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Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo–controlled, dose–ranging trials. We conducted a randomised, doubleblind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double–blind treatment phase. Five hundred and seventy–five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles. [ABSTRACT FROM AUTHOR]

Subcutaneous injection of sumatriptan is an effective treatment for attacks of cluster headache with a short onset of action. This open, randomized study evaluates whether sumatriptan nasal spray at its highest commercially available dose (20 mg/dose) is equally effective. In 26 patients, four consecutive attacks were treated alternately with nasal spray and subcutaneous injection. Treatment was given within 5 min of onset of pain, and the time interval for the start and completeness of pain relief, provided these occurred within 15 min of administration, were recorded by the patient. After completion of the study, the patients were also asked to indicate which treatment they preferred, based on efficacy, side effects, and handling of the preparation. Forty-nine of the 52 treatments with injection resulted in complete relief of pain within 15 min, with a mean of 9.6 min. The remaining three attacks were reduced by a mean of 86.7% at 15 min. Only 7 of the 52 treatments with nasal spray in the nostril ipsilateral to pain resulted in complete relief within this time period, with a mean of 13.0 min. In 18 of these treatments pain was reduced by a mean of 42.2% at 15 min, whereas no effect on pain was obtained at this time in the remaining 27 treatments. The effect was almost identical when the nasal spray was administered in the nostril on the non-painful side. As an overall judgement, only 2 of the 26 patients preferred nasal spray to injection. We conclude that sumatriptan nasal spray 20 mg/dose is less effective than subcutaneous injection in relieving pain in the great majority of cluster headache sufferers. [ABSTRACT FROM AUTHOR]

A long-term clinical trial of acyclovir, 800 mg tid, as a therapeutic agent in multiple sclerosis (MS) is in progress. In three patients paired serum and cerebrospinal fluid (CSF) specimens were sampled after one, four, eight and twelve months of continuous treatment These samples were collected 1·5 h before or 1·5 h after an oral dose. Acyclovir concentrations were assessed by radioimmunoassay. In the CSF, the acyclovir concentration was relatively stable, with a mean of 0-83 μM, while the serum acyclovir concentration was variable with mean peak and trough concentrations of 4·08 and 2·47 μM, respectively. In two other MS patients the acyclovir concentration time profile in serum and CSF was studied at steady state during the 8 h dose interval. In this study the acyclovir concentration in the CSF was only slightly affected by the fluctuations in serum and the acyclovir CSF/acyclovir serum ratio was apparently not influenced by the blood-brain barrier function. We found no indication of an accumulation of acyclovir in cerebrospinal fluid after one to twelve months of oral treatment. [ABSTRACT FROM PUBLISHER]

The aim of the study was to evaluate the prevalence of subjective perception of dry mouth in an adult population and to determine the prevalence of pharmacotherapy in this population. An additional aim was to assess a possible co-morbidity between symptoms of dry mouth and continuing pharmacotherapy. Four-thousand-two-hundred persons were selected at random from the national census register of the adult population of the southern part of the province of Halland, Sweden. The sample was stratified according to age and sex, and 300 men and an equal number of women aged 20, 30, 40, 50, 60, 70 and 80, were included. A newly developed questionnaire was mailed to each individual. In addition to questions about subjective perception of dry mouth, the subjects were asked to report on present diseases and continuing pharmacotherapy. Three-thousand-three-hundred and thirteen (80.5%) evaluable questionnaires were returned. The estimated prevalence of xerostomia in the population was 21.3% and 27.3% for men and women, respectively. This difference between the sexes was statistically significant. In non-medicated subjects, women tended to report a higher prevalence of xerostomia compared with men, 18.8% vs. 14.6%, and also among medicated subjects the estimated prevalence of dry mouth was higher for women than for men, 32.5% vs. 28.4%. There was a strong association between xerostomia and increasing age and also between xerostomia and continuing pharmacotherapy. The average prevalence of dry mouth among medicated and non-medicated subjects was 32.1% and 16.9%, respectively, the difference being statistically significant. There was also a strong association between xerostomia and the number of medications. In a logistic regression, the probability of reporting mouth dryness was significantly greater in older subjects and in women, and the probability increased with the number of medications taken. [ABSTRACT FROM AUTHOR]

Adrenaline is the drug of choice for management of the anaphylactic reaction. The objective of this study was to compare systemic absorption of adrenaline after administration by different routes to healthy volunteers. Ten puffs (1.5 mg as adrenaline base) with 10-15 s intervals between them followed 2 h later by 20 puffs (3 mg) of adrenaline from a pressurized aerosol (Medihaler-Epi, 3M Riker, 14.0 mg/ml adrenaline acid tartrate) were sprayed into the cheek pouch or inhaled through the mouth or the nostrils. Adrenaline was also administered to the eyes by giving 2 drops (1 mg) of Isopto-Epinal (Alcon, 10 mg &time; ml-1). Finally, 0.5 ml (0.5 mg) of adrenaline was given subcutaneously in the upper arm of the same individuals. The systemic absorption was determined by measuring plasma adrenaline levels and effects on blood pressure, heart rate and finger tremor before and 5, 15, 30, 60, 90, and 120 min after adrenaline administration. Adrenaline given as eye-drops did not have any significant effect on these parameters. Subcutaneously administered adrenaline caused within 5 min a significant increase of plasma adrenaline level (from 1.0 ± 0.2 to a peak of 6.5 ±1.2 nM) which gradually decreased during 2 h. This mode of adrenaline administration increased the systolic blood pressure by a maximum of 11 ± 3.5 mmHg, heart rate by 9 ± 2.2 beats &time; min-1', tremor ratio by 4 ± 0.6 and reduced the diastolic blood pressure by 18 ± 4.7 mmHg. The cardiovascular effects were approximately maximum 15 min after administration and lasted almost 90 min. After 10 inhalations through the mouth no significant effects were seen, whereas after 20 inhalations the plasma adrenaline level increased significantly (from 1.1 ± 0.2 to a peak of 2.4 ± 0.6 nM). The effects on blood pressure, heart rate and finger tremor ratio were more short-lived than those caused by subcutaneously administered adrenaline. The effects of nasal inhalation of adrenaline were similar but more long-lasting when compared to oral inhalation. Conclusion. Inhaled adrenaline gives rapid systemic absorption but this is less pronounced and more short-lasting than with subcutaneous adrenaline. Apart from being easier for the patient to use, the inhaled route of adrenaline administration also appears to be cardiovascularly safe within a wide dose range. It is therefore suggested that patients known to be hypersensitive should be equipped with Medihaler Adrenaline for emergencies as a complement to subcutaneous adrenaline. Further, the recommended dose of this inhaler in the treatment of acute upper airway hyperreactive conditions should be increased to 10-20 inhalations, which can be repeated if necessary. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the effects of a β 1-selective (atenolol 50 mg q.d.) and a non-selective (propranolol 80 mg b.i.d.) β-adrenoceptor antagonist on human stimulated parotid and submandibular-sublingual (SM-SL) gland secretion. A randomized double-blind, placebo-controlled cross-over ("Latin square") design was used in 19 healthy male volunteers. Stimulated parotid and SM-SL saliva were sampled immediately before and 7 days after the start of each treatment period. Stimulation of salivary secretion was achieved by use of a 3% citric acid solution. Plasma concentrations of propranolol and atenolol were determined from blood samples. The salivary secretion of both glands was assessed for flow rate, amylase, lysozyme, and salivary peroxidase activity and for concentrations of total protein, hexosamine, sialic acid, Ca2+, Cl-, K+, Mg2+, Na+, and PO43-. In both parotid and SM-SL secretions, the total protein and phosphate concentrations and amylase activity were significantly decreased during the two active treatment periods. In SM-SL gland secretion, there were significant changes in potassium and calcium concentrations during active treatment as compared with baseline, with potassium showing a decreased and calcium an increased concentration. During atenolol treatment, salivary peroxidase activity decreased significantly in SM-SL secretion. In parotid secretion, the hexosamine/total protein ratio decreased and the sialic acid/hexosamine ratio increased during atenolol treatment, which may indicate an effect on protein synthesis. No significant effects on salivary secretion rates were disclosed. [ABSTRACT FROM AUTHOR]

Presents several guidelines on the controlled trial of drugs used for treating migraines. Selection of patients; Role of health-related quality of life measures; Checklists for acute and prophylactic treatments.

Abstract Background Topiramate is approved for the prophylaxis (prevention) of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ) scores versus placebo (p < 0.001). The MSQ measures how much migraine limits/interrupts daily performance. Pooled analyses of pivotal trial data were conducted to further assess how topiramate 100 mg/d affects daily activities and patient functioning. Methods Mean MSQ and Medical Outcome Study Short Form 36 (SF-36) change scores (baseline to each double-blind assessment point) were calculated for pooled intent-to-treat (ITT) patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: < 50% responders or ≥ 50% responders. Between-group differences were assessed using analysis of covariance. Results Of 756 patients (mean age 39.8 years, 86% female), 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p < 0.001 [weeks 16 and 26] for role prevention; p < 0.001 for role restriction and emotional function [all time points]). Topiramate 100 mg/d significantly improved SF-36 physical component scores (PCS) throughout the double-blind phase versus placebo (p < 0.001, all time points) and significantly improved mental component scores (MCS) at week 26 (p = 0.043). The greatest topiramate-associated improvements on SF-36 subscales were seen for bodily pain and general health perceptions (p < 0.05; weeks 8, 16, and 26), and physical functioning, vitality, role-physical, and social functioning (p < 0.05; weeks 16 and 26). Significantly greater improvements in all three MSQ domains, as well as the PCS and MCS of SF-36, were observed for ≥ 50% responders versus < 50% responders (p < 0.001). Significantly greater percentages of topiramate-treated patients were ≥ 50% responders versus placebo (46% versus 23%; p < 0.001). Conclusion Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a ≥ 50% migraine frequency reduction.

Presents author's view on introduction of serotonin 5-HT[subIB/ID] agonists in clinical practice for the treatment of patients with migraine. Effect of the drug almotriptan on migraine headache; Tolerance and clinical safety of almotriptan usage.

Presents information on a study which assessed and compared health-related quality of life in headache patients, using the SF-36 generic questionnaire. Association of migraine with other illnesses.

The β-adrenoceptor mediated effects on ventilatory capacity, forced expiratory volume in one second (FEV), forced ventilatory capacity (FVC), heart rate, and skeletal muscle tremor of a new controlled-release (CR) formulation of metoprolol, 100 mg and 200 mg, and of atenolol tablets, 100 mg, were studied in eight asthmatic patients. The effects of single-dose treatment, including placebo as reference, were studied in a randomized, double-blind, cross-over design. Starting 2 h after drug intake, four intravenous infusions containing increasing doses of terbutaline were given at 30-min intervals, followed by three doses of terbutaline inhalations. Maximum plasma concentrations for both metoprolol and atenolol were achieved within the study period. The FEV measurements after terbutaline infusions and inhalations were significantly lower after atenolol than after either dose of metoprolol CR. This indicates less blockade of β-adrenoceptors with metoprolol CR than with atenolol at maximum plasma concentrations. The terbutaline-induced skeletal muscle tremor and increase in heart rate were less after atenolol than after either dose of metoprolol CR, also suggesting less interaction of metoprolol CR with β-receptors. Thus, the new CR formulation of metoprolol caused fewer adverse effects on β-adrenoceptor mediated bronchodilatation than a clinically equivalent dose of atenolol. [ABSTRACT FROM AUTHOR]

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypothesis. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D2 receptor antagonist metoclopramide. This drug also has 5HT3 receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D2 receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT4 receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options. [ABSTRACT FROM AUTHOR]

Linde M, Fjell A, Carlsson J&Dahlöf C. Role of the needlingper sein acupuncture as prophylaxis for menstrually related migraine: a randomized placebo-controlled study. Cephalalgia 2004. London. ISSN 0333-1024The objectives were to introduce a new method for controlled trials of acupuncture in the field of headache research and to examine the role of needlingper se. Women with menstrually related migraine were randomized to three months of treatment with verum or placebo needles. Three standard size casts were moulded to secure the placebo needles in the head. No significant differences were found between the verum group (n = 15) and the placebo group (n = 13) during treatment or follow up three and six months later, either in the attack frequency or in the number of days per month with migraine, headache intensity or drug-use. The casts held the needles exactly in place despite movements of the head, and are validated as practical, hygienic and extremely durable. This method is satisfactory for controlled studies of acupuncture in headache. It is possible that the positive results in earlier clinical trials on acupuncture in migraine are attributable to other mechanisms than needling of subcutaneous tissue. [ABSTRACT FROM AUTHOR]

Migraineurs (94F, 24M) with previous experience of subcutaneous sumatriptan and/or sumatriptan tablets were asked their opinion on sumatriptan nasal spray treatment particularly with respect to onset of action, total efficacy, tolerability, and user friendliness. The information was obtained by means of a self-administered questionnaire handed out at the time of prescription of the nasal spray. The results are based on the patients' cumulative experience of having treated at least two migraine attacks with the spray (20 mg). Sumatriptan nasal spray (20 mg) was perceived to have a faster onset of action and, with the exception of a bad taste, to have a better tolerability than the tablets. Compared with subcutaneous sumatriptan, the nasal spray was claimed to be less effective in reducing symptoms of migraine attacks but to cause fewer adverse events. A bitter taste was the most commonly reported side effect of sumatriptan nasal spray--reported by 68% (80 out of 118) of the migraineurs. The user friendliness of sumatriptan nasal spray was rated better than that of subcutaneous sumatriptan and/or sumatriptan tablets. The overall impression of sumatriptan nasal spray was reported to be better or equal to that of the tablet and the injection by 57% and 46%, respectively. It is concluded that the results obtained in clinical practice are very much in line with those obtained in controlled clinical trials. The overall impression of sumatriptan nasal spray is that it is user friendly and useful in the acute treatment of migraine attacks of moderate intensity. [ABSTRACT FROM AUTHOR]

Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n = 46) and 1.4 mg (n = 39). Efficacy, tolerability and safety of each dose were compared with those of placebo (n = 41). At 2 h after injection, headache was absent or mild in 83% and 82% of patients receiving alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p < or = 0.002). Complete relief from headache was achieved in 72% (1.4 mg). Time to onset of relief decreased with increasing alniditan dose, and there was a dose-dependent reduction in headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and headache recurred within 24 h in only 16% of the patients who initially responded to alniditan 1.4 mg, significantly less than for placebo (p = 0.018). Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that alniditan 1.4 mg sc may have advantages over sumatriptan 6 mg sc in providing complete relief from acute migraine headache, and may be associated with fewer headache recurrences within 24 h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine. [ABSTRACT FROM AUTHOR]

Premise: Ethical considerations are made when an experiment is planned and take a regulatory system of moral principles into account., Discussion: Ethical considerations should first and foremost be made in order to protect the individual subject/animal from being exposed to any unethical and perhaps even illegal intervention and to ensure that the experimental conditions used are appropriate., Summary: The main role of research ethics committees is to assess the scientific and ethical aspects of submitted protocols and follow up the trial until its closure.

The 5-hydroxytryptamine (5-HT) receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5-HT(1B) , 5-HT(1D) , and 5-HT(1F) receptors. Ergotamine, dihydroergotamine, and methysergide, as well as the "triptan" sumatriptan, are all agonists for these receptors. The receptor profile and degree of selectivity of these four drugs differ, which is reflected by their side effects that limit their use in the acute and prophylactic treatment of migraine. The acute antimigraine efficacy of these remedies is very much dependent on the formulation used where, in general, parenteral formulations are more effective in reliving the symptoms of a migraine attack., (© 2012 American Headache Society.)

Methods: Four hundred and sixty-one adult subjects with migraine were randomised to one of five treatments, the oral antagonist at the calcitonin gene-related peptide (CGRP) receptor BI 44370 TA (50 mg, 200 mg, 400 mg), active comparator eletriptan 40 mg or placebo. The analysis included 341 subjects who took study medication., Results: The primary endpoint, pain-free after two hours, was reached by significantly more subjects in the BI 44370 TA 400 mg (20/73 = 27.4%) and eletriptan 40 mg (24/69 = 34.8%) groups compared to placebo (6/70 = 8.6%, p = .0016), but not by subjects in the BI 44370 TA 200 mg group (14/65 = 21.5%). The effect of 50 mg BI 44370 TA (5/64 = 7.8%) was similar to that of placebo. Analysis of secondary endpoints supported the conclusion from the primary analysis. The frequency of adverse events was low in all groups., Conclusion: Efficacy of BI 44370 TA was shown in a dose-dependent manner in the treatment of acute migraine attacks.

Background: Topiramate is approved for the prophylaxis (prevention) of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ) scores versus placebo (p < 0.001). The MSQ measures how much migraine limits/interrupts daily performance. Pooled analyses of pivotal trial data were conducted to further assess how topiramate 100 mg/d affects daily activities and patient functioning., Methods: Mean MSQ and Medical Outcome Study Short Form 36 (SF-36) change scores (baseline to each double-blind assessment point) were calculated for pooled intent-to-treat (ITT) patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: < 50% responders or >or= 50% responders. Between-group differences were assessed using analysis of covariance., Results: Of 756 patients (mean age 39.8 years, 86% female), 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p < 0.001 [weeks 16 and 26] for role prevention; p < 0.001 for role restriction and emotional function [all time points]). Topiramate 100 mg/d significantly improved SF-36 physical component scores (PCS) throughout the double-blind phase versus placebo (p < 0.001, all time points) and significantly improved mental component scores (MCS) at week 26 (p = 0.043). The greatest topiramate-associated improvements on SF-36 subscales were seen for bodily pain and general health perceptions (p < 0.05; weeks 8, 16, and 26), and physical functioning, vitality, role-physical, and social functioning (p < 0.05; weeks 16 and 26). Significantly greater improvements in all three MSQ domains, as well as the PCS and MCS of SF-36, were observed for >or= 50% responders versus < 50% responders (p < 0.001). Significantly greater percentages of topiramate-treated patients were >or= 50% responders versus placebo (46% versus 23%; p < 0.001)., Conclusion: Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a >or= 50% migraine frequency reduction.