Serotonin antagonist and reuptake inhibitor (SARI) antidepressant
ATC code: N06AX05 (Trazodone)
Brand names
Desyrel, Trittico, Oleptro
A 5-HT2A serotonin receptor antagonist with concurrent (moderate) serotonin reuptake inhibition. Also blocks α1-adrenoreceptors and H1 histamine receptors – the source of marked sedation. Low doses (25–100 mg at bedtime) feature 5-HT2A and H1 blockade, producing hypnotic effect. Higher doses (150–400 mg/day) unfold antidepressant action. Half-life 5–9 hours.
Second line
Second-line for major depressive disorder, particularly with concurrent insomnia and anxiety. NG222 (2022) and 2024 set SSRIs and SNRIs (sertraline, escitalopram, venlafaxine) as first-line. Trazodone is used when sedation is desired, at 150–400 mg/day with titration over 2 weeks. Not preferred due to marked sedation and orthostatic hypotension risk.
Adjunct
Used off-label at low doses 25–100 mg at bedtime for insomnia, especially with concurrent depression or anxiety. 2017 sets CBT-I as first-line for chronic insomnia; pharmacotherapy applies when CBT-I is unavailable or ineffective. Trazodone is not preferred (WEAK recommendation against) – evidence is limited and orthostatic hypotension and morning sedation are concerns.
Off-label use, widely employed in Spain and the US.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Trazodone is a serotonergic antidepressant that in the US and several other countries is most often prescribed as a sleep aid at low doses (25-100 mg at bedtime), rather than as an antidepressant. International insomnia guidelines ( 2017, NG219) do not recommend trazodone as first-line for chronic insomnia in people without depression. A Cochrane meta-analysis (Yi 2018) in patients with major depression did not confirm trazodone's advantages over other antidepressants. The drug has specific risks: orthostatic hypotension (especially in older adults, with fall risk), priapism (a prolonged, painful erection requiring emergency care), and next-day sedation. The foundation of insomnia treatment is cognitive-behavioral therapy for insomnia (CBT-I); first-line medications include melatonin and, when indicated, benzodiazepine receptor agonists or orexin antagonists. If trazodone was prescribed for sleep, consider seeking a second opinion.
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Boxed warning
FDA boxed warning: antidepressants increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults under 24 during the first weeks of treatment. Careful monitoring of mental status is needed, especially at initiation and dose change.
FDA category C. Limited pregnancy data. SSRIs with more data (sertraline) are preferred in depressed pregnant patients. T3 use is linked to neonatal withdrawal.
Trazodone is evaluated for the following indications with varying evidence strength: Major depressive disorder (evidence tier B), Chronic insomnia in adults under 55 (evidence tier C), Insomnia and sleep disorders (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Trazodone (≥ 1 in 100): Drowsiness, daytime sedation, Dizziness, Orthostatic hypotension, Dry mouth, Fatigue, Nausea. See the Safety section for uncommon and serious reactions.
FDA category C. FDA category C. Limited pregnancy data. SSRIs with more data (sertraline) are preferred in depressed pregnant patients. T3 use is linked to neonatal withdrawal.
Milk concentrations are low. Acceptable when needed, with monitoring of infant sedation and weight gain.
Trazodone is contraindicated in: Trazodone hypersensitivity; Acute alcohol or hypnotic intoxication; Acute myocardial infarction; Severe hepatic impairment; Concurrent MAO inhibitors or within 14 days of stopping them. Full list in the Safety section.
Milk concentrations are low. Acceptable when needed, with monitoring of infant sedation and weight gain.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
FDA boxed warning: antidepressants increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults under 24 during the first weeks of treatment. Careful monitoring of mental status is needed, especially at initiation and dose change.