From the Guidelines
Intravenous (IV) Benadryl (diphenhydramine) is not a recommended first-line treatment for migraines, and its use should be considered on a case-by-case basis, particularly in emergency department settings where other treatments have failed or are contraindicated. The typical dose is 25-50 mg administered intravenously, often in combination with other medications such as IV metoclopramide, prochlorperazine, or pain medications. According to the most recent guidelines 1, the recommended first-line treatments for acute migraine attacks include eletriptan, frovatriptan, rizatriptan, sumatriptan, and zolmitriptan, as well as aspirin-acetaminophen-caffeine.
Some key points to consider when using IV Benadryl for migraines include:
- Its ability to counteract side effects of other migraine medications, such as akathisia from antiemetics
- Its provision of mild sedation to help patients rest during an attack
- Its potential direct analgesic properties
- Its antihistamine properties, which may help reduce inflammation associated with migraine pathophysiology
- Common side effects, including drowsiness, dry mouth, and occasionally paradoxical excitation
It's essential to note that IV Benadryl is not FDA-approved specifically for migraine treatment, and its use is considered off-label. However, in emergency settings where first-line treatments are ineffective or contraindicated, IV Benadryl may be considered as an adjunctive treatment, as suggested by older studies 1. Nevertheless, the most recent and highest-quality evidence 1 should guide treatment decisions, prioritizing recommended first-line therapies and reserving IV Benadryl for specific cases where its benefits outweigh the risks.
From the Research
Role of IV Benadryl in Migraine Treatment
- IV Benadryl (diphenhydramine) is not typically considered a first-line treatment for migraines, but it may be used as an adjunct therapy 2.
- In one study, IV diphenhydramine was administered in combination with prochlorperazine or metoclopramide for the treatment of acute migraine, and both combinations were found to be efficacious 2.
- However, there is limited evidence to support the use of IV Benadryl as a standalone treatment for migraines, and its effectiveness and safety in this context are not well established 3, 4, 5.
- Other medications, such as metoclopramide, prochlorperazine, and sumatriptan, have more robust evidence supporting their use as first-line treatments for migraines 4, 6.
- The American Headache Society recommends using injectable non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen as second-line treatments for migraines, but does not mention IV Benadryl as a recommended treatment 3.
Key Findings
- A study published in 2008 found that IV prochlorperazine and metoclopramide, both combined with IV diphenhydramine, were effective treatments for acute migraine 2.
- A 2016 guideline from the American Headache Society recommends using metoclopramide, prochlorperazine, and sumatriptan as first-line treatments for migraines, but does not mention IV Benadryl 4.
- A 2024 systematic review and Bayesian network meta-analysis found that chlorpromazine IV/IM was the most likely to be superior for adequate pain relief at 2 hours, but did not evaluate IV Benadryl as a treatment option 5.