What is the recommended administration time for magnesium sulfate when used as a headache abortive? Is there literature supporting administration 2 gm over 20 minutes?

Comment by InpharmD Researcher

There is no clear consensus on the optimal dose or infusion rate of intravenous (IV) magnesium sulfate for aborting acute migraine or non-traumatic headache, and available data are heterogeneous. Most studies report 1-2 g infused over 10-20 minutes, with pain relief assessed 30-120 minutes after infusion. Some trials show benefit, particularly after 1 hour, while others find no significant improvement versus controls. One prospective trial evaluated 2 g over 20 minutes compared with metoclopramide or prochlorperazine, suggesting magnesium can be a feasible alternative or adjunct (see Kandil et al., in Table 1). Additionally, an ongoing study is assessing 2 g over 20 minutes combined with paracetamol (acetaminophen), though results are not yet available. Based on overall findings, IV magnesium appears potentially beneficial, but the evidence regarding optimal administration remains limited.

Background

A meta-analysis published in 2014 included 5 of the randomized controlled trials (RCTs; N= 295; Frank et al., Cete et al., Ginder et al., Corbo et al., Bigal et al., Demirkaya et al.) to assess the efficacy and tolerability of intravenous (IV) magnesium sulfate for the treatment of acute migraine in adults. The magnesium infusion was given either 1 or 2 g over 10 to 20 minutes. The results showed that the proportion of patients with pain relief from a headache at 30 min post-treatment was 7% lower in the magnesium group compared with the controls (pooled risk difference -0.07; 95% confidence interval [CI] -0.23 to 0.09). However, the adverse events occurred more frequently in the magnesium group by 37% compared with the controls (pooled risk difference 0.370; 95% CI 0.06 to 0.68). The percentage of patients who needed rescue analgesic medications was slightly lower in the control groups, but without any statistical significance (pooled risk difference -0.021; 95% CI -0.16 to 0.12). Based on these main findings, the authors concluded that IV magnesium did not show clinical benefits in terms of reduction in pain relief in acute migraine and in terms of the need for rescue medication. Yet, a higher incidence of adverse events was reported in the magnesium group compared to the controls. The authors noted that most included studies were underpowered, the study populations were based on convenience sampling, and some did not report inclusion and exclusion criteria in sufficient detail. [1]

Another meta-analysis published in 2016 examining the effects of IV and oral magnesium in reducing acute migraines included 21 studies of which 11 studies investigated the effects of IV magnesium (N= 948). Conflicting with a meta-analysis discussed above, the results showed that the IV magnesium significantly reduced acute migraine within 15-45 minutes, 120 minutes, and 24 hours after the initial infusion (odd ratios [OR] 0.23, 0.20, and 0.25, respectively). Of the included IV magnesium studies, two administered magnesium sulfate 2 g over 10-15 mins (Cete et al, Corbo et al) and three administered 1 g over 15-20 mins (Bigal et al, Demirkaya et al, Shahrami et al). The authors concluded that IV magnesium has beneficial effects in relieving acute migraine attacks; however, given the lack of adequate randomization methods among included trials and potential for selection bias, the authors also stated that the findings should be interpreted with caution. [2]

An additional systematic review including 7 RCTs (N= 545; Bigal et al, Cete et al, Corbo et el, Frank et al, Ginder et al, Rahimdel et al, Shahrami et al) that used either 1 or 2 g of IV magnesium sulfate given over 10-20 minutes to treat either migraine headaches or benign non-traumatic headaches in the ED revealed that the pain intensity was improved with magnesium sulfate vs. comparators at 60-120 minutes, but not at earlier time points. Given the significant methodological heterogeneity between the studies, the authors were unable to provide conclusions on the efficacy of IV magnesium in treating acute headaches. However, the authors suggested that there might be potential benefits in pain control beyond 1 hour, aura duration, and the need for rescue analgesia. [3]

An ongoing phase 3, randomized, parallel-group trial with an estimated enrollment of 424 patients, currently recruiting, is evaluating IV magnesium sulfate for non-traumatic acute headache in the emergency department. According to the study protocol provided in the Clinical Trials Database, 2 g IV magnesium sulfate will be administered over 20 minutes in combination with 1 g of paracetamol (acetaminophen), compared with placebo infusion. The trial is anticipated to be completed in December 2026; given that the trial is still in the recruitment phase, findings are not yet available. [4]

References: [1] Choi H, Parmar N. The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials. Eur J Emerg Med. 2014;21(1):2-9. doi:10.1097/MEJ.0b013e3283646e1b.
[2] Chiu HY, Yeh TH, Huang YC, et al. Effects of intravenous and oral magnesium on reducing migraine: a meta-analysis of randomized controlled trials. Pain Physician. 2016;19(1):E97-112.
[3] Miller AC, K Pfeffer B, Lawson MR, et al. Intravenous magnesium sulfate to treat acute headaches in the emergency department: a systematic review. Headache. 2019;59(10):1674-1686. doi:10.1111/head.13648.
[4] ClinicalTrials.gov. Intravenous Magnesium Sulfate Vs Placebo to Treat Non -Traumatic Acute Headaches in the Emergency Department. Updated February 28, 2024. Accessed March 26, 2026. https://clinicaltrials.gov/study/NCT05325580
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the recommended administration time for magnesium sulfate when used as a headache abortive? Is there literature supporting administration 2 gm over 20 minutes?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Table 1 for your response.

Intravenous Magnesium Sulfate for Treating Migranes

  

Authors and Published Year

Study Design and Objective

Study Groups and Interventions 

 Efficacy Outcomes Safety Outcomes Conclusions

Mauskop et al. (1995)

Case series

To examine the possibility that patients with cluster headaches and low ionized magnesium levels may respond to an intravenous (IV) infusion of magnesium sulfate (MgSO4)

N=22 (38 infusions)

An IV infusion of 1 g MgSO4 was given in a 10% solution over a period of 5 minutes with patients in a recumbent position.

76% of the infusions showed a correlation between a pain relief response and an ionized magnesium level below 0.54 mmol/L; only 9 out of the 22 (41%) patients reported clinically meaningful improvements

 None discussed.

Spontaneous remissions and a placebo effect might have accounted for some of the improvements.

Measurements of ionized magnesium may prove useful in elucidating the pathogenesis of cluster headache and in identifying patients who may benefit from treatment with magnesium.

Ginder et al. (2000)

Randomized double-blind study

To determine whether IV MgSO4 is effective in headache relief when compared with IV prochlorperazine in an emergency department (ED) setting and if responders to MgSO4 have low serum IMg levels

 

N=36; MgSO4 (n=16), Prochloreperazine (n=20)

Eligible patients were randomized to receive 50-mL bags of either 2 g of MgSO4 or 10 mg of prochlorperazine and infused over 10 minutes.

Complete pain relief was achieved in 40% (±21%) of the prochlorperazine group as opposed to 12% (±16%) in the MgSO4 group (P=0.016).

Dysphoria occurred in 1 patient (5%) in the prochlorperazine group.

A total of 5 adverse events (31%) occurred in the magnesium group: 4 instances of IV burning or pain and 1 of emesis.

The most frequent (60%) adverse effect in the MgSO4 group, burning at the IV site, might be alleviated by a slower infusion rate.

It was determined that IV prochlorperazine is highly effective in the treatment of headaches and magnesium is moderately effective. Response to MgSO4 was unrelated to serum Mg level.

Demirkaya et al. (2001)

Randomized single-blind placebo-controlled trial

To study the efficacy and tolerability of 1 g of IV MgSO4 as acute treatment of moderate or severe migraine attacks

N=30; IV MgSO4 (n=15), Placebo (n=15)

Fifteen patients received 1 g IV MgSO4 over 15 minutes. The next 15 patients received 10 mL of 0.9% saline IV. Those in the placebo group with persisting complaints of pain or nausea and vomiting after 30 minutes also received 1 g IV MgSO4 over 15 minutes.

All patients in the treatment group responded to magnesium sulfate. The pain disappeared in 13 patients (86.6%) and diminished in 2 patients (13.4%). IV MgSO4 group all had accompanying symptoms disappeared.

Fourteen of the 15 placebo-received patients reported no change in pain intensity, and only 3 patients reported resolution in the accompanying symptoms. All were subsequently given MgSO4, and all responded to magnesium sulfate.

 None discussed. 1 g IV MgSO4 is an efficient, safe, and well-tolerated drug in the treatment of migraine attacks.

Corbo et al. (2001) 

Randomized double-blind placebo-controlled trial

To test whether IV MgSO4 is an effective adjunctive medication for the treatment of acute migraine in an ED setting

N=44; Magnesium + metoclopramide (n=21), Placebo + metoclopramide (n=23)

All participants received IV metoclopramide 20 mg over 2 mins before receiving either IV MgSO4 2 g or placebo (saline) over 10 minutes. Doses were repeated every 15 mins as needed for pain for up to three total doses.

Both groups experienced a more than 50-mm improvement in visual analog scale (VAS) score. However, the improvement was smaller in the magnesium group (16-mm difference favoring placebo [95% CI –2 to 34 mm]), as was the proportion with normal functional status at the final rating (36% absolute difference favoring placebo [95% CI 7% to 65%])

 Of the 14 patients in the metoclopramide plus magnesium group (vs. 6 patients in the placebo group) reported adverse effects, 10 experienced flushing, 2 reported dizziness, 1 experienced total body burning, and 1 reported drowsiness. Intravenous magnesium sulfate does not appear to be an effective adjunct in the treatment of acute migraine in women (95% of the study population) when used in combination with metoclopramide.

Zidverc-Trajković et al.(2001)

Open-label, comparative study

To estimate the efficacy of intravenous magnesium sulfate in the treatment of severe migraine attacks

N=36; Magnesium sulfate (n=22), Sumatriptan (n=14)

Patients were treated with magnesium sulfate 1 g infusion over 3-5 minutes. The results were compared to another group of patients who were treated with sumatriptan 6 mg subcutaneously.

Efficacy of sumatriptan was superior that of to magnesium sulfate 20 minutes after the injections (p<0.05) and comparable after 30 minutes (magnesium therapy was successful in 68% in comparison to 79% of patients treated with sumatriptan).

Three patients treated with magnesium sulfate were pain-free after 10 minutes. Five (22.5%) and 10 (45%) patients were pain-free after 20 and 30 minutes, respectively.

 No other adverse events were noted except for a moderate sensation of warmth at the site of injection in all patients and a case of palpitations in one patient treated with magnesium sulfate. Intravenous magnesium sulfate may be a well-tolerated pharmacological alternative for the treatment of severe migraine attacks.

Bigal et al. (2002)

Randomized, double-blind, placebo-controlled trial

To assess the effect of magnesium sulfate on the pain and associated symptoms in patients with migraine without aura (MO) and migraine with aura (MA)

N=60; MO (n=30), MA (n=30)

Eligible patients were randomized to receive either an IV injection of 1 g MgSO4 or 10 ml 0.9% normal saline infused over 20 minutes.

In the migraines without aura group, no statistically significant difference was observed in pain or nausea relief between the magnesium and placebo, but a significantly lower intensity of photophobia and phonophobia was observed in patients who received magnesium sulfate. 

In the migraine with aura group, statistically significant improvements in pain and all associated symptoms were observed with magnesium therapy as compared to placebo.

 None discussed.  Our data support the idea that magnesium sulfate can be used for the treatment of all symptoms in migraine with aura, or as adjuvant therapy for associated symptoms in patients with migraine without aura.

Frank et al. (2004)

Randomized double-blind placebo-controlled trial

To investigate the effectiveness of IV magnesium sulfate in patients with acute benign headaches who presented to the ED

N=42; Magnesum (n=21), Placebo (n=21)

Eligible patients were randomized to receive either a 2 g of IV magnesium sulfate or placebo (normal saline) infused over 10 minutes.  Pre- and post-treatment pain scores were measured on a 100-mm visual analog pain scale.

Following the treatment, the placebo group reported an 8-mm median improvement in pain, whereas, magnesium recipients had a 3-mm improvement (p=0.63). No statistically significant differences between the groups for any secondary outcomes were found, as well.

Thirteen patients (62%) in the magnesium group reported adverse effects, whereas only 6 patients in the placebo group (p=0.03).

In the placebo group, 2 had a decrease in blood pressure, 1 had hot flashes, 1 had burning at the IV site and 2 had other symptoms.

In the magnesium group, 1 had a decrease in blood pressure, 2 had burning at the IV site, 9 had flushing and 1 had other symptoms.

 The study found no benefit to using IV magnesium to treat patients with acute benign headaches who present to the ED.

Cete et al. (2005)

Randomized double-blind placebo-controlled trial

To determine the effectiveness of IV magnesium sulfate and IV metoclopramide in the treatment of acute migraine attacks in the ED when compared with placebo

N=113; Metoclopramide (n=37), Magnesium (n=3), Placebo (n=40)

Eligible patients were randomized to receive either 10 mg of IV metoclopramide, 2 g of IV magnesium sulfate, or normal saline over 10 minutes. At 0, 15, and 30 min, patients were asked to rate their pain on a standard VAS.

No statistically significant difference was detected in the mean changes in VAS scores for pain between the magnesium, metoclopramide, and placebo group. Patients receiving a placebo required a higher rate of rescue medication.

Side effects were seen in four (4%) of the 113 patients.

In the metoclopramide group, one (3%) patient developed a dystonic reaction shortly after infusion, and flushing was seen in three (8%) patients who received magnesium. 

Although patients receiving placebo required rescue medication more than the others, metoclopramide and magnesium have an analgesic effect similar to placebo in migraine attacks.

IV magnesium sulfate and metoclopramide are no more effective than placebo in the treatment of acute migraine attacks. 

Rahimdel et al. (2007)

Randomized double-blinded controlled trial

To compare the effects of magnesium sulfate and dihydroergotamine (DHE) in the management of severe migraine headaches in the ED

N=120; Magnesium sulfate (n=60), Dihydroergotamine (n=60)

Eligible patients were randomized to receive either 1g IV magnesium sulfate or DHE (standard treatment of acute migraine). The duration of infusions was not specified. 

The mean VAS was 6 ± 1.29,  4.08 ± 1.67, and, 2.48 ± 1.61  in the magnesium group and 5.85 ± 1.02, 4.62 ± 1.21, and 3.48 ± 1.26 in the DHE group after 30, 60, and 90 mins of infusion, respectively. Pain score comparisons were statistically significant at 60 and 90 minutes. 

 None specifically discussed.

Treatment with 1g of magnesium sulfate in 100 ml normal saline solution provides significant pain relief in migraine without any serious side effects.

Shahrami et al.(2015)

Randomized double-blind controlled trial

To evaluate and compare the effects of magnesium sulfate and combined use of dexamethasone/metoclopramide on relieving acute migraine headache in the ED

N=70; dexamethasone/metoclopramide (n=35), magnesium sulfate (n=35)

Eligible patients were randomized to receive either 8 mg dexamethasone/10 mg metoclopramide or 1 g magnesium sulfate infused over 15 minutes. Pain severity was evaluated at 20 min and at 1- and 2-h intervals post-infusion. 

Magnesium sulfate was associated with decreased pain severity at all three intervals (5.2 ± 1.7, 2.3 ± 1.9, and 1.3 ± 0.66, respectively), exhibiting significant differences compared to baseline values and the corresponding time intervals in the dexamethasone/metoclopramide group (p<0.0001).

In the dexamethasone/metoclopramide group, statistically significant differences were found only between the baseline values and 1-h and 2-h interval values. 

Even though no significant adverse events were observed between the groups (p=0.78); more patients in the magnesium group reported "no complications" compared to the dexamethasone/metoclopramide group (88.6% vs. 80.0%).

In the magnesium group, only 4 complications were reported which were all nausea. 

Magnesium sulfate was a more effective and fast-acting medication compared to a combination of dexamethasone/metoclopramide for the treatment of acute migraine headaches.

Dexamethasone may decrease the efficacy of metoclopramide when used in combination to treat migraine headaches

Baratloo et al. (2017)

Prospective quasi-experimental study

To investigate the efficacy of intravenous caffeine citrate vs. magnesium sulfate for management of acute migraine headache in the ED

N=70; Caffeine (n=35), Magnesium sulfate (n=35)

Patients were allocated to receive either 60 mg intravenous caffeine or 2 g intravenous magnesium sulfate infused over 10 minutes. 

 Both IV caffeine citrate and IV magnesium sulfate significantly reduced pain scores yet the magnesium sulfate group showed more improvement than the caffeine citrate group after one hour (p<0.001) and after two hours (p<0.001). No cases of serious adverse events were noted in both groups. 

It is likely that both intravenous caffeine and intravenous magnesium sulfate can reduce the severity of migraine headaches. Moreover, intravenous magnesium sulfate at a dose of 2 g might be superior to intravenous caffeine citrate 60 mg for the short-term management of migraine headaches in emergency departments.

Xu et al.  (2019)

Retrospective chart review/ exploratory study

To investigate the effectiveness of intravenous magnesium as an abortive for status migrainosus in an outpatient infusion center, and characterize the patients who benefit from the therapy

N=234

Retrospective analysis of migraine patients who received IV magnesium as a headache abortive, at the headache clinic of the University of Southern California was conducted. 

Additional intramuscular (IM) injections for nausea or for refractory pain were administered as necessary. 

Overall, the pain scores decreased from 5.46±2.39 to 3.56 ± 2.75 (p<0.001) after magnesium infusion. 127 patients (54%) had clinically significant pain reduction (defined as pain decrease ≥ 30%). 144 patients (44%) received IV magnesium and did not require additional IM medications for pain. 

 

Only 2 patients reported adverse effects, one with transient hypotension and the other with diarrhea.

For a subset of patients with status migrainosus, IV magnesium therapy results in clinically significant pain relief without the need for intramuscular pain medications. Therefore, IV magnesium may be useful as a cost-effective first-line parental therapy for status migrainosus, especially for patients who initially present with lower pain intensity.

It is the largest observational study concerning the use of IV magnesium in the treatment of status migrainosus.

Kandil et al. (2021)

Prospective randomized double-blind trial

To compare the relative efficacy of magnesium, metoclopramide, and prochlorperazine for the treatment of headache and migraine in the ED

N=157; Magnesium (n=61), Metoclopramide (n=44), Prochlorperazine (n=52)

Patients were randomized to receive either one of three study drugs (Magnesium sulfate 2 g/50 mL D5W, prochlorperazine 10 mg/50 mL D5W, or metoclopramide 10 mg/50 mL D5W) as an IV infusion over 20 min.

Over 70% of patients received a dose of IV diphenhydramine prior to the study medication to prevent potential adverse effects such as akathisias.

IV magnesium was not inferior to prochlorperazine or metoclopramide at 30 min in treating headaches and migraines in the ED based on the reported numeric rating scale (NRS).

The median decrease in NRS (IQR) at 60 min was −4 (2–6) in the magnesium group, −3 (2–5) in the metoclopramide group, and −4.5 (2–7) in the prochlorperazine group (p=0.27). 

No statistically significant differences were observed in ED length of stay, rescue analgesia, or adverse effects.

Adverse events were reported in 5% of patients in the magnesium group, 4.5% in the metoclopramide group, and 11.5% in the prochlorperazine group (p=0.51).

The most reported adverse effects were dizziness, anxiety, and akathisia (specific to prochlorperazine group only).

 IV magnesium may be used as an adjunctive agent for the treatment of migraines or may serve as a safe alternative when agents such as prochlorperazine or metoclopramide are not appropriate. 
References:
[1] [1] Mauskop A, Altura BT, Cracco RQ, et al. Intravenous magnesium sulfate relieves cluster headaches in patients with low serum ionized magnesium levels. Headache. 1995;35(10):597-600. doi:10.1111/j.1526-4610.1995.hed3510597.x.
[2] [2] Ginder S, Oatman B, Pollack M. A prospective study of i.v. magnesium and i.v. prochlorperazine in the treatment of headaches. J Emerg Med. 2000;18(3):311-315. doi:10.1016/s0736-4679(99)00220-6.
[3] [3] Demirkaya S, Vural O, Dora B, et al. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache. 2001;41(2):171-177. doi:10.1046/j.1526-4610.2001.111006171.x.
[4] [4] Corbo J, Esses D, Bijur PE, et al. Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache. Ann Emerg Med. 2001;38(6):621-627.
[5] [5] Zidverc-Trajkovi J, Pavlovi AM, Jovanovi Z, et al. Efficacy of intravenous magnesium sulfate in severe migraine attacks. J Headache Pain. 2001;2(2):79-82.
[6] [6] Bigal ME, Bordini CA, Tepper SJ, et al. Intravenous magnesium sulfate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia. 2002;22(5):345-353. doi:10.1046/j.1468-2982.2002.00364.x.
[7] [7] Frank LR, Olson CM, Shuler KB, et al. Intravenous magnesium for acute benign headache in the emergency department: a randomized double-blind placebo-controlled trial. CJEM. 2004;6(5):327-32. doi:10.1017/s1481803500009593.
[8] [8] Cete Y, Dora B, Ertan C, et al. A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the Emergency Department. Cephalalgia. 2005;25(3):199-204. doi:10.1111/j.1468-2982.2004.00840.x.
[9] [9] Rahimdel A, Eslami MA, Zeinali A. A randomized controlled study of magnesium sulfate versus dihydroergotamine in the management of acute migraine attacks. Pak J Neurol Sci. 2007;2:92-95.
[10] [10] Shahrami A, Assarzadegan F, Hatamabadi HR, et al. Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache. J Emerg Med. 2015;48(1):69-76. doi:10.1016/j.jemermed.2014.06.055.
[11] [11] Baratloo A, Mirbaha S, Delavar Kasmaei H, et al. Intravenous caffeine citrate vs. magnesium sulfate for reducing pain in patients with acute migraine headache; a prospective quasi-experimental study. Korean J Pain. 2017;30(3):176-182. doi:10.3344/kjp.2017.30.3.176.
[12] [12] Xu F, Arakelyan A, Spitzberg A, et al. Experiences of an outpatient infusion center with intravenous magnesium therapy for status migrainosus. Clin Neurol Neurosurg. 2019;178:31-35. doi:10.1016/j.clineuro.2019.01.007.
[13] [13] Kandil M, Jaber S, Desai D, et al. MAGraine: Magnesium compared to conventional therapy for treatment of migraines. Am J Emerg Med. 2021;39:28-33. doi:10.1016/j.ajem.2020.09.033.