Questions About Combining Hydroxyzine And Buspirone
In our latest question and answer, the pharmacist discusses the combined use of buspirone and hydroxyzine.

Question
Does hydroxyzine have serotonergic effects? Can it safely be taken with buspirone?

Answered by Dr. Brian Staiger, PharmD
Medical Content Reviewed By HelloPharmacist
Staff
Last updated Apr 19, 2025
Answer
This is a great question! It's always a good idea to be cognizant of potential drug interactions, especially for anyone taking medications to manage anxiety or related conditions based on the number of interactions these drugs can have with one another.
Hydroxyzine: An Antihistamine With Broad Effects
Hydroxyzine is classified as a first-generation antihistamine, and like others in this class, it works by competing with histamine at H1-receptor sites throughout the body.
However, unlike common OTC antihistamines for allergies, like Claritin or Zyrtec, hydroxyzine tends to have much broader central nervous system effects. In addition to its antihistamine action, hydroxyzine also has:
- Muscle relaxant properties
- Bronchodilator effects
- Antiemetic activity (helps reduce nausea)
- Mild analgesic properties
- Activity at muscarinic, serotonergic (5HT2), and dopaminergic receptors in the brain, particularly in areas like the hippocampus and cerebral cortex
This broader activity is believed to contribute to hydroxyzine’s anti-anxiety effects. In fact, the drug is FDA approved for the short-term treatment of anxiety, unlike most other antihistamines.
Serotonergic Activity
You asked specifically about the serotonergic activity of hydroxyzine.
Although hydroxyzine does have some interaction with serotonin receptors, particularly weak antagonism at 5HT2 receptors in the hippocampus, this effect is considered minor and not the drug’s main mechanism of action. It’s not typically classified as a serotonergic drug in the way that SSRIs or even buspirone are. It also is not generally associated with serotonergic side effects or the rare, but serious condition of serotonin syndrome.
Buspirone and Hydroxyzine Together
Buspirone is a non-sedating anxiolytic that acts mainly as a partial agonist at serotonin 5HT1A receptors. It works in a completely different way from hydroxyzine, and it does not have strong sedative effects like benzodiazepines or first-gen antihistamines.
Generally, taking buspirone and hydroxyzine together is not considered dangerous. However, hydroxyzine is considered a CNS depressant due to its sedating properties. Buspirone can cause sedation as well (although it tends to be mild). When taken together, there’s a potential for additive sedation, meaning you might feel more tired, groggy, or slowed down than you would on either medication alone.
Is It Safe?
Again, generally, hydroxyzine and buspirone are safe to use together when prescribed by a healthcare provider. Some online drug interaction checkers will list an interaction based on that additive sedation I mentioned.
The main thing to watch for is increased drowsiness or feeling overly sedated. If you notice that, it’s worth checking in with your provider to see if dose adjustments or timing changes could help.
If you're new to either medication or starting them at the same time, avoid activities that require full mental alertness (like driving or operating machinery) until you know how they affect you.
Final Words
Thanks again for reaching out. Please feel free to contact us again if anything comes up!
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Dr. Brian Staiger, PharmD
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