100 Migraine Drugs, A to Z: hydroxyzine

May 27, 2019

Hydroxyzine (Vistaril) is an underutilized old anti-histamine drug with some unique properties. Just like diphenhydramine (Benadryl) and other older anti-histamine drugs, hydroxyzine causes some sedation. However, it is the only anti-histamine that is officially approved for “anxiety and tension”. It is also approved for itching due to allergic conditions. Off-label (i.e. without FDA-approval) it is used to treat motion sickness, nausea, vomiting, and dizziness.

Hydroxyzine is often used as and adjuvant analgesic, that is as an add-on drug that makes pain medications work better.

A study comparing injections of hydroxyzine, 50 mg with a pain medication nalbuphine 10 mg, with a combination of hydroxyzine and nalbuphine, and with placebo found no benefit from adding hydroxyzine when treating migraines.

A study comparing an injection of hydroxyzine 50 mg plus meperidine (Demerol, a narcotic pain killer), 100 mg was similar to an injection of ketorolac (Toradol) 60 mg in its relief of an acute migraine. Nausea and drowsiness were similar in two groups.

Another study compared hydroxyzine 75 mg intravenously plus meperidine 75 mg intramuscularly to DHE 1 mg IV plus metoclopramide (Reglan) 10 mg IV. Pain reduction was greater with DHE/metoclopramide.

There have been no studies examining the efficacy of hydroxyzine alone, whether as an intravenous or intramuscular injection or as a tablet. It is likely that it will remain an adjuvant or add-on medication for the treatment of migraine headaches.

I sometimes prescribe it to be taken daily to patients whose allergies worsen their migraine headaches or even when there is only a suspicion of an allergic component. It is also useful when anxiety is a contributing factor, which is not unusual since those suffering from migraines are 2-3 times more likely to also have anxiety. For many patients it is too sedating to be taken during the day, unless they are treating an acute attack. Most people take 25 or 50 mg nightly, although some tolerate and benefit from 25 mg taken three times a day.

Written by
Alexander Mauskop, MD
Continue reading
June 7, 2026
News
A new edition of my migraine book and an upcoming conversation with Dr. Sanjay Gupta
An overview of why I updated The End of Migraines: 150 Ways to Stop Your Pain for a 3rd edition, what has changed in migraine treatment, and how a more structured, realistic approach can help people who feel they’ve “tried everything.”
Read article
June 4, 2026
Research
A New Study of Meat Intake, Genetics, and Brain Health
A newly published Swedish study suggests that the relationship between diet and brain aging may be more genetically specific than previously understood. Researchers followed over 2,000 older adults for up to 15 years and found that higher meat consumption was associated with slower cognitive decline and lower dementia risk, but only in those carrying the APOE E4 genetic variant, the most common hereditary risk factor for Alzheimer's disease. This may be relevant for people with headaches.
Read article
June 3, 2026
News
Keynote address at the 22nd Annual Neuroscience Zappulla Research Day
I was honored to be delivering the keynote address at the 22nd Annual Neuroscience Zappulla Research Day on Wednesday, June 3, at the Hackensack Meridian Neuroscience Institute, JFK University Medical Center in Edison, NJ.
Read article
Insights from Dr. Alexander Mauskop on headaches and migraines
Subscribe to the Blog.
Subscribe
Subscribe