Trazodone
Trazodone is an atypical antidepressant from the SARI class (serotonin antagonist and reuptake inhibitor). It is FDA-approved for major depression at higher doses but is far more commonly prescribed at low dose (25–100mg at bedtime) for chronic insomnia, where its sedating profile makes it useful.
- Chemical formula
- C19H22ClN5O
- CAS number
- 19794-93-5
- ATC code
- N06AX05
- Molecular weight
- 371.86 g/mol
- Drug class
- Atypical antidepressant / serotonin modulator
- Also known as
- Desyrel, Oleptro, Trittico
What is it?
Trazodone is an atypical antidepressant introduced in 1981, marketed historically as Desyrel and as Oleptro (extended-release) and Trittico (Europe). Authorised generic trazodone has dominated the market for decades and is widely available. Despite the antidepressant approval, contemporary use is dominated by off-label prescribing of low doses (25–100mg at bedtime) for chronic insomnia, where the sedating profile combined with relative safety in long-term use has made it one of the most commonly prescribed sleep aids.
Mechanism of action
Trazodone is classified as a serotonin antagonist and reuptake inhibitor (SARI). It blocks 5-HT2A receptors and weakly inhibits the serotonin reuptake transporter, while also producing strong antagonism at H1 histamine and α1-adrenergic receptors. The antihistamine and α1-blocking activity dominate at low doses, producing sedation; antidepressant effect requires higher doses (150–300mg/day) where serotonergic activity becomes meaningful.
Pharmacokinetics
Trazodone is well absorbed orally with peak plasma at 1 hour (immediate-release) or 9 hours (extended-release Oleptro). The terminal half-life of immediate-release is 5–9 hours, supporting once-nightly dosing for sleep. Hepatic metabolism via CYP3A4 produces the active metabolite mCPP, which contributes to anxiogenic effects in some users. Strong CYP3A4 inhibitors and inducers can substantially alter trazodone exposure.
Indications
Trazodone is approved for major depressive disorder. It is widely used off-label for insomnia (most common modern use), depression with anxiety, post-traumatic stress disorder, and adjunctive use with SSRIs for sleep. According to current sleep guidelines, low-dose trazodone is one of several options for chronic insomnia, particularly when standard hypnotics (zolpidem, eszopiclone) are unsuitable due to dependence concerns.
Safety profile
Common adverse effects are sedation (the desired effect at low doses), dry mouth, dizziness, orthostatic hypotension and headache. The most distinctive adverse event is priapism (rare but serious — caused by α1-adrenergic blockade), which warrants immediate medical attention if it occurs. QT prolongation is a class concern at higher antidepressant doses. According to current guidelines, trazodone has a benign tolerance and dependence profile compared with benzodiazepines and Z-drugs.
Products containing this ingredient
Frequently asked questions
Why is trazodone used for sleep instead of as an antidepressant? ▾
At low doses (25–100mg), trazodone's H1 antihistamine and α1-blocking effects dominate, producing sedation without significant antidepressant activity. Antidepressant doses (150–300mg) cause too much daytime sedation and orthostatic effects for routine use. According to clinical practice, low-dose bedtime trazodone is one of the most commonly prescribed sleep aids in the United States, especially when chronic use is anticipated.
Is trazodone addictive? ▾
Trazodone has minimal abuse liability and does not produce tolerance or dependence with chronic use, unlike benzodiazepines and Z-drugs. According to current guidelines, this makes it a preferred option for chronic insomnia where long-term hypnotic use is anticipated. Discontinuation does not produce withdrawal at typical sleep doses.
What should I do if priapism occurs with trazodone? ▾
Priapism (an erection lasting more than 4 hours) is a rare but serious adverse effect of trazodone caused by α1-adrenergic blockade. It requires immediate medical attention because prolonged engorgement can damage cavernosal tissue. According to the prescribing information, men starting trazodone should be counselled about this possibility and instructed to seek emergency care if it occurs.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.