Hydroxyzine is low risk but also low efficacy: it works, just not all that well. We use it mostly as a non-habit-forming sleep aid, a fair alternative to trazodone and gabapentin, and as a PRN for patients who need one instead of a benzodiazepine, especially with allergies or itching. The main limit is sedation, which is why we mostly dose it at night.
When we reach for it
Low risk but low efficacy: it works, but it does not work all that well. Do not be too afraid to push it to 100 mg for sleep; it seems well tolerated.
“It's low risk, but it's low efficacy, unfortunately. It works, but it doesn't work all that well. Shouldn't be too afraid to push it to 100 milligrams. Seems to be well tolerated in those who are well tolerated”
43:27Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026 We will hand it out because it is low risk, and some people just seem to like it. The main dividing line is how sedated they get.
“I don't love hydroxyzine, but I will hand it out because it's a low-risk medication, generally speaking. Some people just seem to like it. I think the main dividing line is how sedated you get on it. Some people just get way too sedated on hydroxyzine”
28:47Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 Hydroxyzine, trazodone and gabapentin are the broadly applicable sleep medications for most to all disorders, with melatonin as a runner-up.
“The broadly applicable medications for sleep in most to all disorders are therefore hydroxyzine, trazodone, and gabapentin. And melatonin is a runner-up because it's not regulated and it kind of depends on which one you buy”
28:18Insomnia and Sleep Medications in PsychiatryDec 2024 When starting an antidepressant, give a non-habit-forming sleeper from day one. Trazodone and gabapentin come first; hydroxyzine is a fair choice if those do not suit. Most depressed patients have sleep problems that one medication will not fix right away.
“on day one, I will give sleepers. And by that, I mean the non-habit-forming ones that are more likely to support deep, healthy sleep, trazodone, gabapentin, are my first lines for that. If you can't tolerate or have to take something else for some reason, hydroxyzine is a fair choice too”
36:32Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 Also said in 1 more episode
“Why am I on the augment team? Because I find that one medication usually doesn't immediately treat all the ill effects of depression right away. Most people have sleep problems. Obviously, those sleep problems tend to improve when you've gotten someone to an adequate dose of SSRI”
15:31Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 For sleep in PTSD, trazodone or gabapentin usually, and hydroxyzine is just fine too.
“I give some kind of a medication. It's usually trazodone or gabapentin. Hydroxyzine is just fine, too. I avoid anticholinergics like Benadryl, if I can help it”
11:41PTSD Medications: Integrating Pharmacotherapy, Therapy, and the Treatment Frame | Episode 22Apr 2025 Skip the classic benzodiazepine bridge with an SSRI. If a patient truly needs a PRN, use gabapentin or hydroxyzine.
“So yes, I don't do the classical thing of benzos with the first couple weeks of the SRI. I don't do that. If they want a PRN, they need a PRN for some reason, I still encourage against it. I'm not going to not use it if the clinical situation is right for it. I'll use gabapentin or hydroxyzine”
22:05Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 Reach for it when someone has a lot of allergies, itching or sleep problems and is not sensitive to antihistamines. For anxiety, it is just not terribly good.
“if someone's got a lot of allergies, if they're not sensitive to antihistamines, if they've got sleep problems, they have itching, go ahead, reach for the hydroxyzine. But to me, it's just not terribly good”
48:07Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026
Dosing
Pamoate versus hydrochloride: one of us pays zero attention to it, has seen no difference in practice, and found no evidence of one.
“I really pay zero attention to it and have not found a difference in my practice. I just prescribed. I don't even know what I'm clicking on. And in my opinion, from what I reviewed in the past, and I didn't review it very long, there was no evidence to show a difference”
30:21Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025
Side effects and safety
It is a regular antihistamine and overly sedating in the daytime for most people, so we use it almost only at night, and it is not the first sleep aid we reach for.
“I think it's overly sedating for most people during the daytime. So I almost exclusively use it for nighttime dosing, but it's not the first one I reached for”
32:31Insomnia and Sleep Medications in PsychiatryDec 2024
Compared with others
A short-term sleeper can just as easily be high-dose hydroxyzine, low-dose trazodone, higher-dose gabapentin or, if you have to, mirtazapine.
“I think that what you're referring to can just as easily be accomplished by high dose hydroxyzine, low dose trazodone, gabapentin at higher doses, you know, Mirtazapine if you have to”
26:26Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026
It also comes up on
- AnxietyWhen the picture is likely trauma or personality and the diagnosis is still undifferentiated, start with smaller things (gabapentin, hydroxyzine, buspirone, propranolol) rather than serotonin-based medications, because of the risk of agitating an unrecognized bipolar disorder.
- Borderline personality disorderWhen the picture is likely trauma or personality and the diagnosis is undifferentiated, start with smaller things such as gabapentin, hydroxyzine, buspirone or propranolol, not serotonergic drugs, because of the risk of agitating a bipolar disorder.
- Generalized anxiety disorderMost of what you want from low-dose quetiapine in a non-psychotic disorder can be had with mirtazapine, gabapentin, buspirone or hydroxyzine.
- PTSDWhen the picture is likely trauma or personality and still undifferentiated, start with smaller things like gabapentin, hydroxyzine, buspirone or propranolol rather than serotonin-based drugs, because of the risk of agitating an unrecognized bipolar disorder.
- QuetiapineMost of what you want from low-dose quetiapine in a non-psychotic disorder you can get from mirtazapine, gabapentin, buspirone or hydroxyzine.
From these episodes
- Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026 · 1 point
- Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026 · 1 point
- Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 · 1 point
- Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 · 3 points
- PTSD Medications: Integrating Pharmacotherapy, Therapy, and the Treatment Frame | Episode 22Apr 2025 · 1 point
- Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 · 2 points
- Insomnia and Sleep Medications in PsychiatryDec 2024 · 2 points
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.