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IV Prochlorperazine + Diphenhydramine vs Hydromorphone for Migraines

November 21, 2017

Written by Alex Chen

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The primary outcome (quick and sustained headache relief) was achieved in 60% of the IV prochlorperazine + diphenhydramine group vs 31% in the IV hydromorphone group with a NNT of 4. As a result, the study was stopped early.

Why does this matter?
Migraine patients account for approximately 1.2 million ED visits a year in the USA. Despite the American Headache Society recommending against IV opioids, narcotics are used for analgesia in >50% of migraine patients in the ED. However, RCT data comparing the efficacy of opioids vs common migraine meds such as prochlorperazine are scant. This leads to every physician having his or her own “migraine cocktail.” This study puts the guidelines to the test with a good ole’ fashioned head-to-head comparison.

“60% of the time, it works every time.” – Brian Fantana regarding his migraine cocktail
This was a randomized, double-blinded study with 127 patients that was conducted in 2 EDs in New York City. They included patients ≥21y with moderate to severe migraines. Patients were excluded if they had history of opiate addiction or opiate use in the past month. They either received 10mg IV prochlorperazine + 25mg IV diphenhydramine or 1mg IV hydromorphone with a normal saline vial. The primary outcome was a headache level of mild or none within 2 hours of medication and maintenance of that level for 48 hours without rescue medication.

Patients in the hydromorphone group were more likely to have functional impairment at 1h, more likely to request a second dose, and more likely to require off-protocol analgesia. Also, patients receiving IV hydromorphone had a longer median length of stay by 82 minutes.

It is important to note that this study was stopped early. This poses the risk of overestimating the treatment effect, especially in a smaller trial such as this one. Also, the secondary outcomes regarding number of headache days and functional status could have been affected by recall bias and smaller sample size. However, while you should take the magnitude of the results with a grain of salt, it does add strong evidence to the superiority of non-opioid medications in acute migraine analgesia.

Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology. 2017 Nov 14;89(20):2075-2082. doi: 10.1212/WNL.0000000000004642. Epub 2017 Oct 18.

Reviewed by Clay Smith, MD and Thomas Davis, MD

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