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
September 17, 2026
Music and Pain
Music can relieve pain, but what kind of music?
Read article
September 10, 2026
Brain disorders
Genetic connection of fibromyalgia with low back pain, PTSD, IBS, and other disorders.
A genome-wide study published in Nature Medicine found that fibromyalgia shares genetic risk factors with chronic pain conditions, IBS, PTSD, and sleep disturbances. This supports treating these overlapping conditions as one problem of a hyperexcitable nervous system rather than as separate diseases, using a multidisciplinary approach that combines psychological therapies with medications, injections, and neurostimulation.
Read article
August 23, 2026
Alternative Therapies
The Butterfly Effect in Migraine: When Tiny Doses Bring Big Relief
Sometimes a small dose of a drug or a natural substance can produce an outsized positive effect
Read article
Insights from Dr. Alexander Mauskop on headaches and migraines
Subscribe to the Blog.
Subscribe
Subscribe