Written by Amanda Mathews
Spoon Feed
There was no clear choice for single-agent pain control, but chlorpromazine IV/IM was among the most effective for pain relief at two hours, and IV/IM ketorolac was among the worst.
Figuring out a migraine cocktail is a headache
Researchers identified 64 trials to include in this Bayesian network meta-analysis. The four outcomes were: 1) adequate pain relief at 2 hours, 2) change in pain intensity at 1 hour, 3) need for rescue drug at 2 hours, and 4) significant adverse reaction.
Chlorpromazine (a.k.a. Thorazine) IV/IM (OR 9.79, 95%CrI 3.42 to 24.42), prochlorperazine (a.k.a. Compazine) IV/IM (OR 8.10, 95%CrI 2.91 to 22.44), propofol (OR 5.77, 95%CrI 1.45 to 24.04), and metoclopramide IV/IM (OR 3.91, 95%CrI 1.93 to 8.11) had improved pain relief at 2 hours compared to placebo. Additional probabilistic analysis showed that chlorpromazine is most likely to be superior at 2 hours amongst this group. However, IV/IM ketorolac is possibly the least effective single agent for pain relief.
In comparison with placebo, two drugs were associated with increased likelihood of significant adverse reaction: propofol (OR 11.11, 95%CrI 1.25 to 100.00) and chlorpromazine IV (OR 4.17, 95%CrI 1.64 to 12.50).
There was significant heterogeneity among trials, and most compared individual medications against placebo. Doses and routes of administration (IV/IM) differed across studies, and some drugs (propofol, dexketoprofen, and lidocaine) are rarely used at U.S. hospitals for migraine. Ultimately, conclusions were based on low- or very low-certainty evidence, indicating the need for further randomized controlled trials.
How will this change my practice?
It seems every EM provider has an opinion on the “correct” migraine cocktail, from a single drug to the “Full Neuro,” with eight drugs and a liter of fluid. Unfortunately, this large study does not settle the debate. Medications for migraines have pros and cons, and while chlorpromazine performs best, it has more adverse reactions. I will continue to use my first-line migraine cocktail and keep in mind additional medications for further rounds of treatment if necessary.
Source
Effectiveness and Safety of Pharmacologic Therapies for Migraine in the Emergency Department: A Systematic Review and Bayesian Network Meta-analysis. Ann Emerg Med. 2025 Apr;85(4):313-329. doi: 10.1016/j.annemergmed.2024.11.004. Epub 2024 Dec 14. PMID: 39674934
