Magnesium in the Prophylaxis of Migraine—a Double-Blind, Placebo-Controlled Study

Abstract

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.

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

“…This side effect seems to occur only with oral intake of magnesium, as we did not encounter any gastrointestinal side effects in our study with intravenous MgSO 4 [43], nor did Mauskop et al in a similar study [44]. Our total frequency of side effects with magnesium (47.8%) is comparable to that in other studies which reported frequencies of 37.2% [21] and 45.7% [20]. Our higher rate of side effects might result from the higher doses of magnesium we used.…”

“…Diarrhea was only seen in 1 patient (4%). This number is somewhat higher than in the studies of Pfaffenrath et al [20] (28.6%) and of Peikert et al [21] (18.6%), but in the latter study 2 patients (5%) had to discontinue treatment because of diarrhea [21]. This side effect seems to occur only with oral intake of magnesium, as we did not encounter any gastrointestinal side effects in our study with intravenous MgSO 4 [43], nor did Mauskop et al in a similar study [44].…”

“…This has led to trials questioning the utility of magnesium as a therapeutic choice in the prophylaxis of migraine [19][20][21]22]. In most of these trials oral magnesium therapy has been shown to reduce attack frequency significantly when compared to placebo [19,21,22].…”

“…Peikert et al [21] reported that magnesium was even significantly superior to placebo at the end of the second month, which was also the fact in our study. Pfaffenrath et al [20], on the contrary, found no benefit of magnesium compared to placebo during an interim analysis and decided to discontinue their trial.…”

“…Studies using magnesium for the prophylactic treatment of migraine have gained interest lately [19][20][21][22], most of them showing a good prophylactic effect of magne-sium versus placebo and a good tolerability of the drug [19,21,22]. Although there have been placebo-controlled trials investigating magnesium in migraine prophylaxis, no study has compared magnesium to other drugs commonly used in migraine prophylaxis.…”