Trazodone
Desyrel · Raldesy
Serotonin Antagonist and Reuptake InhibitorGeneric availableTDM data
The mechanism of trazodone's antidepressant action is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS. Trazodone is both a selective serotonin reuptake inhibitor (SSRI) and a 5HT2 receptor antagonist and the net result of this action on serotonergic transmission and its role in trazodone's antidepressant effect is unknown.
Compare Trazodone →FDA-Approved Indications
- Major depressive disorder (adults)
Common Off-Label Uses
- Insomnia
- Anxiety disorders (adjunct)
- Agitation in dementia
- SSRI-induced sexual dysfunction
What Sets This Drug Apart
- Bifunctional mechanism: at low doses (25-100 mg) acts primarily as H1/alpha-1 antagonist (sedative-hypnotic); at antidepressant doses (150-400 mg) adds meaningful SERT inhibition
- Mostly used off-label as a hypnotic at low doses despite FDA approval only for MDD — one of the most prescribed sleep aids in the US
- Priapism risk is rare but serious (~1 per 6,000 men); FDA-labeled concern requiring patient counseling and immediate urologic evaluation if it occurs
- No abuse potential or dependence liability — advantage over benzodiazepines and z-drugs for insomnia
- Short half-life (5-9h) limits hangover but makes it suboptimal for sleep maintenance; sustained-release formulation (Oleptro) extends effect
Boxed Warning
WARNING: SUICIDAL THOUGHTS and BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult