Last reviewed 2026-04-22 · How we verify

Trazodone HCl

Trazodone HCl is a serotonin antagonist and reuptake inhibitor (SARI) that blocks serotonin reuptake and antagonizes serotonin 2A receptors to elevate serotonin levels in the brain.

Trazodone HCl is a serotonin antagonist and reuptake inhibitor (SARI) that blocks serotonin reuptake and antagonizes serotonin 2A receptors to elevate serotonin levels in the brain. Used for Major depressive disorder, Insomnia (off-label use, particularly for sleep maintenance).

At a glance

Mechanism of action

Trazodone inhibits the reuptake of serotonin at the presynaptic membrane, increasing serotonin availability in the synaptic cleft. It also acts as an antagonist at serotonin 5-HT2A receptors, which contributes to its antidepressant and anxiolytic effects. This dual mechanism distinguishes it from selective serotonin reuptake inhibitors (SSRIs) and makes it particularly useful for depression with insomnia due to its sedating properties.

Approved indications

• Major depressive disorder
• Insomnia (off-label use, particularly for sleep maintenance)

Common side effects

• Sedation / drowsiness
• Dizziness
• Dry mouth
• Headache
• Orthostatic hypotension
• Priapism (rare)

Key clinical trials

• National Adaptive Trial for PTSD Related Insomnia (PHASE3)
• Comparing Digital Therapy, Trazodone, and Daridorexant for Menopause-Related Insomnia Symptoms (PHASE4)
• Trazodone and the Risk of Serious Adverse Events
• Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial (PHASE2, PHASE3)
• Standardized Sleep Bundle for Cardiac Surgery Patients (NA)
• Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants
• Real-world Clinical Response to Trazodone in Italy, Poland, and Romania
• A Cohort Study on Increasing Blood Pressure Benefits in Sleep Apnea Patients After CPAP Treatment

Primary sources

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