Double-blind randomized placebo-controlled study of homoeopathic prophylaxis of migraine

Homoeopathic remedies for migraine are widely available over the counter, statutorily offered by the national health service in the UK, and apparently popular with patients. Do they work? Sixty-three outpatients with migraine with or without aura by IHS criteria entered a 4-month randomized placebo-controlled, double-blind parallel-groups trial of individualized homoeopathic prophylaxis, the first month being baseline with all patients on placebo. Three patients (4.8%) dropped out, leaving 30 in each treatment group. There were chance differences in attack frequency and severity between the groups at baseline (attacks were more frequent but less severe in the placebo group). Both groups improved on therapy, but neither to a great extent on the primary outcome measure of attack frequency (verum: -19%; placebo: -16%). Reduction was mostly in mild attacks on placebo, more in moderate and severe attacks on homoeopathy. Few adverse events were reported. Overall, there was no significant benefit over placebo of homoeopathic treatment. The course of change differed between groups, and suggested that improvement reversed in the last month of treatment on placebo. On this evidence we cannot recommend homoeopathy for migraine prophylaxis, but cannot conclude that it is without effect.     

Stabilization treatments of migraine

Pathophysiology and principles for diagnosis of migraine, in particular ways to obtain an accurate history between attacks, are presented in the introduction. Identification of migraine triggers is an extremely important part of migraine therapy. Selected pain-relieving drugs should include primarily simple analgesics and antiemetics, while sumatriptan should be reserved mainly for severe migraine attacks. Pharmacotherapy, psychological and physical therapy are all components of a systemic approach to the treatment of migraine. To discontinue overused medication is the first step in the prevention of migraine. A number of available drugs are able to reduce the frequency and severity of migraine attacks. Several considerations should be evaluated before symptomatic and prophylactic therapies are introduced. Our strategies are based on experience collected during the treatment of 82 patients.     

Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18-64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 10 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.     

Medical treatment of migraine: from mechanisms of action to contraindications

Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).     

Management of children with epiglottitis during transport: analysis of a survey

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 at 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.     

Procarboxypeptidase in rat pancreas. Overall characterization and comparison of the activation processes

In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with 6 mg sumatriptan sc using an autoinjector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated "adequately" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an autoinjector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist.     

Sumatriptan in the acute treatment of migraine without aura: efficacy of 50-mg dose

We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.     

A review of the treatment of primary headaches. Part I: Migraine

Finding the best treatment for a patient's migraine is often a problem in clinical practice since the condition is very common, often debilitating and may prove refractory to therapy. Over recent years, more effective migraine treatments have been found and validated, and the traditional remedies have undergone controlled testing. This article reviews the various therapies available for both the acute treatment and prevention of migraine. Treatments often effective against migraine attacks are: aspirin, analgesics, non steroid anti-inflammatory drugs (NSAIDs), ergot derivatives and sumatriptan. Five main classes of prophylactic drug are currently used: beta-blockers, calcium antagonists, serotonin modulators, NSAIDs and ergot compounds. Biofeedback, one of the most efficacious non-pharmacological preventive treatments of migraine, is also discussed. The variables influencing the choice of acute and preventive treatments, including contraindications and drug availability, are also described in order to provide a practical and up-to-date guide to migraine therapy.     

Cutting the costs of migraine: role of the employee health unit

It is estimated that over 120 million Americans suffer from moderate to severe attacks of migraine characterized by headache and other debilitating symptoms, resulting in impaired functional capacity and diminished quality of life. And, it appears, its prevalence is increasing. Since the prevalence peaks during the ages of 25-55, the prime working years, migraine places a tremendous burden on employers, primarily in the form of lost productivity as well as increased health benefits costs. The fact that migraine is underdiagnosed and undertreated suggests the existence of opportunities for interventions that will reduce that toll. This article focuses on the contributions that employee health units may make to such interventions. In addition to first aid for migraine attacks occurring during working hours, these interventions may include educating occupational health staff, managers, and line supervisors about the management of migraine; identifying migraineurs in the workforce; educating them about their problem and ensuring that they are receiving optimal care; controlling exposures to factors in the workplace that may trigger migraine attacks; and managing disability to minimize loss of productivity. Perhaps most important is encouraging migraineurs to be more aggressive in confronting this problem and empowering them to seek out personal physicians who will guide them to effective treatment and preventive regimens.     

Sumatriptan. An updated review of its use in migraine

Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the injectable form has also shown efficacy in the treatment of cluster headaches. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing resolution or reduction of other symptoms associated with migraine, including nausea, photophobia and phonophobia. Improvements in clinical disability were also significantly greater after sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who received oral or subcutaneous sumatriptan, but most patients responded to a second dose of the drug. Results of comparative trials showed that subcutaneous sumatriptan 6 mg was significantly more effective than either patients' usual antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but the headache recurrence rate was significantly higher after sumatriptan than after this formulation of dihydroergotamine mesylate. Response rates achieved after oral sumatriptan were similar to those reported after treatment with oral naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide. Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads to less loss of workplace productivity than other antimigraine therapies. Several pharmacoeconomic analyses showed that gains in workplace productivity in sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year. Significant improvements from baseline in overall health-related quality-of-life scores were also experienced by sumatriptan recipients. Sumatriptan is generally well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse events with oral sumatriptan. Injection site reactions occur in 10 to 40% of patients receiving the drug subcutaneously. A bitter taste at the back of the mouth occurs frequently after intranasal administration. Serious adverse events occur in about 0.14% of patients with migraine treated with sumatriptan. As the drug is associated with the rare development of cardiovascular effects, it is contraindicated in patients with a history of cardiovascular disease. CONCLUSIONS: Despite its relatively high acquisition cost, reductions in lost workplace productivity experienced by patients treated with sumatriptan may result in savings in the overall cost of migraine to society. Thus, sumatriptan is a useful first- or second-line treatment option for patients with moderate or severe migraine.     

Repeated doses of combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine

The combination of lysine acetylsalicylate and metoclopramide is effective in the treatment of migraine attacks. It was unknown whether repeated doses could improve efficacy. The aim of this open trial was to evaluate the effects of a second, and eventually a third dose of lysine acetylsalicylate and metoclopramide when a first dose of the treatment was ineffective. Patients were asked to take a second dose 2 hours after a first dose when they thought that the first dose was ineffective. They were allowed to take a third dose or their rescue medication 2 hours after the second dose when they judged that the treatment remained ineffective. Two hundred ninety-two patients were included in the study; 262 of the 292 patients treated 517 attacks. Headache relief (reduction in headache severity from grade 3 or 2 to grade 1 or 0) was observed in 54.8% of attacks after one dose, in 48.1% of attacks after a second dose, and in 40.3% of attacks after a third dose. Complete headache relief without recurrence and without use of a rescue medication was reported in 37% of the total attacks. The patients judged their treatment as good or excellent in 78% of attacks treated with one dose, in 41% of those treated with two doses, and in 19% of those treated with three doses. Tolerance, as judged by the patients, was considered good in 92% of treated attacks. Minor side effects occurred in 6% of attacks after a first dose, in 4.5% of attacks after a second dose, in 1.5% of attacks after a third dose, in 2% after unspecified delay, and in 14% overall. In conclusion, the efficacy of lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks can be improved by repeated doses. It is well tolerated.     

Migraine with aura shows gadolinium enhancement which is reversed following prophylactic treatment

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.     

Vertigo and migraine

Vertigo consists of a variety of syndromes and can be due to many etiologies. One of these causes is migraine, which in our experience is often overlooked, although migrainous vertigo is well known in the literature. Vertigo in migraine can occur as aura or during the headache phase, or independent of the attacks as aura without headache. The aim of this retrospective study was to analyze cases with vertigo and migraine: 23 (8%) of 298 patients with migraine examined in a neurological outpatient department also had rotational vertigo. 48% of these patients had vertigo independent from typical migraine headache. Two types of vertigo were found: permanent vertigo, and vertigo with the characteristics of paroxysmal positional vertigo. 57% of the vertiginous attacks lasted hours, 26% even days, and 17% minutes. Most of the patients had several attacks of vertigo, some involving up to 30 episodes. To recognize migraine as a cause of vertigo has therapeutic implications. Most of our patients with vertigo and migraine showed a good response to antimigraine therapy.     

Total 5-hydroxyindoles in blood related to migraine attacks

The total 5-hydroxyindoles (5HI) in whole blood were measured in 20 migraine patients during spontaneous migraine attacks and in headache-free periods. A statistically significant fall in blood 5-HI was found during headache in 17 patients suffering from classical and common migraine. In one patient with complicated migraine no change was found, and in two patients, one with common migraine and one with migraine and associated symptoms, there was a rise in total blood 5-HI during migraine attacks. The results are compared with previous findings in this field, and it is suggested that during migraine attacks there might be a rise in the plasma 5-HI. The possibility of using the 5-HI fall during spontaneous migraine attacks as a simple test for the diagnosis of migraine is discussed.     

Management of primary headache in emergency services of Santos and surrounding towns

OBJECTIVES: Primary headaches are often seen by Clinicians on duty at Emergency Services. We have investigated the treatment of such patients by 43 medical doctors who have been working at Emergency Services in the city of Santos and surrounding towns for many years. RESULTS: We confirmed the high prevalence of primary headaches in Emergency Services. There seem to be diagnosis difficulties concerning differentiating attacks of migraine and tension type headache. We also observed that IV dipirone was the most frequently prescribed treatment for patients with primary headaches in this study. There is no protocol in the literature which recommends IV dipirone for the treatment of migraine attacks or other primary headaches. CONCLUSION: It would be advisable to perform controlled double blind studies in order to verify the advantages of IV dipirone in the treatment of intense attacks primary headaches. We concluded that headache management recycling programs could be of interest for doctors who regularly work at Emergency Services.     

Specific amino acid substitutions in the proline-rich motif of the Rhizobium meliloti ExoP protein result in enhanced production of low-molecular-weight succinoglycan at the expense of high-molecular-weight succinoglycan

A case of a 35-year-old woman with abdominal migraine is presented. For four years she had been suffering from abdominal pains occurring only at night, always between 1 and 3 a.m. The patient always woke with abdominal pains and nausea. Each time she had diarrhoea and vomited and found that this gave her relief from the pain. Sometimes she lost consciousness for 1-2 minutes. After the attack she felt very weak, her legs and feet became numb and she found it difficult to get to sleep. The attacks and the fainting fits increased in frequency until she had several a month. Numerous gastrological examinations did not reveal any deviations from the normal. At the anti- epileptic consulting unit, abdominal epilepsy was excluded (no abnormalities were found in the eeg and CT examinations of the cranium). As a child she had paroxysmal abdominal pains. When the patient was 10 years old, she had an attack lasting one week and though the pain was severe on the left side, appendectomy was performed. Her mother suffers from migraine with very severe head pains. The patient was referred to our consulting unit where she was treated with Pizotifen in doses of 0.5 mg morning and noon and 1 mg in the evening for three months during which time she had no attacks. A few weeks after discontinuing this treatment, the nocturnal attacks again occurred though the pains were not so severe. She was then prescribed Nitrendipine, 5 mg nightly, and the attacks ceased. However, the patient said that she had felt better when taking Pizotifen.     

Light-induced discomfort and pain in migraine

Quantitative thresholds for discomfort and pain with monocular and binocular light stimuli were measured in 67 controls and 67 migraine patients (37 migraine with aura and 30 migraine without aura). Patients were more photophobic during attack than outside attack (p < 0.03), and they were more sensitive to light than controls even between attacks (p < or = 0.0001). We found no differences in light sensitivity between migraine with aura and migraine without aura (p > or = 0.93). Unilateral pain affected light sensitivity on both sides. When asked with a questionnaire, 74% of patients answered that they were sensitive to light outside attack and 100% were sensitive during attack. Pain thresholds were generally lower among sensitive than non-sensitive patients (p = 0.004), indicating some agreement between subjective opinion and objective measurements of photophobia. Photophobia seems to be an intrinsic property of migraineurs. It is increased by migraine pain, but seems to be unrelated to migraine characteristics such as nausea, severity of attacks, pain character and pain laterality.     

Beneficial effects of Helicobacter pylori eradication on migraine

BACKGROUND/AIMS: Migraine is a commonly unilateral throbbing headache, which has been associated with disorders of the vascular tone. Helicobacter pylori, the most relevant cause of gastritis and peptic ulcer, has been recently associated with a typical functional vascular disorder such as primary Raynaud phenomenon. The aim of this study was to assess the prevalence of H. pylori for patients affected by migraine and the effects of H. pylori eradication on migraine symptoms. METHODOLOGY: Two-hundred and twenty-five patients were consecutively enrolled between October 1996 and January 1997. H. pylori was assessed by 13C-urea breath test. Infected subjects were eradicated of the bacterium; frequency, intensity and duration of attacks of migraine were assessed during a 6 month follow-up period. RESULTS: H. pylori was detected in 40% of the patients. Eighty-three percent of the patients who underwent therapy were eradicated. Intensity, duration and frequency of attacks of migraine were significantly reduced in all eradicated patients. CONCLUSIONS: H. pylori is common in subjects with migraine. Bacterium eradication causes a significant decrease in attacks of migraine. The reduction of vasoactive substances produced during infection may be the pathogenetic mechanism underlying the phenomenon.     

Response to prophylactic treatment of benign headache in children

INTRODUCTION: Common childhood headaches seldom require prophylactic treatment which, nevertheless, is quite often unsatisfactory. OBJECTIVE: To study drug and non-drug related factors that may influence the therapeutic response. MATERIAL AND METHODS: A four-month follow-up study of all patients attended during a year at the neuropediatric, outpatient hospital-based clinic, with > or = 2 monthly migraine without aura attacks, > or = 10 tension-type headaches, or both types of headaches. Patients were randomized to be treated on an open basis, placebo controlled, with flunarizine or piracetam. Headache frequency was evaluated according to treatment and patients' basal characteristics. RESULTS: 98 patients studied (56 migraine without aura, 24 tension-type headache, 18 mixed). 33% dropped out; they were school underachievers more frequently than those that completed the protocol. Of those completing the protocol and treated with placebo as the first choice of therapy, 27% reported total remission of symptomatology; those not remitting with placebo were high achievers at school significatively more frequently. At the end of the trial, 43% of the initially randomized patients still complained of headaches, regardless of treatment, showing a seasonal relationship. CONCLUSIONS: Prophylaxis of benign childhood headaches is needed in less than half of those reporting a high headache frequency; school achievement should be taken into consideration as another clue to compliance and headache persistence. On a short-term basis only the seasonal influence and the placebo effect can be held responsible for amelioration of symptomatology.