frequency and/or intensity. (2) Many drugs have been used to prevent migraines. One of the most common outcome measures used in clinical trials is the proportion of responder patients, defined as those in whom the monthly frequency of migraines is at least halved. On average, about one-third of patients respond to placebo in clinical trials. (3) Propranolol is the betablocker with the best-documented efficacy: in absolute terms the response rate is about 30% higher than with placebo. The adverse effects of betablockers are mainly cardiovascular and neuropsychological. (4) Valproic acid, an anticonvulsant, is about as effective as propranolol, and its adverse effects are generally acceptable. (5) Amitriptyline is the antidepressant with the best-documented preventive effects, with a response rate about 20% higher than placebo. Its principal adverse effects are due to its atropinic action. Amitriptyline can also have a sedative effect. (6) Flunarizine also has documented efficacy, but this "hidden neuroleptic" can cause extrapyramidal disorders and weight gain. (7) Among the serotonergic antagonists, methysergide has documented efficacy but long-term treatment can lead to serious retroperitoneal, pulmonary or cardiac fibrosis. Pizotifen causes drowsiness or weight gain in about 50% of patients. (8) The choice of preventive treatment for migraine must be based on the balance between efficacy (compared to placebo) and adverse effects. In practice, the first choice drug is propranolol. (9) Because the frequency of migraines fluctuates over time, withdrawal of prophylaxis should be attempted on a regular basis, with the patient's consent.

Topics: Adrenergic beta-Antagonists; Amitriptyline; Anticonvulsants; Antidepressive Agents; Cost-Benefit Analysis; Flunarizine; France; Humans; Methysergide; Migraine Disorders; Pizotyline; Propranolol; Serotonin Antagonists; United Kingdom; Valproic Acid

Cyclical vomiting syndrome (CVS), and abdominal migraine (AM) are relatively unusual periodic syndromes, generally believed to be migraine equivalents, and are characterized by recurrent and severe paroxysmal episodes of vomiting and/or abdominal pain lasting hours to days, separated by weeks to months of no symptoms. Flunarizine is a calcium channel-blocking agent that has been used successfully as a prophylactic agent in the prevention of both childhood and adult-onset migraine syndromes. The purpose of this study was to evaluate the efficacy of flunarizine as a prophylactic/preventive agent in the treatment of CVS and AM. Eight children with CVS and 10 children with AM were included in the study. The mean dose of flunarizine was 5 mg/day in children with CVS, and 7.5 mg/day in children with AM. Follow-up ranged from 6 to 24 months (mean 13 months). There was a 57% reduction in frequency and 44% reduction in duration of attacks of CVS, and a 61% reduction in frequency and 51% reduction in duration of attacks of AM. Sixty-four percent of patients with CVS and AM had history of episodic recurrent headaches with 60% reduction in frequency of attacks on treatment. Flunarizine showed to be equally efficacious than previously tried therapies in the prophylaxis of a small cohort of patients with CVS and AM.

Topics: Calcium Channel Blockers; Child; Child, Preschool; Female; Flunarizine; Humans; Male; Migraine Disorders; Periodicity; Retrospective Studies; Syndrome; Treatment Outcome; Vomiting

Topics: Calcium Channel Blockers; Flunarizine; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

Ehlers-Danlos syndrome is a rare inherited illness, which includes an autosomal dominant and also a recessive X-linked variant. Its main clinical characteristic is a generalised connective tissue involving collagen and elastin, causing fragile and hyperextensible skin, loose jointedness and bruising. Many clinical subtypes are described, each of a different severity degree pattern. The correlation of this syndrome and headache disorders is rare. In this paper we describe the case of a young woman with Type II (less severe) Ehlers-Danlos Syndrome and headache.

Topics: Adult; Brain; Calcium Channel Blockers; Ehlers-Danlos Syndrome; Female; Flunarizine; Headache; Humans; Magnetic Resonance Imaging; Migraine Disorders; Mouth; Radiography

Topics: Adult; Age Factors; Child; Child, Preschool; Contraindications; Controlled Clinical Trials as Topic; Double-Blind Method; Flunarizine; Histamine H1 Antagonists; Humans; Migraine Disorders; Placebos; Time Factors; Vasodilator Agents

To determine the effectiveness of flunarizine for migraine prophylaxis in children.. Children aged between 7 and 15 years who had the indication for prophylactic treatment of migraine were recruited into a prospective study at the Department of Pediatrics, Ramathibodi Hospital, from January 1st to December 31st 1999. After verbal consent was obtained, flunarizine was administered either at 5-mg daily in those who had never received it or at 10-mg daily in those who previously took this drug within one year Serial evaluation for the severity of migraine including duration, intensity, and frequency of headache attacks was performed every 2 weeks for 6 months.. Twenty-one children (10 boys, 11 girls) with a mean age of 11.3+/-2.48 years (range 7-15 years) were enrolled in the study. There were ten children who had migraine with aura. Initially, 5-mg daily and 10-mg daily of flunarizine were administered in 19 and 2 patients respectively. The dosage was increased to 10-mg daily after two weeks in 5 patients because of the unresponsiveness to the initial dose. Improvement was observed in 14 patients (66%) including 13 of 14 patients who received 5-mg daily and 1 of 7 patients who received 10 mg daily. Five patients (23%) had no recurrent attack. Nine patients (42%) had more than 50%-reduction of frequency of migraine and 3 of these had either shorter duration or less intensity of the attack. Clinical improvement was observed between 2 and 4 weeks after initiation of treatment. There was no adverse effect observed. This is a preliminary result demonstrating that flunarizine is one of the effective drugs for migraine prophylaxis in children.

Topics: Adolescent; Child; Female; Flunarizine; Humans; Male; Migraine Disorders; Prospective Studies; Treatment Outcome; Vasodilator Agents

Fifty-one patients with migraine were divided into four groups to investigate the effects of topical betaxolol and systemic calcium channel blocker flunarizine on visual fields (VF) and intraocular pressure (IOP). The first group (Group 0) was followed with no medications, topical betaxolol (bid) was precribed to the second group (Group B), oral flunarizine (10 mg daily) was prescribed to the third group (Group F), and the last group (Group BF) was assigned for combined betaxolol and flunarizine treatment. After a mean follow-up time of 4.2 +/- 1.2 months (3-6 months), IOP measurements and VF tests were repeated. Group B and Group BF were found to be statistically different from the other groups in terms of IOP reduction and VF improvement according to mean deviation and corrected pattern standard deviation indices in the second examinations. On the other hand, Group F and Group BF differed from the other two groups considering the improvement in migrainous complaints. VF findings which are probably influenced by perfusion problems due to vasospastic mechanisms in migraineurs, improved following topical betaxolol treatment. However, systemic use of flunarizine--a calcium channel blocker--did not seem to be effective on visual fields although it had beneficial effects on migraine.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Betaxolol; Calcium Channel Blockers; Drug Therapy, Combination; Female; Flunarizine; Humans; Intraocular Pressure; Male; Middle Aged; Migraine Disorders; Visual Fields

Episodic spontaneous hypothermia is an infrequent disorder, with unknown pathogenic mechanisms. A systemic cause or underlying brain lesion has not been found for the disease. We report four new patients, 3-9 years old, with episodic hypothermia lower than 35 degrees C, marked facial pallor, and absent shivering. The episodes could last a few hours or four days, and recurred once a week or every 2-3 months. Two patients also demonstrated bradycardia, mild hypertension, and somnolence during the events; in one of them, profuse sweating was also a feature, and all four presented with either headache, a periodic childhood syndrome, or both (recurrent abdominal pain, cyclic vomiting, or vertigo). Three patients reported a family history of migraine. Neurologic examination, endocrine function, and imaging studies were normal. Migraine prophylactic therapy was of moderate efficacy. Spontaneous resolution was observed in one patient. The clinical characteristics of the syndrome allow for its inclusion as a childhood periodic syndrome related to migraine.

Topics: Abdominal Pain; Body Temperature; Bradycardia; Child; Child, Preschool; Consciousness Disorders; Cyproheptadine; Diagnosis, Differential; Female; Flunarizine; Genetic Predisposition to Disease; Humans; Hyperhidrosis; Hypertension; Hypothermia; Infant; Male; Migraine Disorders; Neurologic Examination; Periodicity; Reference Values; Remission, Spontaneous; Syndrome

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Atenolol; Diagnosis, Differential; Dihydroergotamine; Flunarizine; GABA Agents; Humans; Indoramin; Methysergide; Migraine Disorders; Oxazolidinones; Serotonin Antagonists; Serotonin Receptor Agonists; Tryptamines; Valproic Acid; Vasoconstrictor Agents; Vasodilator Agents

The novel antimigraineur, dotarizine, inhibited 5-HT (5 hydroxytryptamine)-evoked contractions of rabbit vertebral, aorta, femoral and mesenteric arteries, with IC(50)s of 1.35, 1.40, 0.52 and 1.09 microM, respectively. Flunarizine had little effect on these contractions, while ketanserin was more potent (IC(50)s of 0.17 microM for vertebral, 0.22 microM for aorta, 0.05 microM for femoral and 0.03 microM for mesenteric arteries). At 10 microM, dotarizine caused 40% blockade of K(+)-evoked contractions of rabbit aorta, and 70% inhibition of 5-HT-evoked responses; these values were 30% and 20% for 10 microM flunarizine. Contractions of rabbit aorta elicited by noradrenaline, angiotensin II or prostaglandin F(2alpha) were not affected by 10 microM dotarizine or flunarizine. Ketanserin shifted to the right, in parallel, the concentration-response curves for 5-HT in rabbit aorta; however, dotarizine caused a non-competitive type of blockade, increasing the maximum 5-HT contraction at 30 nM and decreasing it at 3 and 30 microM. K(+)-evoked contractions of rabbit aorta were halved by 3 microM dotarizine in a voltage-independent manner; flunarizine caused a delayed-type, non-reversible post-drug blockade, and exhibited some voltage-dependence. Blockade by nifedipine was voltage-dependent and fully reversible. Ca(2+)-evoked contractions of depolarised bovine middle cerebral arteries were blocked by 1--3 microM dotarizine in a non-surmountable manner. Contraction of these vessels evoked by electrical stimulation was blocked 50% and 70% by 1 and 3 microM dotarizine, respectively. Dotarizine (1--3 microM) also inhibited to a similar extent the K(+)-evoked [(3)H]noradrenaline release from cultured rat sympathetic neurones. These data suggest that the mechanism of blockade by dotarizine of cerebral vessels contractility has three components: (i) presynaptic inhibition of noradrenaline release; (ii) blockade of postsynaptic vascular 5-HT receptors; (iii) blockade of Ca(2+)entry into the vascular smooth muscle cell cytosol. The compound does not affect the vascular receptors for noradrenaline, angiotensin II or prostaglandin F(2alpha).

Topics: Animals; Benzhydryl Compounds; Blood Vessels; Calcium Channel Blockers; Cattle; Cerebrovascular Circulation; Electric Stimulation; Electrophysiology; Flunarizine; In Vitro Techniques; Male; Middle Cerebral Artery; Migraine Disorders; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Piperazines; Rabbits; Serotonin; Serotonin Antagonists; Vasodilator Agents

Topics: 5-Hydroxytryptophan; Adolescent; Age Factors; Antidepressive Agents; Female; Flunarizine; Humans; Male; Migraine Disorders; Time Factors; Vasodilator Agents; Vertigo

Flunarizine and cinnarizine (IC50 6.8x10(-6) and 2.8x10(-5) M, respectively) inhibited 3H-serotonin uptake by platelets. In higher doses, they blocked serotonin-induced platelet aggregation and stimulated 3H-serotonin release from these cells. Imipramine did not affect serotonin-releasing effects of preparations. In all patients cinnarizine was more potent in inhibiting serotonin uptake, and in half of the patients cinnarizine displayed higher activity as an inductor of serotonin release.

Topics: Biological Transport; Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Male; Migraine Disorders; Platelet Aggregation; Serotonin

Transcranial Doppler (TCD) recording was used to evaluate the mean flow velocity (MFV) and cerebrovascular reactivity to CO2 in 21 migraineurs during the interictal phase. Nine were affected by migraine with aura (MwA) and 12 by migraine without aura (MwoA). During each session the middle cerebral artery (MCA) flow velocity was examined in basal conditions, in hypocapnia after a 3-min period of hyperventilation, in basal conditions a second time, and in hypercapnia after breath-holding. The same procedure was followed in a group of 21 age- and sex-matched volunteers. Recordings were performed before (T1), during (T2), and after (T3) prophylactic treatment with flunarizine (10 mg/day for 2 months) to assess the possible effect of this drug on cerebral hemodynamics. In basal condition, increased MFV values were found in both MwA and MwoA patients. In MwA patients the reactivity index (RI) to hypocapnia was significantly increased in T1 (p < 0.05). This abnormal cerebrovascular reactivity disappeared during flunarizine treatment (T2) and in the post-therapy period (T3).

Topics: Adult; Blood Flow Velocity; Brain; Calcium Channel Blockers; Carbon Dioxide; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Ultrasonography, Doppler, Transcranial; Vascular Resistance

1. The novel antimigraineur, dotarizine (30 microM), increased cytosolic Ca2+ concentration, [Ca2+]c, in fura-2-loaded bovine adrenal chromaffin cells. This increase was transient, reached a peak in about 2 - 5 min (0.53+/-0.07 microM; n=19) and then declined to basal levels over a further 5 min period. 2. This transient rise of [Ca2+]c was mimicked by 1 microM thapsigargin and by 30 microM cyclopiazonic acid (CPA), but not by 30 microM flunarizine. Both thapsigargin and CPA occluded the effects of dotarizine and vice versa. 3. All three compounds suppressed the transient [Ca2+]c rises induced by caffeine (10 mM, 10 s); blockade induced by thapsigargin was irreversible and that induced by CPA and dotarizine was reversible. 4. Of the three compounds, only dotarizine blocked reversibly the [Ca2+]c spikes induced by short pulses of high K+ (70 mM, 5 s), suggesting that dotarizine blocks voltage-dependent Ca2+ channels but CPA and thapsigargin do not. 5. Dotarizine caused a gradual and reversible depletion of endoplasmic reticulum (ER) Ca2+ in chromaffin cells transfected with ER-targeted aequorin. CPA had a similar effect. 6. These data show that dotarizine shares with thapsigargin and CPA the ability to deplete Ca2+ in the ER; this novel action of dotarizine could be relevant to its prophylactic effects in migraine. Unlike thapsigargin and CPA, however, dotarizine additionally and reversibly blocks Ca2+ entry through voltage-dependent Ca2+ channels.

Topics: Adrenal Medulla; Animals; Benzhydryl Compounds; Caffeine; Calcium; Cattle; Cells, Cultured; Chromaffin Cells; Flunarizine; Indoles; Migraine Disorders; Piperazines; Potassium; Thapsigargin; Vasodilator Agents

KB-2796, a novel calcium channel blocker, is under development as an anti-migraine drug. We examined its effects on spreading depression (SD) in rat hippocampal slices as compared with those of flunarizine, dimetotiazine and sumatriptan. Extracellular recording was made from the CA1 subfield. An SD, followed by a series of spontaneous SDs, was induced by a brief period of hypoxia (40-60 sec). The latency of initiated SD and the interval between the initiated and subsequent spontaneous SDs were examined. KB-2796 significantly prolonged both latency and interval in a concentration-dependent manner (10(-10)-10(-8) M). KB-2796 was about 1,000 and 10 times more potent than flunarizine in prolonging the latency and interval, respectively. However, dimetotiazine and sumatriptan did not show any activity at 10(-7) and 10(-6) M. the effect of KB-2796 on SD may be due to their calcium channel blocking effects.

Topics: Animals; Calcium Channel Blockers; Cortical Spreading Depression; Flunarizine; Hippocampus; Histamine H1 Antagonists; Humans; In Vitro Techniques; Infant, Newborn; Male; Migraine Disorders; Phenothiazines; Piperazines; Rats; Rats, Sprague-Dawley; Sumatriptan

A 26-year-old patient complained of a series of migraine attacks with aura accompanied by slight pleocytosis and gadolinium (Gd-DTPA) enhancement next to the left middle cerebral artery. The migraine attacks and Gd-DTPA enhancement were reversible during prophylactic treatment with flunarizine.

Topics: Adult; Brain; Contrast Media; Female; Flunarizine; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Migraine Disorders; Vasodilator Agents

Lomerizine, a novel Ca2+ channel blocker, is under development as an anti-migraine drug. We examined the effects on spreading depression (SD) induced by a brief period of hypoxia (40 to 60 sec) in rat hippocampal slices, the cortical hypoperfusion and cortical c-Fos-like immunoreactivity that follow KCl-induced SD in anesthetized rats as compared with those of flunarizine. Extracellular recording was made from the CA1 subfield. The latency of initiated SD was examined. Lomerizine (1 and 10 nM) and flunarizine (1 microM) significantly prolonged the latency in a concentration-dependent manner. After KCl application to the cortex, cerebral blood flow monitored by the laser Doppler flowmetry was approximately 20 to 30% below baseline for at least 60 min. Lomerizine (0.3 and 1 mg/kg, i.v.) and flunarizine (1 and 3 mg/kg, i.v.) administered 5 min before KCl application inhibited the cortical hypoperfusion that followed KCl application. c-Fos-like immunoreactivity, an indicator of neuronal activation, was detected in the ipsilateral, but not in the contralateral frontoparietal cortex 2 hr after KCl application. Lomerizine (3-30 mg/kg, p.o.) and flunarizine (30 mg/kg, p.o.) significantly attenuated the expression of c-Fos-like immunoreactivity in the ipsilateral frontoparietal cortex. Lomerizine was 3 to 1000 times more potent than flunarizine in the above SD models. These findings suggest that the inhibitory effects of lomerizine and flunarizine on the interval between the initiated and subsequent spontaneous SDs, the cortical hypoperfusion and expression of c-Fos-like immunoreactivity induced by SD are mediated via the effects of Ca2+ entry blockade, which may include an increase in cerebral blood flow and the prevention of excessive Ca2+ influx into brain cells.

Topics: Animals; Calcium Channel Blockers; Cerebrovascular Circulation; Cortical Spreading Depression; Flunarizine; Hippocampus; In Vitro Techniques; Migraine Disorders; Piperazines; Proto-Oncogene Proteins c-fos; Rats

Vestibular symptoms frequently occur in patients with migraine headache. The common migraine is defined in neurology as a unilateral, pulsating headache, which may be associated with nausea and vomiting, and lasts one or several days. In the classic form patients have visual prodromal symptoms. Focal neurological signs in the migraine complique include, for example, oculomotor palsy and vestibular abnormalities. This so-called vestibular migraine is different from basilar migraine, which involves the irritation of the cervical sympathetic system, and can cause symptoms that resemble transient brainstem ischemia. In order to evaluate vestibular dysfunction electronystagmography (ENG) was used. Patients frequently had abnormal caloric test responses, especially with a directional preponderance, and most had a spontaneous nystagmus. In the migraine attack the patients are presumed to have hypersensitivity of the labyrinth with nausea and vomiting, while in the headache-free period the ENG was almost normal. At present, we have had a high success rate in treating patients with pyracetam. Diazepam was used to treat basilar migraine and flunarizine to prevent vestibular migraine.

Topics: Adolescent; Adult; Aged; Basilar Artery; Calcium Channel Blockers; Caloric Tests; Child; Diazepam; Ear, Inner; Electronystagmography; Female; Flunarizine; Hearing Loss, Sensorineural; Humans; Ischemic Attack, Transient; Male; Middle Aged; Migraine Disorders; Muscle Relaxants, Central; Nausea; Neuroprotective Agents; Nystagmus, Pathologic; Ophthalmoplegia; Piracetam; Sympathetic Nervous System; Vestibular Diseases; Vomiting

Topics: Adrenergic beta-Antagonists; Amitriptyline; Calcium Channel Blockers; Dihydroergotamine; Ergotamine; Flunarizine; Humans; Methysergide; Migraine Disorders; Nicardipine; Nimodipine; Serotonin Antagonists; Serotonin Receptor Agonists; Sumatriptan; Vasoconstrictor Agents

Flunarizine, a calcium channel blocker, is widely used in migraine prophylaxis. Although an antidopaminergic effect has been suggested for this drug, it is unclear whether the antimigraine action of flunarizine involves the dopaminergic system. We studied the inhibitory response of prolactin to acute administration of bromocriptine, a D2 dopamine receptor agonist, before and after 1 month of treatment with flunarizine in migrainous women. Flunarizine treatment increased basal prolactin levels, but it did not reduce the inhibitory response of prolactin to acute bromocriptine administration. These findings do not support the hypothesis that flunarizine acts as a direct antagonist at the D2 dopamine receptor.

Topics: Adult; Bromocriptine; Calcium Channel Blockers; Dopamine Agonists; Drug Interactions; Female; Flunarizine; Humans; Migraine Disorders; Prolactin

Flunarizine is an anti-migraine agent that blocks the Ca2+ entry across cell membrane. In order to obtain a clue of mechanisms underlying the migraine headache, modifications by flunarizine of the response to nitric oxide (NO), a cerebral vasodilator and algogenic agent, derived from perivascular nerves were evaluated. Relaxations due to nerve stimulation by electrical pulses (5 Hz) and nicotine (10(-4) M) in canine cerebral arterial strips were attenuated by treatment with flunarizine dose-dependently, whereas the responses to exogenous NO (10(-7)-10(-6) M) and nitroprusside (10(-8)-10(-6) M) were unaffected. The inhibition by the Ca2+ entry blocker of the response to electrical nerve stimulation and nicotine was obtained in a concentration (10(-6) M) that did not significantly relax the arterial strips. NO derived from perivascular nerve may be one of the factors involved in the genesis of migraine attack, which is expected to be relieved by a reduction of neural NO synthase activity associated with a decreased Ca2+ influx by flunarizine during nerve activation.

Topics: Animals; Calcium Channel Blockers; Cerebral Arteries; Dogs; Electric Stimulation; Female; Flunarizine; In Vitro Techniques; Male; Migraine Disorders; Nicotine; Nitric Oxide; Nitroprusside

Topics: Adolescent; Anticonvulsants; Calcium Channel Blockers; Dose-Response Relationship, Drug; Electromyography; Female; Flunarizine; Humans; Migraine Disorders; Myoclonus; Palate, Soft; Tremor

This international postmarketing observational study of flunarizine was designed to evaluate, in routine clinical practice, the risk/benefit ratio of flunarizine in its approved indications, namely prophylaxis of migraine and treatment of vertigo. Comparator drugs were propranolol in migraine and betahistine in vertigo. The study was carried out by 498 general practitioners in Belgium, The Netherlands and Germany, whose participation had been requested by mail. In total 3186 patients were entered: 1601 in the two migraine cohorts and 1585 in the two vertigo cohorts.. In the migraine study, treatment results with propranolol tended to be somewhat better than those with flunarizine, but a selection bias cannot be excluded. There was no clear difference regarding efficacy between flunarizine and betahistine in the vertigo study. The safety evaluation focused on extrapyramidal symptoms (EPS) and depression. Overall, EPS were noted in only four patients, two in the vertigo-betahistine and two in the migraine-flunarizine cohort. A total of 70 patients developed depressive symptoms (34 in the flunarizine and 24 in the propranolol migraine cohorts, but only 7 in the flunarizine and 5 in the betahistine vertigo cohorts). Patients with migraine were clearly more prone to depression than patients with vertigo, regardless of their treatment. Additional risk factors for depression were a history of depression, and, in the migraine flunarizine cohort, a high number of previous migraine treatments.

Topics: Basal Ganglia Diseases; Betahistine; Cohort Studies; Depression; Female; Flunarizine; Histamine H1 Antagonists; Humans; Male; Migraine Disorders; Product Surveillance, Postmarketing; Propranolol; Prospective Studies; Risk Factors; Vasodilator Agents; Vertigo

Topics: Child; Diagnosis, Differential; Electroencephalography; Flunarizine; Functional Laterality; Hemiplegia; Humans; Migraine Disorders; Mitochondrial Encephalomyopathies; Moyamoya Disease; Prognosis; Tomography, Emission-Computed, Single-Photon

Topics: Affect; Depressive Disorder; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Problem Solving; Substance-Related Disorders

In infancy, two brothers developed recurrent attacks of alternating or bilateral hemiplegia arising exclusively out of sleep. The episodes were terminated by even brief sleep. Neither child had hypotonia, dystonic attacks, paroxysmal eye movement abnormalities, or other features characteristic of the now-classic form of alternating hemiplegia of childhood (AHC). The development of the brothers has so far remained normal. Both parents have a history of migraine. In the older boy, magnetic resonance spectroscopy (MRS) of muscle showed increased inorganic phosphate similar to what is found in children with AHC. In the younger brother and parents, MRS of muscle was normal. Other investigations were unrevealing. Flunarizine greatly reduced the duration of attacks. This genetically determined disorder represents a specific entity that is probably migraine-related and is easily misdiagnosed as AHC. Because of its benign course, particularly as far as mental development is concerned, it must be distinguished from classic AHC, which has a terrible prognosis.

Topics: Adult; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Benzodiazepinones; Clobazam; Electroencephalography; Female; Flunarizine; Hemiplegia; Humans; Infant; Magnetic Resonance Spectroscopy; Male; Migraine Disorders; Muscle, Skeletal; Phosphates; Recurrence; Sleep Wake Disorders

We studied in vivo the influence of flunarizine on dopamine D2 receptors and investigated whether dopamine D2 receptor blockade is involved in its antimigraine action. Eleven migraine patients, treated with flunarizine, 10 mg per day, underwent single photon emission computer tomography (SPECT) using [123I] labeled iodobenzamide, a ligand with high affinity and high specificity for D2 receptors. There was a reduction of the dopamine D2 receptor binding potential in all patients compared to age-matched controls. The efficacy of flunarizine in migraine prophylaxis failed to correlate with the degree of the dopamine D2 receptor blockade. The antimigraine action of flunarizine may not involve antidopaminergic mechanisms.

Topics: Adult; Aged; Brain; Dopamine D2 Receptor Antagonists; Female; Flunarizine; Humans; Iodine Radioisotopes; Male; Middle Aged; Migraine Disorders; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon

The prophylactic value of a daily dose of 10 mg flunarizine, a calcium antagonist, was analysed in 100 migraineurs during 4-month in an open study. Ninety-three patients completed the full 16-week course of therapy, and seven patients presented important adverse reactions requiring discontinuation of the drug. However, the seven patients who dropped out during flunarizine treatment were not considered in the analysis. Side-effects included weight gain, sleepiness, humor depression, paresthesias and dry mouth. Eighty-one patients experienced abolition or significant reduction in headache incidence and/or severity. We conclude that flunarizine may be an effective drug in migraine prophylaxis.

Topics: Adolescent; Adult; Female; Flunarizine; Humans; Male; Migraine Disorders; Prospective Studies

Topics: Adult; Calcium Channel Blockers; Female; Flunarizine; Humans; Indomethacin; Male; Middle Aged; Migraine Disorders; Nicardipine

The recent development of SPECT has introduced a new procedure to evaluate neurological diseases. By mean of Tc99mHM-PAO we studied a group of 19 pediatric subjects (7 males and 12 females) with different form of migraine, within five days after the last headache attack. Postictally SPECT shows regionally decreased CBF in 3/4 of HM, in 5/6 of BAM, in 5/5 of CM and in 2/4 of M.

Topics: Adolescent; Cerebrovascular Circulation; Child; Female; Flunarizine; Humans; Male; Migraine Disorders; Organotechnetium Compounds; Oximes; Pizotyline; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Changes in the diameter of extracranial and intracranial arteries resulting in changes in cerebral blood flow have previously been assumed to be the most important pathophysiological factor in migraine. To test this hypothesis 20 normal subjects, and three groups of patients (n = 29) with migraine were investigated by means of transcranial Doppler sonography. Blood flow velocities in the middle cerebral (MCA) and in basilar (BA) arteries were measured. Data from patients were obtained in the interval between migraine attacks, during migraine attacks and following treatment with either ergotamine (0.5 mg i.m.; n = 10); flunarizine, a calcium overload blocker (20 mg i.v.; n = 13); or a 5-HT1-like agonist (sumatriptan, 4 mg s.c.; n = 6). Ergotamine and sumatriptan are constrictors of cerebral arteries in animal experiments. The arithmetic mean of flow velocity in the BA was reduced in normal subjects (45 cm/s) as compared with patients with migraine measured in between attacks (53 cm/s). Mean flow velocity in MCA was not different in normals (72.5 cm/s) as compared with migraineurs (75 cm/s). Neither ergotamine nor the 5-HT1 agonist and flunarizine resulted in a significant change in blood flow velocity in MCA and BA. This was true irrespective of whether the drugs were given in the headache-free period, during a migraine attack or during the withdrawal phase of drug-induced headache. Ergotamine was effective in improving headache during migraine attacks and sumatriptan attenuated headache during drug withdrawal from chronic analgesic intake. These results indicate that the action of ergotamine and the 5-HT1-receptor agonist is probably not mediated by their vasoconstrictor action on cerebral arteries.

Topics: Adult; Blood Flow Velocity; Cardiovascular Agents; Cerebrovascular Circulation; Ergotamine; Female; Flunarizine; Humans; Indoles; Male; Middle Aged; Migraine Disorders; Reference Values; Sulfonamides; Sumatriptan; Vasoconstrictor Agents

We followed-up 64 migraine patients after discontinuation of successful interval prophylaxis with flunarizine, propranolol or metoprolol, to investigate how long the therapeutic success would last, if further prophylaxis would be successful again, and what factors would influence the prognosis. We found that 16 out of 64 patients experienced a lasting reduction of migraine frequency, whereas 48 patients did improve initially, but later experienced a relapse. Further prophylaxis was effective in 29, poorly effective in 11, and ineffective in 8 of these patients; in 7 of the 8 non-responders prophylaxis was not changed. Negative prognostic factors were frequent attacks, a history of analgesic abuse and/or analgesic withdrawal therapy and ineffective previous prophylaxis. In conclusion, the therapeutic success decreases dramatically in the majority of patients several months after discontinuation of prophylaxis; further prophylaxis is more effective if the substance class is changed; increased analgesic intake is the most important prognostic factor. As a strategy for migraine prophylaxis we propose sequential changing of interval prophylaxis or--in patients with negative prognostic factors--long-term prophylaxis.

Topics: Adult; Aged; Female; Flunarizine; Humans; Male; Metoprolol; Middle Aged; Migraine Disorders; Prognosis; Propranolol; Time Factors

Topics: Aged; Amnesia; Basilar Artery; Female; Flunarizine; Humans; Migraine Disorders

The effect of the calcium entry blockers flunarizine and nimodipine on isolated human cerebral and temporal arteries has been studied. Flunarizine induced only weak relaxation of precontracted temporal arteries in contrast to the response seen in cerebral arteries. Nimodipine invariably induced strong relaxation of both types of vessel. The effect of the calcium entry blockers on potassium (K+)-, noradrenaline (NA)- and 5-hydroxytryptamine (5-HT)-induced contraction was also examined. In general, the K(+)-induced contraction was inhibited by both calcium entry blockers, nimodipine being more potent than flunarizine, the cerebral artery being more sensitive. The response to K+ consisted of two phases; the second, slowly developing phase of contraction was more sensitive to either blocker than the initial, fast phase of contraction. Flunarizine was significantly more potent in inhibiting NA-induced contraction of the human cerebral than of the temporal artery, and there was no difference in its action on 5-HT-induced contraction of either artery. The same pattern was found for nimodipine, which was more potent in every aspect. Both calcium entry blockers induced a parallel shift in calcium-induced contraction studied by application of calcium to vessels preincubated in calcium free medium. Flunarizine was more potent on cerebral than on temporal arteries and there was no difference between the two vessels in this action of nimodipine. However, the latter was more potent than flunarizine in preventing calcium-induced contraction. The clinical implications of the two agents are discussed in relation to cerebrovascular disorders.

Topics: Calcium; Cerebral Arteries; Cerebrovascular Disorders; Flunarizine; Humans; Migraine Disorders; Nimodipine; Norepinephrine; Potassium; Serotonin; Temporal Arteries; Vasoconstriction

Flunarizine, a calcium antagonist widely used in the prophylactic treatment of migraine, may interfere with dopaminergic systems. Flunarizine therapy can in fact induce extrapyramidal side effects and can increase basal as well as stimulated prolactin levels. To better define the mechanism of flunarizine action in migraine, we studied prolactin and growth hormone responses to thyrotropin releasing hormone and sulpiride in 13 female migraineurs before and after 60 days of flunarizine therapy. The treatment did not modify basal prolactin and growth hormone levels, but prolactin response to thyrotropin releasing hormone was enhanced. A paradoxical increase of growth hormone to thyrotropin releasing hormone observed before therapy was blunted after flunarizine treatment. These data indicate a modulatory action of flunarizine on dopaminergic systems which might to some extent explain the antimigraine action of this drug.

Topics: Adult; Analgesics; Calcium Channel Blockers; Dopamine; Female; Flunarizine; Growth Hormone; Humans; Migraine Disorders; Prolactin; Thyrotropin-Releasing Hormone

We report two cases of sleep disturbances and perceptual disorder appearing in close temporal relationship with initiation of flunarizine therapy for migraine prophylaxis: these side effects disappeared after therapy interruption; resumption of the drug in one case was associated with symptom recurrence.

Topics: Female; Flunarizine; Humans; Middle Aged; Migraine Disorders; Perceptual Disorders; Sleep Initiation and Maintenance Disorders

The use of flunarizine, a drug which has proven its efficacy in migraine, is often associated with important side effects. The aim of this paper has been to check their incidence at different dose levels (5 mg vs 10 mg). Our data confirm the occurrence of important side effects (in particular weight gain); on the other hand, they emphasize the dose-dependency of the side effects.

Topics: Adult; Analgesics; Dose-Response Relationship, Drug; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Weight Gain

Topics: Calcium Channel Blockers; Cerebral Infarction; Cerebrovascular Disorders; Epilepsy; Flunarizine; Humans; Intracranial Arteriosclerosis; Migraine Disorders; Nimodipine

Alternating hemiplegia is an infrequent form of complicated migraine. Clinical course has similarities with seizure disorders and correct diagnosis may be difficult. We report three patients whose onset in early childhood was with general impairment, transient hemiplegia, ocular movements and vasomotor symptoms. Clinical course of alternating hemiplegia is characterized by progressive neurologic deterioration. Intermittent motor impairment is alternating in side and later during the episodic attacks headache is present. Laboratory, electrophysiologic and neuroradiologic procedures are not demonstrative. In this report we show the findings in three patients in relation to the symptoms they presented, the utility of paraclinical investigations and their response to flunarizine treatment.

Topics: Age Factors; Child, Preschool; Female; Flunarizine; Hemiplegia; Humans; Infant; Male; Migraine Disorders; Periodicity

Flunarizine plasma concentrations and side effects were evaluated in migraine patients during a 3 month course of prophylactic treatment. Plasma concentrations did not correlate with daily dose (in mg/kg). Mean flunarizine levels were higher in patients showing sleepiness or sedation. Weight gain was independent of plasma concentrations. Future clinical trials of flunarizine should be supported by drug monitoring in order to clarify the relationship between plasma levels and drug effects.

Topics: Adolescent; Adult; Aged; Child; Dose-Response Relationship, Drug; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Osmolar Concentration

The aim of our study was to evaluate the efficacy of long-term migraine prophylaxis with flunarizine. The efficacy of the drug was evaluated on the basis of the frequency, pain severity and duration of migraine attacks. Frequency, the most modified parameter, was reduced to about half of the pre-treatment level in one to three months time. The condition remained more or less stable from the third treatment month onwards. The results showed remarkable efficacy of long-term prophylaxis with flunarizine, and the response was better in younger patients with a short history of migraine.

Topics: Adult; Drug Evaluation; Female; Flunarizine; Headache; Humans; Longitudinal Studies; Male; Migraine Disorders

Spreading depression is a reversible response of brain tissue to a local insult. It has been postulated to be the physiological substrate for the aura phase of classic migraine. The properties and mechanisms of spreading depression were studied in the parietal neocortex of the alfentanil-anesthesized rat, by using a cup electrode that provided close control of the electrical stimulus while allowing specific ion (K+) and potential recordings to be made directly beneath the cathode, the region of origin of the stimulus-induced spreading depression. Cathodal stimulation caused the extracellular K+ concentration to rise, and spreading depressions were observed when this concentration exceeded 8-12 mM in the upper 100-200 microns of cortex. In some experiments extracellular [K+] continued to increase for 5-10 sec after termination of the stimulus, without detectable after-discharge in the potential record, before subsiding. While spreading depression could easily be induced by pressure on the cortex, local damage incidental to opening the dura rarely induced spreading depression. This suggests that a local (1-mm2) neurovascular injury is not likely to induce spreading depression--at least in normal cortex--and so is probably not the source of the spreading depression postulated to generate the aura of classic migraine. Mechanisms of spreading depression, and drugs that influence spreading depression, are reviewed, and possible uses of spreading depression in the pharmacology of the central nervous system are considered.

Topics: Animals; Cerebral Cortex; Cerebrovascular Circulation; Cortical Spreading Depression; Electric Stimulation; Flunarizine; Male; Migraine Disorders; Models, Neurological; Neuroglia; Neurotransmitter Agents; Potassium; Rats; Rats, Inbred Strains

Topics: Adolescent; Adult; Appetite; Blood Glucose; C-Peptide; Dietary Carbohydrates; Female; Flunarizine; Humans; Insulin; Male; Middle Aged; Migraine Disorders; Time Factors; Weight Gain

Topics: Adult; Electroencephalography; Epilepsies, Partial; Epilepsy; Female; Flunarizine; Humans; Migraine Disorders

Topics: Flunarizine; Humans; Migraine Disorders

Four studies were pooled to study the onset of action of three pharmacologically different migraine prophylactics: flunarizine, pizotifen and propranolol. Inter-drug differences in reduction of baseline attack frequency were subjected to analysis of variance. At months 1, 2, and 3 the inter-drug differences in number of patients showing a first 50% decrease in attack rate were subjected to the Chi-square test. Both tests showed that there were no significant differences in onset of action between the three drugs. It is concluded that migraine responds to flunarizine and to other commonly used prophylactics in a similar way and with similar kinetics.

Topics: Adolescent; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Pizotyline; Propranolol; Thiophenes

Six double-blind studies have been published in which the efficacy of flunarizine and pizotifen were compared. In none of the studies were differences of statistical significance revealed for attack frequency. Secondary analysis of the three studies in which the same protocol was employed, using parametric tests on transformed data gave similar results. Pooling of the data in an attempt to enhance the power by enlarging the number of patients, actually decreased the power due to an increase in standard deviation.

Topics: Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Pizotyline; Thiophenes

Spectral EEG analysis has been successfully utilized in previous studies on migraine patients. The aim of our study was to evaluate, by means of EEG mapping, potential correlations between the efficacy of flunarizine treatment in migraine patients and the EEG pattern recorded after chronic flunarizine therapy. Flunarizine was found to modify the non-specific EEG abnormalities of our migraine patients as well as evoke a positive clinical response.

Topics: Adult; Electroencephalography; Flunarizine; Humans; Migraine Disorders

Topics: Adolescent; Female; Flunarizine; Hemiplegia; Humans; Migraine Disorders

From 6 months of age on this girl experienced frequent episodes of hemiplegia involving both sides of the body and lasting up to 8 days. The attacks were often precipitated by tonic deviation of the head and/or the eyes to one side and nystagmus. At this stage the girl used to cry. Squinting, tonic stiffening of body and extremities, and dystonic posturing also occurred. Autonomic dysfunctions such as paleness of the skin, sweating, respiratory embarrassment, tachycardia, and mydriasis were associated features of the attacks. Motor and mental development of the girl is delayed. Improvement concerning severity, duration and frequency of the attacks has been achieved by permanent treatment with flunarizine in combination with acetazolamide and acetylsalicylic acid. If the child falls asleep immediately after rectal application of chloral hydrate at the onset of an attack there is no hemiplegia after awakening.

Topics: Acetazolamide; Aspirin; Brain Ischemia; Cerebral Cortex; Child, Preschool; Chloral Hydrate; Drug Therapy, Combination; Female; Flunarizine; Hemiplegia; Humans; Migraine Disorders; Tomography, Emission-Computed

Topics: Adult; Female; Flunarizine; Humans; Male; Migraine Disorders; Pituitary Hormones, Anterior; Radioimmunoassay

Topics: Basal Ganglia Diseases; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders

Topics: Adult; Drug Evaluation; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Time Factors

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.

Topics: Adolescent; Adrenal Cortex Hormones; Blood Glucose; Child; Female; Flunarizine; Glycated Hemoglobin; Gonadal Steroid Hormones; Humans; Male; Migraine Disorders; Pituitary Hormones; Thyroid Hormones

Topics: Adult; Depression; Female; Flunarizine; Humans; Migraine Disorders; Tremor

A short episode of focal cortical hypoxia seems to be the turning-point in the genesis of the migraine attack. This pathophysiological situation induces vascular changes according to the hypothesis of Wolff. Under such conditions some Ca-antagonists develop antihypoxic and antivasoconstrictive properties. The efficiency of Flunarizine as potent prophylactic drug in migraine therapy is well documented in many double-blind randomized studies versus placebo or other antimigrainous drugs. Based on the positive results of these studies, we liked to investigate the efficiency and tolerability of Flunarizine also in a sample on n = 44 adults Austrian patients recruited from the Headache-Ambulance of the Neurological Department, University of Vienna. After a 3 months treatment with Flunarizine, 10 mg daily, there was a drug free follow-up period of 4 to 12 months. After this time in 29 patients (66.6%) there was a decrease of attack frequency of more than 50%. 12 (27.3%) of them were completed free of attacks. Beside this, the intake of attack ameliorating drugs (ergotamine, analgetics) was markedly reduced. Treatment was well tolerated. Weight gain was observed in 20.3% of patients likely correlating with the therapeutic efficiency. Due to its efficiency, safety and its long-lasting therapeutic effect, Flunarizine appears to be a very suitable agent in the prophylaxis of migraine.

Topics: Adult; Drug Therapy, Combination; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Pilot Projects

Topics: Biological Availability; Flunarizine; Humans; Male; Migraine Disorders; Tablets

Topics: Adolescent; Adult; Body Weight; Drug Administration Schedule; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Sex Factors

Topics: Adolescent; Adult; Drug Administration Schedule; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Muscle Contraction

Topics: Acute Disease; Administration, Sublingual; Flunarizine; Humans; Migraine Disorders

Topics: Adolescent; Flunarizine; Hemiplegia; Humans; Male; Migraine Disorders

The therapeutic effect of selective calcium entry blockers in the treatment of chronic occlusive diseases of peripheral and cerebral arteries is well documented. Experimental studies in acute cerebral ischaemia and cerebral infarction allow to anticipate positive results in clinical studies. The number of clinical studies so far available is to small for final assessment at the present time.

Topics: Arterial Occlusive Diseases; Calcium; Calcium Channel Blockers; Cerebrovascular Circulation; Flunarizine; Humans; Ion Channels; Migraine Disorders; Muscle, Smooth, Vascular; Nifedipine

Topics: Adrenergic beta-Antagonists; Amitriptyline; Aspirin; Benzoxepins; Calcium Channel Blockers; Cinnarizine; Clonidine; Dihydroergotamine; Flunarizine; Humans; Methysergide; Migraine Disorders; Pizotyline; Propranolol

Topics: Adolescent; Adult; beta-Thromboglobulin; Blood Platelets; Cinnarizine; Female; Flunarizine; Humans; Male; Migraine Disorders; Platelet Factor 4; Platelet Function Tests

Alterations of regional cerebral blood flow (rCBF) are at least epiphenomena of common and complicated migraine, but may lead to serious clinical complications. Since flunarizine seems to be effective in migraine prevention it may exert a beneficial influence on rCBF in migraine as well. rCBF was assessed using the 133Xe inhalation method in 5 patients with common and 8 patients with complicated migraine. Measurements were done interictally prior and after therapy with 15 mg flunarizine p.o. daily over a period of 4 weeks. Major abnormalities of grey matter flow were observed even interictally. Significant improvement of rCBF in initially hypoemic regions may be attributed to flunarizine therapy. These preliminary data suggest that calcium entry blockers may prevent the ischemic complications of migraine.

Topics: Brain; Brain Ischemia; Carbon Dioxide; Flunarizine; Humans; Migraine Disorders; Prospective Studies; Regional Blood Flow

Acute ischemia of the brain induces a cascade of biochemical and physiological events. The final consequences depend on the fact whether ischemia is of transient or permanent, total or partial nature. Alteration of extracellular potassium concentration, intracellular calcium and potassium concentration, development of cytotoxic and vasogenic edema, postischemic hyperfusion and no-reflow phenomenon are important factors which decide about the final fate of functional capacity. CO2 reactivity, autoregulation and hemorheology must be considered when therapeutic approaches are used to influence basic flow during ischemic condition. At present there exists no therapy which has been fully accepted and is able to guarantee benefit to the hypoperfused tissue. Since the calcium metabolism is altered by ischemic processes, substances which act on this metabolism might be of value in the treatment of ischemia and its consequences. However, their beneficial effect on cerebral infarction has not been proven yet. In subarachnoid hemorrhage and migraine calcium antagonists are used to prevent and treat ischemia. In epilepsia calcium overload blockers have been tried by one group with promising results.

Topics: Acute Disease; Brain Edema; Brain Ischemia; Calcium Channel Blockers; Cerebrovascular Disorders; Epilepsy; Flunarizine; Humans; Migraine Disorders; Rheology; Subarachnoid Hemorrhage

Contraction induced by 124 mM potassium followed the depolarization of smooth-muscle cells and activation of potential-operated calcium channels in human temporal arteries. The contraction elicited consisted of two phases, one rapid and one slowly developing stable phase; both were affected by the two calcium entry blockers flunarizine and nimodipine but at significantly different concentrations. In calcium-free medium 124 mM potassium resulted in a weak contraction. Addition of calcium caused a concentration-dependent contraction that was attenuated by the calcium entry blockers at concentrations comparable to those inhibiting the second phase. The results suggested that in human temporal arteries flunarizine and nimodipine act as calcium entry blockers; there was good correlation with the therapeutic plasma concentration for nimodipine but not for flunarizine.

Topics: Calcium; Flunarizine; Humans; Migraine Disorders; Muscle, Smooth, Vascular; Nimodipine; Potassium; Temporal Arteries; Vasoconstriction

Topics: Administration, Oral; Flunarizine; Humans; Migraine Disorders

Topics: Adrenergic beta-Antagonists; Anti-Anxiety Agents; Cinnarizine; Dihydroergotamine; Dose-Response Relationship, Drug; Flunarizine; Humans; Hypotension; Migraine Disorders; Time Factors

In order to study the role of platelets in migraine and cerebrovascular disease, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) plasma levels, indices of in vivo platelet activation, were assayed in two groups of patients suffering from migraine (common/classic and classic/complicated migraine, respectively) and in one group suffering from transitory ischemic attacks (TIAs). Plasma determinations were carried out in the absence of treatment and during the administration of aspirin (50 mg/daily) and flunarizine (10 mg/daily). Platelet activation was found in patients suffering from TIA; patients affected by classic and complicated migraine showed a high incidence of activation, in comparison with common migraine sufferers, also in headache-free periods. Administration of aspirin (ASA) was more effective than flunarizine in inducing a decrease in beta-TG and PF4 plasma levels in migraineurs. Aspirin, however, did not affect platelet activation in subjects suffering from ischemic attack even though we did not observe any relapse after one year of treatment. The different effect of ASA in TIAs and migraine indicates that the platelet activation in TIA patients is due not only to cyclo-oxygenase pathway but also to other in vivo pathways.

Topics: Adult; Aged; Aspirin; beta-Thromboglobulin; Cinnarizine; Female; Flunarizine; Humans; Ischemic Attack, Transient; Male; Middle Aged; Migraine Disorders; Piperazines; Platelet Aggregation; Platelet Factor 4; Vasodilator Agents

Flunarizine (10 mg/day for 60 days) was given to eight postmenopausal women with common migraine. Plasma LH pulsatility fluctuation, peripheral concentrations of prolactin (PRL), cortisol, beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and Pain Total Index (PTI) were evaluated before and after treatment. PTI was significantly reduced by flunarizine, which did not affect beta-LPH, beta-EP and cortisol plasma levels. On the contrary, both PRL values and amplitude, and length of LH pulses had increased at the end of treatment. Flunarizine reduced head pain in postmenopausal women. However, the enhancement of both PRL and LH release indicates that this calcium antagonist might interfere with the dopaminergic tonus.

Topics: beta-Endorphin; Calcium Channel Blockers; Cinnarizine; Endorphins; Female; Flunarizine; Humans; Luteinizing Hormone; Menopause; Middle Aged; Migraine Disorders; Piperazines; Prolactin

Topics: Adult; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Random Allocation; Vasodilator Agents; Verapamil

The vestibular function was extensively investigated in 75 patients suffering from migraine. Pathological findings were present in 62 patients (82.6%). With the exception of position nystagmus, vestibular abnormalities were not related to migraine characteristics. Fifty-six patients were treated with flunarizine 10 mg daily for three months. A favourable effect on headache was obtained in 44 patients (78.5%). Flunarizine therapy influenced significantly gaze nystagmus and position nystagmus. The latter tended to be related to anti-migraine efficacy. Other electronystagmographic parameters were not substantially influenced. The authors assume that the vestibular abnormalities in migraine are side phenomena, the clinical relevance of which, at least during the headache-free phase, is not yet well understood.

Topics: Adolescent; Adult; Aged; Calcium Channel Blockers; Child; Cinnarizine; Electronystagmography; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Vestibular Function Tests; Vestibule, Labyrinth

Two new hypotheses suggest that the key pathology in migraine has a neuronal origin. A pivotal role is assigned to brain hypoxia (1) and spreading depression (SD) (neuronal depolarization spreading gradually over the cortex) (2). Flunarizine has been tested both against brain hypoxia and SD. Its potent antihypoxic properties in animal models led to its use as a prophylactic drug in migraine therapy. Earlier experiments suggested that flunarizine shortened recovery after neuronal depolarization. Recent experiments suggest that flunarizine may enhance the threshold for the elicitation of SD. Finally, it is often unclear whether the effects observed with flunarizine are due to a vascular or a direct neuronal effect. Therefore, a study was made to show whether flunarizine affected hypoxia-induced alterations in synaptic function in slices of hippocampus held in vitro. At physiological drug concentrations in brain, flunarizine improved post-hypoxic recovery of synaptic function. A direct neuronal protective effect was thus demonstrated.

Topics: Animals; Calcium Channel Blockers; Cells, Cultured; Cinnarizine; Cortical Spreading Depression; Disease Models, Animal; Flunarizine; Guinea Pigs; Hypoxia, Brain; Migraine Disorders; Neurons; Piperazines; Rats; Vasodilator Agents

Changes in erythrocyte deformability (ED) parameters have been investigated in 36 patients suffering from different forms of headache (classic and common migraine; migraine with interval headache; chronic tension headache) and treated with flunarizine (10 mg/day at bedtime). Patients were carefully selected in order to avoid any possible interference with the parameters under study, and smoke and drug use in particular (symptomatics included) were considered as criteria for exclusion from the trial. Controls of ED parameters were planned before treatment and after 20 and 35 days. Baseline ED alterations were present only among patients with chronic tension headache, but flunarizine treatment was able to positively modify ED parameters in these patients, as well as in migraine cases that showed normal baseline ED values. No correlation was found between patients' characteristics and baseline ED values, nor between ED changes under treatment and therapeutic effects of flunarizine.

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Erythrocyte Deformability; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

Fifty migraine patients were tested prior to and after a three-month period of flunarizine treatment (10 mg per day) by means of a new computerized telethermography apparatus. At completion of therapy a new computerized telethermography was carried out. The telethermographic data obtained showed an improvement in 70% of the cases; for the other patients telethermographic relevant modifications were not singled out.

Topics: Adult; Aged; Calcium Channel Blockers; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Ophthalmic Artery; Piperazines; Temperature; Thermography

BAEPs have been studied in a group of 20 migraine subjects before and after chronic flunarizine treatment. No statistically significant modifications of neurophysiological parameters have been observed. We confirm flunarizine effectiveness in migraine treatment.

Topics: Adult; Brain Stem; Calcium Channel Blockers; Cinnarizine; Evoked Potentials, Auditory; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

In migraine patients the effect of calcium antagonists (flunarizine, verapamil and nifedipine) on both venous and pupillary neuromuscular functions, as well as on blood pressure have been evaluated. A single oral dose of flunarizine (10 mg) and verapamil infusion (50 micrograms/ml/min) increased venous compliance. Verapamil also counteracted dose-dependent dopamine induced venoconstriction. Nifedipine (10 mg orally) reduced mean arterial pressure in upright position in migraineurs but not in controls. In addition, chronic treatment with flunarizine (10 mg for 2 weeks) induced a transient miotic effect and a reduction of tyramine induced mydriasis. These findings demonstrated that calcium antagonists affect vascular and extravascular structures. It is postulated that, in migraine, calcium entry blockers may prevent exaggerated responses to catecholaminergic stimulation.

Topics: Blood Pressure; Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Migraine Disorders; Nifedipine; Pupil; Vasoconstriction; Verapamil

The effect of 30-days of flunarizine (5 mg/day) therapy on pituitary, B-pancreatic, gonadic and adrenal function was studied in five adolescents with common migraine. Baseline concentration of growth hormone was significantly reduced after flunarizine therapy. The response of prolactin to thyrotrophin-releasing hormone was significantly increased after flunarizine therapy. The percentages of HbA1 and HbA1c were significantly higher after flunarizine therapy. The drug had no apparent effect on gonadic and adrenal function. Further studies are needed to confirm the effect of flunarizine on the hypothalamus-pituitary axis and glucose tolerance.

Topics: Adolescent; Adrenal Cortex Hormones; Calcium Channel Blockers; Child; Cinnarizine; Female; Flunarizine; Glycated Hemoglobin; Gonadal Steroid Hormones; Humans; Male; Migraine Disorders; Piperazines; Pituitary Hormones

Fifty-two patients, most of whom had had daily headaches for years, were examined and treated. Among them there were 40 who originally had migraine, the others had vasomotor or post-contusional headaches. Average duration of the migraine was 21 years, of chronic headache 7.6 years. All patients had been taking analgesics of a mixed type regularly and for a long time, on average 35.6 tablets or suppositories weekly. All patients had taken more than three different drugs. After an observation period of 3-6 months for grading the headaches and registering the amount of drug intake, all patients were admitted to hospital when all analgesics were at once discontinued. Changing degrees of withdrawal symptoms were the rule: increased headaches, nausea, vomiting, tachycardia, sweating, sleep disorders, and in some also hallucinations and cerebral episodes. At the end of the hospital stay chronic headache had completely disappeared or markedly improved in 77% of patients. Even after an average of 16 months of subsequent observation, chronic headache continued to be significantly improved in 70% of patients. There was a significant reduction in frequency and intensity of attacks in the patients with originally typical migraine. Regular intake of analgesics of the mixed type induces chronic headaches. These are most commonly caused by ergotamine tartrate and aminophenol derivatives, while psychological and physical dependence on anti-migraine drugs is initiated and maintained by additional barbiturates, caffeine and codeine.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Analgesics; Chronic Disease; Cinnarizine; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Pizotyline; Substance Withdrawal Syndrome

The effects of flunarizine in migraine headache were investigated in 40 patients treated with single 10 mg evening doses for 16 weeks. Standard criteria were adopted for patient admission and for the monitoring of clinical (headache index, consumption of analgesics, side-effects) and laboratory variables (platelet aggregation and red cells filterability). Significant positive effects were found in 31/40 cases irrespective of the clinical course of the disease (i.e., recurrent attacks or more or less chronic forms). Some baseline characteristics of the patients are discussed on the basis of the therapeutic response.

Topics: Adult; Analgesics; Asthenia; Cinnarizine; Erythrocyte Deformability; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Platelet Aggregation; Time Factors; Wakefulness

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Pizotyline; Thiophenes

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

Topics: Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Migraine Disorders; Piperazines