Section 10 · Monograph

Trazodone

Reviewed Nov 2026FDA label

Desyrel / genericSerotonin antagonist/reuptake inhibitor

Black Box Warning

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults (ages 18-24) with MDD and other psychiatric disorders.
This risk must be weighed against clinical need; short-term studies did not show increased suicidality risk with antidepressants vs. placebo in adults beyond age 24, and showed a reduction in risk in patients aged 65 and older.
All patients started on trazodone should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and at times of dose changes.
Trazodone is not approved for use in pediatric patients.

Treatment of major depressive disorder (MDD) in adults (FDA-approved).FDA-labeled

Off-label treatment of insomnia (sleep-onset and sleep-maintenance) at low doses, typically 25-100 mg at bedtime — one of the most commonly prescribed off-label agents for insomnia in US practice, favored for its non-controlled status, low cost, and low abuse potential relative to benzodiazepine receptor agonists.Off-label
Despite widespread use, the 2017 American Academy of Sleep Medicine (AASM) Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults issued only a WEAK recommendation AGAINST using trazodone for sleep-onset or sleep-maintenance insomnia, citing low-quality evidence and uncertainty that benefits outweigh harms (sedation hangover, orthostasis, falls, rare cardiac/priapism risk).Off-label
Off-label adjunct for insomnia secondary to SSRI/SNRI activation ('trazodone for sleep' add-on) and for insomnia in patients with comorbid depression.Off-label

Trazodone is a triazolopyridine/phenylpiperazine-derivative antidepressant classified as a serotonin antagonist and reuptake inhibitor (SARI).
Weakly inhibits presynaptic neuronal serotonin reuptake and is a potent antagonist at postsynaptic 5-HT2A and 5-HT2C receptors; also antagonizes histamine H1 receptors (sedation) and peripheral alpha-1 adrenergic receptors (orthostatic hypotension, priapism risk).
At low doses (25-100 mg) used off-label for insomnia, H1-antihistaminergic and 5-HT2A-antagonist sedative-hypnotic effects predominate, whereas antidepressant efficacy requires higher serotonin-reuptake-inhibiting doses (≥150 mg).
The active metabolite meta-chlorophenylpiperazine (mCPP) contributes to some adverse effects (anxiety, headache).

Depression (FDA-approved): Initiate 150 mg/day in divided doses; may increase by 50 mg/day every 3-4 days as tolerated. Usual effective outpatient range 150-400 mg/day; hospitalized patients may require up to 600 mg/day in divided doses. Take shortly after a meal/light snack.
Insomnia (off-label): typical starting dose 25-50 mg at bedtime; may titrate up to a common practical ceiling of 100 mg qHS; doses above ~100 mg used for sleep confer little additional hypnotic benefit while increasing next-day sedation, orthostasis, and arrhythmia/QT risk.
Elderly: start at the low end (12.5-25 mg qHS for insomnia); increased sensitivity to orthostatic hypotension, falls, and sedation.
Discontinuation: gradual dose reduction is reasonable practice after longer-term or higher-dose use to minimize rebound insomnia.

Hepatic/renal impairment: no formal FDA dose-adjustment schedule provided; use caution, start low, titrate slowly.

Known hypersensitivity to trazodone hydrochloride or any formulation component.
Concomitant use with monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing an MAOI — risk of serotonin syndrome.
Concomitant use with linezolid or intravenous methylene blue unless emergency circumstances require it, with close monitoring.
Use is not recommended during the initial recovery phase following myocardial infarction.

MAOIs — contraindicated; risk of serotonin syndrome.
Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) markedly increase trazodone exposure — reduce dose.
Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's Wort) decrease trazodone exposure.
Other serotonergic drugs — additive serotonin syndrome risk.
CNS depressants (alcohol, benzodiazepines, barbiturates, opioids) — additive sedation.
Warfarin/antiplatelets/NSAIDs — increased bleeding risk; monitor INR.
Digoxin and phenytoin — trazodone may increase serum concentrations; monitor levels.
QT-prolonging drugs — additive QT risk.

Very common: somnolence/sedation, dizziness, dry mouth, blurred vision, headache, nausea, orthostatic hypotension/syncope.
Common: constipation, fatigue, nervousness, edema, weight change.
Serious: priapism (painful erection >4-6 hours) — rare but a medical emergency requiring immediate discontinuation and urologic evaluation.
Cardiac: QT/QTc prolongation, torsade de pointes, and ventricular arrhythmias reported even at doses ≤100 mg/day.
Serotonin syndrome, activation of mania/hypomania, hyponatremia/SIADH (particularly in elderly), rare hepatotoxicity, rare leukopenia/neutropenia, suicidality.

Mental status, mood, and suicidality — especially during the first several months and after dose changes.
Orthostatic vital signs, particularly at initiation and in elderly patients.
ECG/QTc in patients with cardiac disease, electrolyte abnormalities, or concomitant QT-prolonging drugs.
Serum sodium in elderly patients.
INR if on warfarin; digoxin/phenytoin levels if co-administered.
Screen for personal/family history of bipolar disorder before initiating.
For off-label insomnia use: assess next-day sedation, driving/psychomotor impairment, and fall risk.

Pregnancy: No adequate well-controlled human trials. Available registry/epidemiologic data have not shown a clear increase in major malformations. Third-trimester exposure carries a risk of poor neonatal adaptation syndrome. A National Pregnancy Registry for Antidepressants is available (1-844-405-6185).
Lactation: Trazodone and its active metabolite are excreted into human milk at low levels; monitor breastfed infants for sedation and poor feeding.