Serotonin antagonist and reuptake inhibitor (SARI)
Inhibits serotonin reuptake and antagonizes 5-HT2A receptors; also blocks histamine H1 and alpha-1 adrenergic receptors, contributing to sedative and hypotensive effects
Major depressive disorder (MDD)
Insomnia (sleep onset and maintenance), agitation and behavioral disturbances in dementia
Oral tablets (50 mg, 100 mg, 150 mg, 300 mg; immediate and extended-release)
25–50 mg p.o. nightly for sleep or agitation; may be titrated up to 150–400 mg/day for depression
150–400 mg/day for MDD; 25–150 mg/night for insomnia or behavioral symptoms
Half-life ~6–11 hours; metabolized via CYP3A4; active metabolite (mCPP) may contribute to serotonergic effects
Sedation, dizziness, dry mouth, orthostatic hypotension, headache, blurred vision
Priapism, QTc prolongation, cardiac arrhythmia, serotonin syndrome (with other serotonergic agents)
Monitor for orthostatic hypotension, ECG in patients with cardiovascular risk, and signs of priapism or serotonin syndrome
Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders
Trazodone is frequently used off-label in older adults with dementia for insomnia and agitation, though its sedating and hypotensive effects increase fall risk. It may also be beneficial in managing sleep disturbances and behavioral symptoms in patients with post-stroke conditions or traumatic brain injury (TBI). In individuals with cardiovascular disease, use caution due to the potential for orthostatic hypotension and QTc prolongation. Combining trazodone with other central nervous system (CNS) depressants should be avoided unless clinically necessary.