Trazodone is a first-line, non-habit-forming sleep medication: long lasting, good for sleep maintenance, kind to sleep architecture, and helpful for nightmares. Start very low and early in the evening, warn that a minority get agitation or worse sleep (likely from its mCPP metabolite), and remember low-dose trazodone is not a small antidepressant.
When we reach for it
On day one, the first-line sleepers are the non-habit-forming ones that support deep, healthy sleep: trazodone and gabapentin, with hydroxyzine a fair choice too. These are broadly applicable for sleep in most to all disorders. Avoid anticholinergics like Benadryl if you can.
“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 Also said in 2 more episodes
“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 “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 It is often the first one we reach for, because it has additional effects: nightmare suppression in trauma disorders, and anxiety to some extent.
“The first one I reached for is Trazodone because it's got a lot of additional effects. In my opinion, it's effective also for things like nightmare suppression and trauma disorders and anxiety to some extent”
32:40Insomnia and Sleep Medications in PsychiatryDec 2024
Dosing and titration
Start incredibly low, half of a 50 mg tablet, and take it one or two hours before the desired bedtime, because onset is slow. It is long lasting and good for sleep maintenance.
“It's long lasting. Good for sleep maintenance. Now the time to onset isn't great. So you do have to take it on like a timer, you know, one or two hours before your desired bedtime”
25:22Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026 Also said in 1 more episode
“I actually start incredibly low. I start at half a tablet of the 50 milligrams most of the time and have people try that. And I tell them to take it one or two hours before their desired bedtime”
33:09Insomnia and Sleep Medications in PsychiatryDec 2024 If someone is not very sensitive to it, it can go to 200 mg and beyond, and then it is an antidepressant too.
“Additionally, if they're not very sensitive to trazodone, they can take a very high dose. I can take it up to 200 plus, and now it's an antidepressant too”
38:37Insomnia and Sleep Medications in PsychiatryDec 2024
Side effects and safety
Its active metabolite, mCPP, can cause agitation and dysphoria, and some people get agitated even at low doses. If you see real agitation, do not keep adjusting it.
“Trazodone has an active metabolite. Called MCPP. Okay. Metachlorophenylpipirazine, which is apparently like a designer drug that causes agitation and dysphoria, but also may have antidepressant effects”
24:40Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026 Also said in 1 more episode
“Trazodone does have an active metabolite that can be agitating. So some people, for whatever reason, seem to respond to Trazodone even at lower doses of agitation. Don't try to play around further with it if you're getting actual agitation on Trazodone”
35:20PTSD Medications: Integrating Pharmacotherapy, Therapy, and the Treatment Frame | Episode 22Apr 2025 In bipolar disorder, be wary and careful above 150 mg.
“I do get wary and careful if we're going to TRASM above 150 in bipolar disorder or if we're doing mirtazapine above 15 or 20-ish”
47:26Insomnia and Sleep Medications in PsychiatryDec 2024
Compared with others
Eight hours of slightly modified sleep architecture beats five hours of terrible sleep. But if a patient could get nine hours and is staying up on their phone, why mess with their sleep architecture at all?
“Eight hours of a slightly modified sleep architecture is better than five hours of a terrible sleep architecture. But that said, if a patient could be getting nine hours, but they're staying up because they're on their phone, then why should we mess with their sleep architecture”
26:49Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026
Pitfalls and myths
Low-dose trazodone is not a small antidepressant. At 50 mg it is not reuptaking serotonin, which is its antidepressant mechanism, so you have to reach higher doses for that.
“Low-dose trazodone is not a small antidepressant. So it is one of those medications that you need to get it to the higher doses”
55:31Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 Also said in 1 more episode
“when you're using trazodone at the lower doses, don't think of it as a mild antidepressant. Like at 50 milligrams, it's not reuptaking serotonin, which is its antidepressant mechanism”
39:06Insomnia and Sleep Medications in PsychiatryDec 2024
Talking to patients
Say: this works great for a lot of people, and for some it does not work at all and might even make sleep worse. We do not know which you are, so try it. A small share do have that paradoxical reaction.
“I pretty much say, hey, this works great for a lot of people. And for some people, it doesn't work at all and might even make the sleep worse. We don't know. Why don't you just try it out”
56:51Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 Also said in 1 more episode
“In my experience, I do see a small proportion of patients have like a paradoxical reaction. where it, I think you mentioned that, like where it makes it more difficult to sleep”
35:07Insomnia and Sleep Medications in PsychiatryDec 2024
It also comes up on
- AntipsychoticsIn the ICU or nursing home, controlling the sleep-wake cycle with trazodone, mirtazapine, melatonin or ramelteon may give a lot of the same effect without the same problems.
- InsomniaIn the ICU or nursing home, controlling the sleep-wake cycle with trazodone, mirtazapine, melatonin or ramelteon may give a lot of the same effect without the same problems.
- BenzodiazepinesA short-term sleeper can just as easily be high-dose hydroxyzine, low-dose trazodone, higher-dose gabapentin, or mirtazapine if you have to.
- Bipolar disorderThe mood stabilizers with antidepressant efficacy are the 'three Ls and a Q': in the discussion, lithium, lamotrigine, trazodone and quetiapine.
- DementiaIn the nursing home or ICU patient, controlling the sleep-wake cycle with something like trazodone, mirtazapine, melatonin or ramelteon may give a lot of the same effect without the same problems.
- HydroxyzineA short-term sleeper can just as easily be high-dose hydroxyzine, low-dose trazodone, higher-dose gabapentin or, if you have to, mirtazapine.
- InsomniaA one-week benzodiazepine can get someone through an acute crisis that is partly depression, though the same can just as easily be done with high-dose hydroxyzine, low-dose trazodone, higher-dose gabapentin or, if needed, mirtazapine.
- LamotrigineIt is one of the mood stabilizers with antidepressant efficacy, the 'three Ls and a Q', named here as lithium, lamotrigine, trazodone and quetiapine.
From these episodes
- Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026 · 3 points
- Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 · 2 points
- PTSD Medications: Integrating Pharmacotherapy, Therapy, and the Treatment Frame | Episode 22Apr 2025 · 2 points
- Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 · 1 point
- Insomnia and Sleep Medications in PsychiatryDec 2024 · 7 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.