Trazodone (for sleep)
Sedating antidepressant used off-label at low doses (25-100 mg) as one of the most commonly prescribed non-controlled hypnotics. Improves sleep continuity without dependence, but carries next-day sedation, orthostatic hypotension, and the rare but serious risk of priapism in men.
01 Overview
Trazodone is a serotonin antagonist and reuptake inhibitor (SARI) approved as an antidepressant at 150-600 mg, but by far its most common real-world use is off-label at low doses (25-100 mg) for insomnia. Despite thin regulatory backing for this indication, it is among the most frequently prescribed sleep agents in the US, largely because it is non-scheduled and not habit-forming.
At hypnotic doses its sedation derives chiefly from H1 antihistamine and 5-HT2A/alpha-1 adrenergic blockade. It improves sleep continuity and is often chosen for patients with comorbid depression or a history of substance use. Trade-offs include next-morning grogginess, orthostatic hypotension and falls (especially in the elderly), and the uncommon but urological-emergency risk of priapism.
02 Mechanism
At low doses, sedation arises from antagonism of histamine H1, serotonin 5-HT2A, and alpha-1 adrenergic receptors; at higher doses it also inhibits serotonin reuptake (antidepressant effect).
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Sleep (off-label) | 25–100 mg/day | Oral | 25-100 mg at bedtime; start low. Antidepressant dosing is much higher (150-600 mg). |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved sleep continuityReduces awakenings and improves subjective sleep quality; preserves slow-wave sleep. | Clinical | ||
| No dependence / suitable with SUD historyNon-scheduled and non-reinforcing, making it a preferred option where controlled hypnotics are undesirable. | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Next-day sedation / grogginessResidual drowsiness and impaired alertness in the morning. | Moderate | Common | Clinical | |
| Orthostatic hypotension / fallsDizziness and blood-pressure drops on standing, raising fall risk. | Moderate | Common, especially elderly | Clinical | |
| PriapismProlonged, painful erection that is a urological emergency and can cause permanent damage. | Severe | Rare (~1 in several thousand men) | Clinical |