Magnesium Versus Prochlorperazine Versus Metoclopramide for Migraines

Migraine or severe headache affected one-fifth of women and one-tenth of men in 2015 and is one of the leading causes of disability in the world. Over one million visits to emergency departments (ED) in the US are due to migraines. Migraine, previously believed to be a vascular disorder, is caused by inflammation due to vasodilation in the meninges secondary to the release of vasoactive neuropeptides by stimulation of the trigeminal nerve. This inflammation can result in symptoms such as headache, nausea, vomiting, dizziness, photophobia and phonophobia.

Despite migraine being a common disorder, there has yet to be a cure. Several classes of medications have been studied for the treatment of migraine. Recently, conventional therapy has shifted to the use of antidopaminergics including prochlorperazine, metoclopramide and haloperidol, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and triptans, sumatriptan being the most commonly utilized. 5Although intravenous opioids have historically been the most common treatment for migraines, their use has fallen out of favor due to their association with increased recurrence of headaches and ED visits, abuse potential, and most recently severe intravenous opiate shortage. Alternative treatments include ketamine, propofol, dihydroergotamine and magnesium.

Magnesium is an intracellular cation that has been associated with both the function of serotonin and regulation of vascular tone, which are both mechanisms that implicate its role in the treatment of migraine. Intravenous magnesium sulfate has been studied as a treatment for migraine compared to placebo, metoclopramide and prochlorperazine. These studies have shown that magnesium is well-tolerated with a good safety profile and may be efficacious in the treatment of migraine. Metoclopramide, prochlorperazine and magnesium have been recommended in clinical practice guidelines and have become routine standard of care for treatment of migraine in this emergency department. However, no trial has evaluated these modalities simultaneously in the same population. The purpose of our study is to compare the relative efficacy for magnesium, metoclopramide, and prochlorperazine in the treatment of headache and migraine.

Via monthly block randomization, patients will be given one of three guideline recommended study drugs. Allocation will be concealed by a pharmacist (not participating in the rest of the study) solely designated to choose which drug will be the assigned study drug for each month. The pharmacists, physicians, and nurses participating in administration of the medications will be blinded to which drug is being administered during each month. Metoclopramide, prochlorperazine and magnesium have been recommended in clinical practice guidelines and have become routine standard of care for treatment of migraine in this emergency department. All three study drugs will be stored in the investigational medication refrigerator located in the main pharmacy. A pharmacist on duty in the emergency department will obtain the medication from the refrigerator and deliver it to the bedside nurse who is actively caring for the patient after an order from the physician.

The primary outcome of this study will be mean change in pain from baseline to 30 minutes after initiation of infusion (as defined on a 11-point Numeric Rating Scale. Secondary endpoints include mean change in pain from baseline to 60 minutes and 120 minutes after initiation of infusion (as defined on a 11-point Numeric Rating Scale), time to emergency department discharge, and adverse effects due to administration of study drug (hypotension, flushing, akathisia, dystonia, nausea, vomiting, dizziness, drowsiness, other self-reported adverse effects).

• Magnesium Sulfate (Drug): Magnesium Sulfate 2gm in 50ml D5W over 20 minutes
• Metoclopramide 10mg (Drug): Metoclopramide 10mg in 50ml D5W over 20 minutes
• Prochlorperazine (Compazine) Injection (Drug): Prochlorperazine 10mg in 50ml D5W over 20 minutes

Primary outcomes

• 30 Minute Pain Score [30 minutes after initiation]: Scores range from 0-10. A higher score, denotes more pain

Secondary outcomes

• Length of Stay [From time of arrival to time of discharge.]: Emergency Department Length of stay. Measured from time of arrival to time of discharged documented in the electronic medical record.
• Need for Rescue Analgesia [From time of arrival to time of discharge.]: Percentage of participants who had necessity for rescue analgesics after study drug administration

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Age > 18 years or older
* Able to provide informed consent
* Primary diagnosis of headache or migraine
* Between October 1, 2018 to April 1, 2020
* Presenting to Advocate Christ Medical Center emergency department and meet clinical assessment per physician

Exclusion Criteria:

* Pregnancy defined as a positive urine HCG
* Stated history of renal impairment
* Allergy or sensitivity to any study drugs
* Concomitant treatment at the time of study drug administered in the emergency department
* Patients with a history of this study participation

Participant flow

Outcome results

• 30 Minute Pain Score (Primary), Median, score on a scale: Magnesium 3 (1 to 4); Metoclopramide 3 (1 to 4); Prochlorperazine 3 (1 to 5)
• Length of Stay (Secondary), Median, minutes: Magnesium 325 (274 to 410); Metoclopramide 308 (263.5 to 403); Prochlorperazine 332 (268.5 to 391)
• Need for Rescue Analgesia (Secondary), Count of participants, Participants: Magnesium 26; Metoclopramide 15; Prochlorperazine 17

Adverse events

Time frame: Adverse effects were investigated at every VAS evaluation time time point, 30 minutes, 60 minutes, and 120 minutes.

• Study Protocol and Statistical Analysis Plan (PDF, 2020-09-10)

• Michael Cirone, MD, Principal investigator, advocate christ medical center