Peter Wessely

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 1 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.

Prospective analysis of factors related to migraine attacks: the PAMINA study.

Migraine is related to numerous factors such as hormones, stress or nutrition, but information about their actual importance is limited. Therefore, we analysed prospectively a wide spectrum of factors related to headache in migraineurs. We examined 327 migraineurs recruited via newspapers who kept a comprehensive diary for 3 months. Statistical analysis comprising 28 325 patient days and 116 dichotomous variables was based on the interval between two successive headache attacks. We calculated univariate Cox regression analyses and included covariables with a P-value of <0.05 in two stepwise multivariate Cox regression analyses, the first accounting for a correlation of the event times within a subject, the second stratified by the number of headache-free intervals. We performed similar analyses for the occurrence of migraine attacks and for the persistence of headache and migraine. Menstruation had the most prominent effect, increasing the hazard of occurrence or persistence of headache and migraine by up to 96%. All other factors changed the hazard by <35%. The two days before menstruation and muscle tension in the neck, psychic tension, tiredness, noise and odours on days before headache onset increased the hazard of headache or migraine, whereas days off, a divorced marriage, relaxation after stress, and consumption of beer decreased the hazard. In addition, three meteorological factors increased and two others decreased the hazard. In conclusion, menstruation is most important in increasing the risk of occurrence and persistence of headache and migraine. Other factors increase the risk less markedly or decrease the risk.

Longterm Prognosis of Analgesic Withdrawal in Patients with Drug‐Induced Headaches

SYNOPSIS

Long-Term Outcome of Patients with Headache and Drug Abuse after Inpatient Withdrawal: Five-Year Follow-Up

Thirty-eight patients with “chronic daily” headache and ergotamine and/or analgesics abuse according to the criteria proposed by the international Headache Society were re-investigated 5 years after inpatient drug withdrawal. At the end of the observation period, 19 patients (50.0%) had their headaches on only 8 days per month or less, 18 patients (47.4%) were free of symptoms or had only mild headaches. A close correlation was found between the frequency of headache and the duration of drug abuse, as well as between the intensity of headache and the number of tablets taken per month. Frequency and intensity of headache had changed within the first 2 years after withdrawal, but remained stable afterwards. Fifteen patients (39.5%) reported on recurrent drug abuse. Patients with migraine showed a tendency towards a better prognosis compared to patients with tension-type headache or with combined migraine and tension-type headache. The results of this study highlight the long-term efficacy of inpatient drug withdrawal in patients with headache and ergotamine and/or analgesics abuse.

Cyclandelate in the prophylaxis of migraine: a randomized, parallel, double-blind study in comparison with placebo and propranolol

Cyclandelate inhibits calcium-induced contraction of vascular smooth muscle cells, platelet aggregation induced by thrombin, platelet-activating-factor and adenosine, and also suppresses a provoked 5HT release from platelets. This pharmacological profile suggests that cyclandelate may have a potential prophylactic effect in migraine. To test this hypothesis, a double-blind multicentre study was performed in 214 patients to investigate the efficacy and tolerability of cyclandelate compared to placebo and propranolol. After a 4-week baseline period, eligible patients (randomization 3:2:3) were treated for 12 weeks with daily doses of 1.200 mg cyclandelate (n=81), placebo (n=55) or 120 mg propranolol (n=78). The number of migraine attacks (350% responders) and the migraine duration/month were compared based on the difference between baseline and the last 4 weeks of prophylactic treatment. The percentage of patients with a reduction in migraine attacks of 350% treated with cyclancelate (37.0%) or propranolol (42.3%) was not significantly superior to placebo (30.9%; P>0.025). The mean duration of migraine in hours (h) per month decreased in both active treatment groups (cyclandelate: 36.8h, p=0.046; propranolol: 34.4 h, p=0.039) compared to placebo (13.7 h) without reaching statistical significance (alpha/2=0.025). The clinical efficacy of cyclandelate and propranolol was comparable. Adverse experiences were reported by 13 patients (16.0%) treated with cyclandelate, by 5 patients (9.1%) treated with placebo and by 19 patients (24.4%) treated with propranolol. These were drug-related in 7.1% (n=6) of patients treated with cyclandelate and in 9% (n=7) of patients treated with propranolol. In summary, cyclandelate has a comparable efficacy to that of propranolol an established drug of first choice in the prophylaxis of migraine. Both drugs were better than placebo, but not significantly so. Both active treatments were well tolerated. ÿ box

Self-medication of migraine and tension-type headache: summary of the evidence-based recommendations of the Deutsche Migräne und Kopfschmerzgesellschaft (DMKG), the Deutsche Gesellschaft für Neurologie (DGN), the Österreichische Kopfschmerzgesellschaft (ÖKSG) and the Schweizerische Kopfwehgesellschaft (SKG)

The current evidence-based guideline on self-medication in migraine and tension-type headache of the German, Austrian and Swiss headache societies and the German Society of Neurology is addressed to physicians engaged in primary care as well as pharmacists and patients. The guideline is especially concerned with the description of the methodology used, the selection process of the literature used and which evidence the recommendations are based upon. The following recommendations about self-medication in migraine attacks can be made: The efficacy of the fixed-dose combination of acetaminophen, acetylsalicylic acid and caffeine and the monotherapies with ibuprofen or naratriptan or acetaminophen or phenazone are scientifically proven and recommended as first-line therapy. None of the substances used in self-medication in migraine prophylaxis can be seen as effective. Concerning the self-medication in tension-type headache, the following therapies can be recommended as first-line therapy: the fixed-dose combination of acetaminophen, acetylsalicylic acid and caffeine as well as the fixed combination of acetaminophen and caffeine as well as the monotherapies with ibuprofen or acetylsalicylic acid or diclofenac. The four scientific societies hope that this guideline will help to improve the treatment of headaches which largely is initiated by the patients themselves without any consultation with their physicians.

Long‐term results of migraine prophylaxis with flunarizine and beta‐blockers

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

Facial Pain and the Second Edition of the International Classification of Headache Disorders

Background.—Recurrent or chronic facial pain may be a diagnostic challenge. Applying the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD‐II) leaves a considerable number of patients unclassifiable.

use and abuse of analgesics in tension-type headache

Eighty patients suffering from tension-type headache for an average of 21 years were asked to report on all drugs they had ever taken (type, dosage, duration of intake, efficacy) or were taking currently. The patients had consumed on average 6.3 different drugs. The cumulative doses of derivatives of para-aminophenol, pyrazolone, and salicylic acid in some cases reached a maximum of several kilograms. Most drugs were classified by the patients as “moderately effective”. The rating “very effective” was assigned primarily to barbiturates; however, barbiturates are no longer used as components of compound analgesic drugs in Austria. At the time of investigation, patients consumed 2.5 (mean) different drugs, primarily as compound preparations. Seventeen patients (21%) showed signs of possible analgesics- or ergotamine-induced headache and were therefore advised to undergo withdrawal therapy. Our results show that patients with tension-type headache are at considerable risk of becoming drug-dependent and of acquiring analgesics-induced headache.

Tension-type headache in different age groups at two headache centers

&NA; At two headache centers, one for children and adolescents and the other for adults, we investigated patients aged 5–80 years with episodic or chronic tension‐type headache to evaluate the relation between age and headache characteristics as well as analgesics intake. We found an increasing headache frequency and duration, an increasing variability of the headache location, and an increasing frequency of nausea with increasing age. All other headache features did not depend on age. Additionally, our study revealed a marked increase of analgesics use in adults compared to children and adolescents. In conclusion, children, adolescents, and adults referred for tension‐type headache show minor differences in some headache features, but a marked change of analgesics intake. The different headache symptoms may be causally related to age, but an influence of medication or other factors must also be considered.