Efficacy of nimodipine in comparison with pizotifen in the prophylaxis of migraine

The efficacy of nimodipine in comparison with that of pizotifen was assessed in the prophylaxis of migraine in a double-blind cross-over study, in which a double-dummy technique was also utilized. The study was carried out on 43 migraine patients, of whom 15 had classic and 28 had common migraine. A 4-week run-in placebo period preceded the drug treatments, the drug treatments lasted 12 weeks, and there was a washout placebo period of 4 weeks between nimodipine and pizotifen treatments. The dosages used were 40 mg three times daily for nimodipine and 0.5 mg three times daily for pizotifen. Both nimodipine and pizotifen proved to be better than placebo, the number of migraine attacks showing a significant reduction. There was no difference between nimodipine and pizotifen in antimigrainous efficacy, but there were fewer side effects during the nimodipine period. The results suggest that nimodipine is an effective drug for the prophylaxis of migraine, with few side effects and therapeutic efficacy equal to that of pizotifen.     

Zonisamide for migraine prophylaxis in refractory patients

Zonisamide is a new antiepileptic drug with multiple mechanisms of action and a favourable pharmacokinetic profile. Preliminary data suggest that zonisamide may be effective in migraine prophylaxis. We evaluated the efficacy and tolerability of zonisamide for migraine prophylaxis in refractory patients. We reviewed the charts of adult patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) according to the Silberstein-Lipton criteria, who had been treated with zonisamide at our out-patient clinic for at least 60 days. Demographic data, zonisamide dosage and duration of treatment were collected and analysed. Headache frequency, attack duration, headache severity and headache-related disability before and after treatment initiation with zonisamide were compared. Thirty-three patients were included in the study (average age 43.9 +/- 8.4 years; 23 (70%) with TM and 10 (30%) with EM). The patients had failed an average of 6.2 migraine prophylactic drugs prior to zonisamide. The average zonisamide daily dose was 337.9 +/- 146.3 mg and the average duration of treatment was 186.4 +/- 174.0 days. The average number of days with headache per month was reduced in the entire study population from 20.7 +/- 9.5 before zonisamide treatment to 18.0 +/- 11.3 after its initiation (P = 0.06) [in TM from 24.7 +/- 7.3 to 21.0 +/- 10.7 (P = 0.06); in EM from 11.6 +/- 7.6 to 11.0 +/- 9.7 (P = NS)]. No significant changes in other headache parameters were found. Fourteen patients (42.4%) reported adverse events (AEs), the most common of which was fatigue. Most patients (12/14, 85.7%) rated AEs as mild or moderate. In this group of refractory migraine patients, zonisamide therapy did not result in a statistically significant beneficial effect on headache or on associated symptoms.     

Efficacy of nimodipine in the prophylaxis of migraine

The efficacy of nimodipine in the prophylaxis of migraine was assessed in a double-blind, placebo-controlled, cross-over study carried out on 33 patients, 20 of whom suffered from classic and 13 from common migraine. Four patients dropped out, but not as a result of the side effects of the drug. The duration of drug treatment was 8 weeks. The dosage used was 30 mg four times daily. Nimodipine proved to be better than placebo, the number of migraine attacks and severity of headache showing a significant reduction. The drug was well tolerated and no marked side effects were noted. The results suggest that nimodipine is a useful new prophylactic drug for migraine, but further studies are needed before its final value can be evaluated.     

Efficacy of acupuncture for migraine prophylaxis: a single-blinded, double-dummy, randomized controlled trial

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.     

Anticonvulsants in migraine prophylaxis: a Cochrane review

Several trials have asserted that some anticonvulsant drugs seem to be useful for the prophylaxis of migraine, but systematic reviews are sparse. We independently searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials until 2005, as well as Headache and Cephalalgia through April 2006, for prospective, controlled trials of anticonvulsant drugs. Data were calculated and pooled across studies and expressed as standardized mean differences, odds ratios and numbers-needed-to-treat. Anticonvulsants, considered as a class, reduce migraine frequency by about 1.3 attacks per 28 days compared with placebo, and more than double the number of patients for whom migraine frequency is reduced by ≥ 50% relative to placebo. Sodium valproate/divalproex sodium and topiramate were better than placebo, whereas acetazolamide, clonazepam, lamotrigine and vigabatrin were not; gabapentin, in particular, needs further evaluation. Trials designed with sufficient power to compare different drugs are also necessary.     

Riboflavin prophylaxis in pediatric and adolescent migraine

Migraine is a common disorder in childhood and adolescence. Studies on adults show the effectiveness and tolerability of riboflavin in migraine prevention, while data on children are scarce. This retrospective study reports on our experience of using riboflavin for migraine prophylaxis in 41 pediatric and adolescent patients, who received 200 or 400 mg/day single oral dose of riboflavin for 3, 4 or 6 months. Attack frequency and intensity decreased (P < 0.01) during treatment, and these results were confirmed during the follow-up. A large number of patients (77.1%) reported that abortive drugs were effective for controlling ictal events. During the follow-up, 68.4% of cases had a 50% or greater reduction in frequency of attacks and 21.0% in intensity. Two patients had vomiting and increased appetite, respectively, most likely for causes unrelated to the use of riboflavin. In conclusion, riboflavin seems to be a well-tolerated, effective, and low-cost prophylactic treatment in children and adolescents suffering from migraine.     

Topiramate: a case series study in migraine prophylaxis

We reviewed the electronic records of 74 migraine patients treated with topiramate for more than 6 weeks. Twenty-four patients had episodic migraine and 50 had chronic (transformed) migraine. Most (81%) started treatment at 25 mg per day and reached a dose of 100 mg twice a day (mean dose on the last follow-up visit was 208 mg). The mean headache frequency decreased from 20.6 days to 13.6 days per month (P<0.0001) for all headaches (9.9-5.1 (P<0.0001) and 25.7-17.7 (P<0.001) for episodic migraine and chronic migraine, respectively). The percentage of patients whose headache frequency was reduced by > or =50% was 44.6% for all patients; 58.3 for episodic migraine and 38.0 for chronic migraine. For all patients mean headache severity (10-point scale) was reduced from 6.2 to 4.8 (P<0.0001). Patients on monotherapy (20%) and polytherapy (80%) had similar reductions in headache frequency. Adverse events were usually mild to moderate and were seen in 58.1% (paresthesias in 25%, cognitive difficulties 14.9%). Mean weight loss was 3.1 +/- 4 kg (3.8% of total body weight).     

Telmisartan in migraine prophylaxis: a randomized, placebo-controlled trial

We evaluated telmisartan 80 mg for migraine prophylaxis. Migraine patients ( n  = 95) with three to seven migraine attacks in 3 months were randomized, double-blind to telmisartan or placebo. The primary end-point was the reduction in the number of migraine days (i.e. a day with ≥ 1 h of symptoms) between the 4-week baseline period and the last 4 weeks of the 12-week treatment period. A responder was recorded when there was a symptom reduction of ≥ 50% in these 4-week baseline and treatment periods. The reduction in migraine days was 1.65 with telmisartan and 1.14 with placebo ( P  > 0.05). Post hoc analyses adjusting for baseline and centre showed a 38% reduction in migraine days with telmisartan vs. 15% with placebo ( P  = 0.03), and a borderline significant difference in responders (40% vs. 25%, P  = 0.07). The incidence of adverse events was similar between treatments. This study indicates that telmisartan might be effective in migraine prophylaxis.     

Cyclandelate in the prophylaxis of migraine: a placebo-controlled study

The prophylactic action of cyclandelate was investigated in a multicentre, randomized, placebo-controlled, parallel group study. A 4-week baseline period was followed by a 4-week placebo phase and a 16-week treatment period with either 1600 mg cyclandelate or placebo. Patients (n = 251) with two to six migraine attacks/month were randomized. Neither the primary study endpoint (reduction of migraine days from baseline to the last 28 days) nor most of the secondary endpoints (reduction in the number of migraine attacks, severity or duration of attacks, frequency of autonomic disturbances, medication for treatment of attacks) showed a difference between cyclandelate and placebo. Cyclandelate, however, was superior to placebo in a global impression of efficacy rated by the patients and the treating physicians. Both treatments were well tolerated. In conclusion, cyclandelate was not superior to placebo in the prophylaxis of migraine with regard to parameters usually used in migraine prophylaxis trials.     

尼莫地平治疗急性高血压性脑出血的疗效初步探讨

目的:探讨尼莫地平治疗急性高血压性脑出血的临床疗效。方法:64例急性高血压性脑出血患者被随机分成尼莫地平组30例和对照组34例,2组均接受传统脑出血治疗,尼莫地平组同时静脉滴注尼莫地平,于治疗前及治疗后第7、14天测量脑血肿和脑水肿带体积,于入院时、治疗后第30、90天随访时采用欧州卒中评分量表(ESS)评定神经功能。结果:尼莫地平组较对照组脑血肿、脑水肿体积明显减小,ESS评分明显增高。结论:在高血压性脑出血早期可在传统脑出血治疗的同时使用尼莫地平,以进一步减轻脑水肿、促进脑血肿吸收、改善神经功能。     

Topiramate in migraine progression

Increasing evidence shows that migraine, typically considered as an episodic disease, is a chronic and, in some patients, progressive disorder. Among neuromodulators used for migraine prevention, topiramate has a high level of evidence-based efficacy. Through its wide range of mechanisms of action topiramate increases the activation threshold resulting in neuronal stabilization and thereby reducing cortical neurons hyperexcitability, which is believed to be an important electrophysiological feature underlying the pathogenesis of epilepsy and migraine. Recent studies show that migraineurs have subclinical structural brain changes and persistent alteration of pain perception, in some cases correlated with the duration of the disease and the frequency of attacks that might play a role in the transformation of episodic migraine to chronic forms. An early and prolonged preventive treatment might reduce the risk of such transformation. Recent evidence suggests that topiramate, by reducing migraine frequency and use of acute medication, may prevent the negative progression of migraine. Furthermore, two recently completed multicenter, randomised, placebo-controlled trials have shown that treatment with topiramate 100 mg/day is effective and well tolerated in patients already progressed to chronic migraine and difficult to treat conditions associated with medication-overuse. Topiramate seems to be a preventive treatment, which might be able to act at different levels of the migraine cycle: reduction of frequency in episodic migraine, prevention, and treatment of chronic migraine.     

The dose of propranolol for migraine prophylaxis. Efficacy of low doses

Although propranolol is still the drug of first choice for migraine prophylaxis, the optimal antimigraine dose of this drug is still unknown. The main aim of our study is to clarify this point. Fifty-three patients suffering from severe migraine attacks were given propranolol at low doses, close to or up to 1 mgkg body weight daily, for one month. If the patient responded, then treatment was maintained unchanged for a further two months. If the patient did not respond, propranolol was progressively increased until control was obtained. Thirty-nine (73.5%) patients responded to low doses, and 7 of the 17 patients whose dose had been increased, because of poor or absent response, showed improvement. Five patients did not finish the study because of intolerable side effects, which intensified as the dose was increased. Tolerance was not noticed. In addition to confirming the well-known utility of propranolol in migraine prophylaxis, our results show that low doses are effective in controlling serious migraine bouts in many patients. Fewer than a third of patients will need higher doses in controlling migraine attacks.     

Placebo response in the prophylaxis of migraine: A meta‐analysis

Background: Migraine constitutes a good model for the study of placebo response. It is a well‐defined disease, affects a large population and a great number of clinical trials have been performed, which have given homogeneous outcomes. Aim: The aim of this meta‐analysis is to evaluate the placebo response rate in migraine prophylaxis in all published clinical trials since 1988 and to estimate the influence of study design in response variability. Methods: A computer‐based information search was conducted on the Medline database. The outcomes studied were patients who improved (reduction in migraine attacks of 50% or more); attacks per month, and patients with adverse events. Study design and countries in which the study was carried out were also analysed. The meta‐analysis was computed using the Mantel–Haenszel test. Results: In the final analysis, 32 papers were considered. The pooled estimate of the placebo response (patients who improved) was 21%. The placebo response rates were significantly higher in studies with a parallel design than those in cross‐over studies (p<0.01). This response was also higher in European studies than in those performed in North America (p<0.001). Adverse events occurred in 30% of the patients who took a placebo, and the percentage of patients with adverse events was significantly higher in the North American studies than in those conducted in Europe (p<0.01). Conclusion: These data reinforce the need to consider the placebo effect when ascertaining the true therapeutic effect of any drug, as well as to design any clinical trial in the prophylaxis of migraine.     

Efficacy of intravenous magnesium sulfate in severe migraine attacks

The aim of this open study was to make a preliminary estimate of the efficacy and tolerability of intravenously administered magnesium sulfate (1 g) in comparison to subcutaneously administered sumatriptan in the treatment of severe migraine attacks. The study comprised 22 consecutive patients whose attacks were treated with magnesium sulfate (5 ml of a 20% solution), and the results were compared with those of another group of 14 consecutive patients whose attacks were treated with sumatriptan (6 mg). Immediately before and 10, 20 and 30 minutes after injections, patients reported pain intensity on a verbal 0–10 scale. Pain disappearance or pain relief >50% were considered significant. Efficacy of sumatriptan was superior that of to magnesium sulfate 20 minutes after the injections (p<0.05) and comparable after 30 minutes (magnesium therapy was successful in 68% in comparison to 79% of patients treated with sumatriptan). After only 10 minutes, 3 patients treated with magnesium sulfate were pain free, with the same effect in 5 (22.5%) and 10 (45%) patients after 20 and 30 minutes, respectively. The rate of headache recurrence was low and no major adverse effects were recorded. In conclusion, magnesium sulfate may be a well-tolerated pharmacological alternative for the treatment of severe migraine attacks. Received: 12 January 2001 / Accepted in revised form: 6 July 2001     

Acetazolamide for the prophylaxis of migraine in CADASIL: a preliminary experience

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by NOTCH3 mutations. It is characterized by migraine, with or without aura, ischemic events, psychiatric and cognitive disturbances. There is no approved treatment for migraine prophylaxis in CADASIL, but acetazolamide has been anecdotally reported to be effective. We retrospectively reviewed our database of patients with a genetic diagnosis of CADASIL to identify how many of them were treated with acetazolamide for the prophylaxis of migraine. The efficacy and the tolerability of this treatment were checked looking at the clinic reports. Acetazolamide was prescribed in seven patients; the mean duration of treatment was 6 months, and the daily dose ranged from 125 to 500 mg. Three patients had a total and sustained remission, while in two patients a reduction in attacks and an improvement of the headache intensity were recorded. In one of these, acetazolamide was deliberately taken only during the migraine attack and the beneficial effect started 1 h after administration. In two patients, the drug did not produce any beneficial effect. Mild side effects were recorded in two patients. Our preliminary experience expands previous reports and confirms the possible efficacy of acetazolamide in CADASIL migraine. Based on these data, a randomized controlled trial seems worthy to be carried out to test the efficacy and safety of this drug.     

Frequency of severe attacks in migraine sufferers of the Gazel cohort

The concept of severe migraine was raised to define migraineurs most in need of care and for use in clinical practice. We aimed to measure the frequency of severe attacks in a working sample of 276 migraine sufferers using a diary over a 3-month period. Migraine sufferers recorded each attack's clinical features, the degree of their disability, their use of drugs and the effectiveness of the drugs. Since the definition of severe attack is not standardized, we studied the impact of different definitions on the frequency. The frequency of severe attacks was 0.9% and appeared to be very sensitive to the definitions, ranging between 0.4 and 13%. In France, the extrapolated number of severe attacks is nearly one million out of a total of 115 million. In the migraineurs who had had at least one severe attack, the individual variability of intensity, duration or disability was very high, so the proportion of severe attacks in a given sufferer was low-between 15% and 50%. We conclude that the global concept of severe migraine is not relevant and should be split into two componentssevere attack and severe migraine sufferer. The goals are different, too. Regarding treatment, for example, the severe attack concept is more valid for acute treatment strategies, whereas the severe migraine sufferer concept should be preferred to determine the need for prophylactic treatment. Since much work is being done nowadays to define a rate treatment strategies, definition of the criteria of severe attack and validation of a measurement tool should be a priority.     

A comparative study of magnesium, flunarizine and amitriptyline in the prophylaxis of migraine

Circumstantial evidence points to the possible role of magnesium (Mg⁺²) deficiency in the pathogenesis of migraine and has raised questions about the clinical utility of magnesium as a therapeutic regimen in migraine. This was a prospective, randomized, double-blind, placebo-controlled trial comparing the efficacy and tolerability of 1830 mg magnesium citrate (23 patients), 10 mg flunarizine (22 patients) and 10 amitriptyline (20 patients) in the prophylaxis of migraine diagnosed according to the criteria of the International Headache Society. Patients were evaluated for attack frequency, severity and drug side effects monthly for 3 months. Magnesium, flunarizine and amitriptyline were all superior to placebo (p<0.001) in reducint both attack frequency and severity after the first month. There was no significant difference between the 3 active drugs in reduction of attack frequency and severity. No serious side effects were observed and the frequencies of side effects were not significantly different in all treatment groups. Our results show that oral magnesium is an effective and well tolerated drug in the prophylaxis of migraine and compares well to established drugs like flunarizine and amitriptyline both in effectiveness and occurence of side effects. Magnesium may be an alternative drug in migraine prophylaxis, but more and larger comparative trials are needed to confirm these results. Received: 28 August 2000 / Accepted in revised form: 10 January 2001     

Use of a structured migraine diary improves patient and physician communication about migraine disability and treatment outcomes

Migraine is frequently undertreated, perhaps because impaired communication between patients and physicians underestimate the disability associated with migraine attacks. The purpose of this study was to evaluate the benefits of a structured migraine diary used during a prospective open-label study of triptan-naive patients in Spain for recording information on response to therapy for a pre-study migraine attack and three consecutive migraine attacks, the first and third treated with rizatriptan 10-mg wafer and the second with usual non-triptan therapy. Of 97 patients (83% women; mean age, 39 years) who completed the study, all reported moderate to severe pain, and two-thirds reported severe to total impairment during migraine attacks. At study end, 72% of patients reported that the migraine diary helped communication with their doctor about migraine, and 70% were more or much more satisfied than before the study with level of overall medical care provided by their doctor. Patients who reported the diary to be useful also reported higher overall satisfaction with medical care (p < 0.001). Most of the 22 physicians (91%) reported that the diary enabled them to better communicate with their patients about migraine, and all reported that it enabled them to assess differences in pain intensity and disability across patients. We conclude that a structured migraine diary can be a valuable aid for improving communication between physicians and patients regarding migraine disability and treatment outcomes.     

Cinnarizine in refractory migraine prophylaxis: efficacy and tolerability. A comparison with sodium valproate

This was a double-blind clinical trial designed to assess the efficacy and safety of the cinnarizine (CIN) in patients with migraine who were refractory to propranolol and tricyclic antidepressants in comparison with sodium valproate (SV) to investigate whether CIN could be at least as effective as SV. A total of 125 patients were treated in a treatment period of 12 weeks. All patients had at least one intake of trial medication and 2-week post baseline efficacy observation which all were included in the ITT analysis. Of the 125 subjects treated, 46 discontinued prematurely: 25 from the CIN and 21 from the SV group. The main reasons for premature discontinuation were: lost to follow up (25/46, 63.2%), insufficient response (16/46, 20%), and adverse events (5/46, 12.8%). No statistically significant inter-group differences in the number of discontinuation was observed (p > 0.05). In both groups, number of attacks, intensity, and duration of attacks significantly decreased (p < 0.05). No statistically significant inter-group differences were observed regarding the mean number of attacks, duration, and intensity of migraine attacks for any of the time intervals analysed, except for the mean reduction of third and fourth visits intensity from baseline which were significantly different in two groups (p < 0.05), with the CIN group showing more reduction. Analysis of the number of responders showed that in the CIN group 61.2% subjects were responders, and 63.8% in the SV group. No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall 26 subjects reported one or more adverse events during the study period: 13 subjects in each group. Five subjects discontinued prematurely due to adverse events; two in the CIN group with significant weight gain, and 3 in the SV group with significant weight gain and severe tremor. These results suggest that CIN is an effective and safe prophylactic agent even in severe migraine headache. An erratum to this article can be found at     

Preventive treatment of migraine: an overview

The pharmacologic treatment of migraine may be acute (abortive, symptomatic) or preventive (prophylactic). Most migraine preventive medications were designed to treat other disorders (e.g., propranolol for hypertension, valproate for epilepsy, etc.). Preventive medication is usually given daily for months or years; however, treatment can be episodic, subacute, or chronic. The medications can be divided into two major categories: (i) Alternatives of high efficacy, which include β- blockers , tricyclic antidepressants , and divalproex , and of lower efficacy, which include selective serotonin reuptake inhibitors, calcium channel antagonists, and non-steroidal antiinflammatory drugs and (ii) second-line choices of high efficacy, which include methysergide and monoamine oxidase inhibitors. The choice of preventive treatment depends on the individual drug's efficacy and side effects, the patient's wants, needs, and response to prior treatment, and the presence of any comorbid or coexistent disease.