Naproxen Sodium in Menstrual Migraine Prophylaxis: A Double-Blind Placebo Controlled Study

In this study, the efficacy of Naproxen sodium (Nxs) in the prophylaxis of Menstrual Migraine (MM) was tested, versus Placebo (PL). Forty women suffering from MM were admitted to a double-blind treatment protocol with Nxs 550 mg twice each day by mouth or Placebo (PL), for 3 months; in the next 3 months all the women were treated with the active drug in an open study. The headache intensity and duration, as well as the number of days of headache and the analgesic consumption, were significantly reduced with Nxs compared to PL. The efficacy of Nxs, shown also in improving premenstrual pain, and its good tolerability, support the use of this drug in the prophylactic therapy of MM.     

A Comparative Study of Naproxen Sodium, Pizotyline and Placebo in Migraine Prophylaxis

SYNOPSIS
318 patients satisfying the Ad Hoc Committee's criteria for common or classical migraine were entered into an 8 week single-blind placebo recording phase to establish, by diary cards, the frequency and severity of their attacks. 176 patients completed this and had records indicating 4–8 episodes in the 8 week period, with sufficient severity to reduce activity and/or work; these patients wore randomized by a predetermined code, into three double-blinded groups: naproxen sodium 550 mg bid (60 patients), pizotyline 0.5 mg tid (59 patients), or placebo (57 patients). The patients wore followed at monthly intervals for 12 weeks, with 25 dropping out (3 on naproxen sodium, and 2 each on pizotyline and placebo because of "side effects;" the remaining 18 because of noncompliance or reasons unrelated to therapy). Approximately 25% of patients in each of the 3 groups complained of side effects.
Statistical analysis showed that both naproxen sodium and pizotyline were better than placebo, and of overall equivalent (i.e. equal) efficacy in the prophylaxis of migraine. In some respects, naproxen sodium was slightly more effective than pizotyline in the first month of treatment.     

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

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

苯噻啶、心得安防治偏头痛的作用机制

目的:探讨苯噻啶、心得安防治偏头痛的作用机制。方法:SD大鼠50只随机分为对照组、生理盐水(NS)组、模型组、苯噻啶组和心得安组。模型组、苯噻啶组和心得安组复制大鼠偏头痛模型,第2次造模后苯噻啶组和心得安组分别给予药物干预,第5次造模后测定颈静脉血CGRP含量和脑干及三叉神经节α-CGRP mRNA的表达量,同时观察大鼠的行为学变化。结果:大鼠行为学观察显示,与模型组相比,苯噻啶组、心得安组对硝酸甘油的耐受性增强;各组间颈静脉血CGRP含量无显著性差异(P>0.05);③苯噻啶组、心得安组大鼠脑干及三叉神经节α-CGRP mRNA表达量明显低于其他组(P<0.05)。结论:苯噻啶、心得安预防偏头痛发作可能与抑制脑干及三叉神经节α-CGRP mRNA表达有关。     

Placebo, 1-Isopropylnoradrenochrome-5-Monosemicarbazono and Pizotifen in Migraine Prophylaxis

SYNOPSIS
A new agent to be used in the prophylaxis of migraine has been developed. In addition to its antiserotonin effect it reduces vascular permeability. This preparation, 1-isopropyl-3-hydroxy-5-semicarbazono-6-oxo-2.3.5.6-tetrahydroindol, was compared to pizotifen and to placebo by double-blind cross-over design. The doses were 15 mg respectively. 34 patients with severe and chronic migraine completed the study. The effects did not differ very much from each other. Pizotifen seemed to be more effective, but the semicarbozone derivative caused fewer side-effects. 14 patients reported no benefit from either preparation.     

Single-dose Pizotifen, 1.5 mg Nocte: A New Approach in the Prophylaxis of Migraine

SYNOPSIS
Seventeen patients have taken part in a double-blind, controlled, randomized, cross-over trial, completing four months, two months on each arm of the trial, in which pizotifen 0.5 mg t.d.s. has been compared with 1.5 pizotifen at night. Sixteen patients improved significantly. No significant difference was noted between patients on 0.5 mg t.d.s. compared with 1.5 mg nocte but there was a trend to suggest that initially patients may respond better to the t.d.s. dosage but then maintenance would be more easily carried out on a once nightly regime of pizotifen 1.5 mg nocte. Weight gain appeared to be related to the t.d.s. dosage regime and if this finding is confirmed in subsequent studies then the single dosage at night would certainly be preferable to a t.d.s. dosage regime. We confirm previous studies which show that pizotifen is extremely useful in the prophylaxis of migraine.     

Aborting a Migraine Attack: Naproxen Sodium v Ergotamine plus Caffeine

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

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

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

Disposition of Naproxen After Oral Administration During and Between Migraine Attacks

SYNOPSIS
Naproxen is an anti-inflammatory drug widely used in the management of pain and in the treatment of migraine and headache. As gastrointestinal disturbances are a common feature of migraine, the aim of this study was to evaluate the absorption and the efficacy of naproxen administered during migraine attacks. Ten patients were treated with 500 mg of a soluble form of naproxen during and between migraine attacks. Clinical parameters and drug plasma levels were recorded st scheduled times. Pain reduction, from severe to mild was evident by 6.5 ± 3.4 hours and the total pain score showed a reduction from 2 hours onwards. Pharmacokinetic data showed a slight delay in drug absorption during attacks (absorption half-life and time of maximum drug concentration were increased during attacks), but overall bioavailability of naproxen, as reflected by area under the curve (AUC) and maximum plasma drug concentration were unchanged. Since pain relief was reported, it may be concluded that delayed absorption has little or no influence on the therapeutic effect of naproxen in migraine attacks in fasting patients.     

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

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

Metoprolol in the Prophylaxis of Migraine: Parallel-Groups Comparison withPlacebo and Dose-Ranging Follow-Up

SYNOPSIS
88 patients in need of prophylactic treatment for classical, common or mixed migraine of at least 2years' duration were admitted to a double-blind placebo-controlled trial of the beta1-selective adrenoceptorblocker, metoprolol. All patients initially took placebo for 1 month, during which 29 were excludedprincipally because of failure to reattend or placebo-response making active treatment unnecessary. Theremaining 59 patients were randomised to continued placebo or metoprolol 50 mg b.i.d. for 2 months.Patients after this time subjectively categorizing their responses as less than optimal changed,double-blindly, from placebo to metoprolol 50 mg b.i.d., or from metoprolol 50 mg b.i.d. to 100 mg b.i.d., fora further follow-up period of up to 3 months.
Placebo response was 40% overall, and often occurred after the first month. In the first double-blindcomparative period metoprolol reduced attack frequency significantly, and more than placebo. Severity ofattacks still occurring was not altered by either treatment. Other measures of illness were alteredconsistently with these principal findings. Consistent improvements also were seen in patients switchingfrom initial placebo therapy to metoprolol 50 mg b.i.d. for the further follow-up period, and those changingto the higher dose of metoprolol showed statistically significant further improvements, and clinicallyimportant improvements overall. Side-effects were minor and reversible.
This study gives supportive evidence of the value of metoprolol in preventing migraine attacks andsuggests that individual dosage titration can substantially enhance its efficacy. Side-effects do notsignificantly impede its use and other evidence suggests that beta1-selective blockers are to be preferredover non-selective in migraine therapy.     

Abortive Migraine Therapy With Oral Naproxen Sodium Plus Metoclopramide Plus Ergotamine Tartrate With Caffeine

The oral tablet combination, (550 mgs. of naproxen sodium plus 10 mgs. of metoclopramide plus 1 mg. of ergotamine tartrate plus 100 mgs. of caffeine), was retrospectively studied in 63 patients who used it to abort migraine headaches. On the average, 84% of the headaches were totally aborted; minor side effects occurred in 40% of the patients, and 87% of the patients considered the combination superior to all prior treatments.     

Behavioral Response to Headache: A Comparison Between Migraine and Tension-type Headache

OBJECTIVE: To compare patients with migraine and tension-type headache in their behavior during the attacks and the maneuvers used to relieve the pain. BACKGROUND: Patients with headache often perform nonpharmacological measures to relieve the pain, but it is not known if these behaviors vary with the diagnosis, clinical features, and pathogenesis. METHODS: One hundred consecutive patients with either migraine (n = 72 ) or tension-type headache (n = 28) were questioned (including the use of a checklist) concerning their usual behavior during the attacks and nonpharmacological maneuvers performed to relieve the pain. The results of the two types of headache were compared. RESULTS: Patients with migraine tended to perform more maneuvers than individuals with tension-type headache (mean, 6.2 versus 3). These maneuvers included pressing and applying cold stimuli to the painful site, trying to sleep, changing posture, sitting or reclining in bed (using more pillows than usual to lay down), isolating themselves, using symptomatic medication, inducing vomiting, changing diet, and becoming immobile during the attacks. The only measure predominantly reported by patients with tension-type headache was scalp massage. However, the benefit derived from these measures was not significantly different between the two groups (except for a significantly better response to isolation, local pressure, local cold stimulation, and symptomatic medication in migraineurs). CONCLUSIONS: The behavior of patients during headache attacks varies with the diagnosis. Measures that do not always result in pain relief are performed to prevent its worsening or to improve associated symptoms. These behavioral differences may be due to the different pathogenesis of the attacks or to different styles of dealing with the pain. They can also aid the differential diagnosis between headaches in doubtful cases.     

Fluoxetine Prophylaxis of Migraine

Many patients with severe migraine remain refractory to the current treatment regimens or cannot tolerate the side effects. Since current research implicates serotonin dysregulation in migraine pathogenesis, we investigated in a double blind, placebo controlled study the prophylactic effect of the serotonergic drug fluoxetine. Sixteen subjects were randomly assigned to 8 week fluoxetine treatment and 16 to the placebo group; nine subjects in each group completed the study. Migraine headache scores were obtained for two weeks prior to commencement of treatment, and then for each successive two week period. Zung depression scores were obtained before and after completion of the study. Fluoxetine caused significant reduction in headache scores starting with weeks 3-4 of treatment; there was no significant change with placebo. Depression scores did not differ between groups before treatment, and did not significantly change with either treatment. Fluoxetine appears to be a safe and effective drug for migraine prophylaxis, and deserves further therapeutic trials with larger groups for longer periods of time.     

Prophylaxis of Migraine in Children

SYNOPSIS
About 4 percent of school children suffer from migraine. To prevent attacks it is important to inform the child, the parents and the teachers about the nature of migraine, to prescribe a sound rhythm for the child and to try to remove the attack-provoking factors. It is not always necessary to use prophylactic therapy for migraine in childhood. However, if the attacks are severe and occur three or four times a month then the use of prophylactic drugs is worthwhile. In a pilot study cyproheptadine was given to 19 children aged 6 to 16 years with good effect. Pizotifen was also tried and gave the same good result. Thirty-two school children aged 7 to 16 years were admitted to a double-blind, single crossover propranolol vs. placebo study. The result was good, and side effects of these three drugs were benign.     

Migraine Disability Awareness Campaign in Asia: Migraine Assessment for Prophylaxis

Objectives.— This study aimed to survey the headache diagnoses and consequences among outpatients attending neurological services in 8 Asian countries. Methods.— This survey recruited patients who consulted neurologists for the first time with the chief complaint of headache. Patients suffering from headaches for 15 or more days per month were excluded. Patients answered a self‐administered questionnaire, and their physicians independently completed a separate questionnaire. In this study, the migraine diagnosis given by the neurologists was used for analysis. The headache symptoms collected in the physician questionnaire were based on the diagnostic criteria of migraine proposed by the International Classification of Headache Disorders, second edition (ICHD‐2). Results.— A total of 2782 patients (72% females; mean age 38.1 ± 15.1 years) finished the study. Of them, 66.6% of patients were diagnosed by the neurologists to have migraine, ranging from 50.9% to 85.8% across different countries. Taken as a group, 41.4% of those patients diagnosed with migraine had not been previously diagnosed to have migraine prior to this consultation. On average, patients with migraine had 4.9 severe headaches per month with 65% of patients missing school, work, or household chores. Most (87.5%) patients with migraine took medications for acute treatment. Thirty‐six percent of the patients had at least one emergency room consultation within one year. Only 29.2% were on prophylactic medications. Neurologists recommended pharmacological prophylaxis in 68.2% of patients not on preventive treatment. In comparison, migraine prevalence was the highest with ICHD‐2 “any migraine” (ie, migraine with or without migraine and probable migraine) (73.3%) followed by neurologist‐diagnosed migraine (66.6%) and ICHD‐2 “strict migraine” (ie, migraine with or without aura only) (51.3%). About 88.6% patients with neurologist‐diagnosed migraine fulfilled ICHD‐2 any migraine but only 67.1% fulfilled the criteria of ICHD‐2 strict migraine. Conclusions.— Migraine is the most common headache diagnosis in neurological services in Asia. The prevalence of migraine was higher in countries with higher referral rates of patients to neurological services. Migraine remains under‐diagnosed and under‐treated in this region even though a high disability was found in patients with migraine. Probable migraine was adopted into the migraine diagnostic spectrum by neurologists in this study.