Pharmacology · Atypical antidepressants
Trazodone !
An antidepressant that blocks 5-HT2A receptors and weakly blocks serotonin reuptake. Very sedating, often used for sleep; can cause priapism.
Updated 2026-11-01
Mechanism of action
Trazodone blocks 5-HT2A receptors and, more weakly, the serotonin transporter, and is a partial agonist at 5-HT1A receptors. It also blocks alpha-1 adrenergic and H1 receptors, explaining its sedation and orthostatic hypotension. Its metabolite m-chlorophenylpiperazine (mCPP) is also active.
- Trazodone blocks 5-HT2A receptors
- It weakly blocks serotonin reuptake
- H1 and alpha-1 block cause sleepiness and low blood pressure
- Mood and sleep improve
Pharmacokinetics
- Absorption
- By mouth; tablets can be split along the score line but are not chewed or crushed
- Metabolism
- CYP3A4 forms the active metabolite mCPP; strong CYP3A4 inhibitors raise trazodone levels
Indications
- Major depressive disorder
- Sometimes used for insomnia (off-label)
Adverse effects
Common
- Sleepiness and fatigue
- Dizziness and orthostatic hypotension
- Dry mouth, nausea
- Headache, blurred vision
Contraindications
- MAO inhibitors, or within 14 days of stopping one; not started during linezolid or intravenous methylene blue
- Avoided with known QT prolongation or a history of arrhythmias
Key interactions
- Strong CYP3A4 inhibitors (clarithromycin, itraconazole, voriconazole)
- Higher trazodone levels, more sedation and arrhythmia risk
- CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John's wort)
- Lower trazodone levels
- Other QT-prolonging drugs (class IA and III antiarrhythmics, some antipsychotics)
- Additive arrhythmia risk
- Alcohol and other CNS depressants
- Additive sedation
- Other serotonergic drugs
- Serotonin syndrome
What is monitored
- Orthostatic blood pressure and falls
- ECG with heart disease or other QT-prolonging drugs
- Mood and suicidal thoughts
- Sleepiness the next morning
Administration and safety
- Given by mouth; drowsiness may lead to giving most of the daily amount at bedtime
- Tablets may be split on the score line; not chewed or crushed
- Stopped gradually
Nursing care
- Teach men that an erection lasting more than four hours is an emergency that needs urgent care
- Check orthostatic blood pressure and teach to rise slowly; fall precautions in older adults
- Warn about drowsiness, driving and alcohol
- Assess suicidal thoughts early in treatment
Pregnancy and breastfeeding
Decades of published human data have not identified a drug-related risk of major birth defects or miscarriage.
Test yourself
Think of the answer, then tap the question to see it.
Which antidepressant is classically linked to priapism?
Trazodone. A prolonged erection can permanently damage erectile tissue and needs emergency care.
Why is trazodone often used at night?
Its H1 and alpha-1 blockade causes marked sedation, which is why it is also used for insomnia.
Why can clarithromycin increase the cardiac risk of trazodone?
Clarithromycin is a strong CYP3A4 inhibitor, so trazodone levels rise, and both drugs can prolong the QT interval.
Related drugs
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - TRAZODONE HYDROCHLORIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); Trazodone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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