ROUTE OF ADMINISTRATION: Oral (well absorbed)
PEAK BLOOD LEVELS: 1-2 hours after dosing
PROTEIN BINDING: 89-95%
HALF-LIFE: 7-10 hours
METABOLISM: Liver. CYP2D6 and CYP3A4. Metabolized to an active metabolite. Trazodone induces P-glycoprotein.
STARTING DOSE: 50mg-100mg
BEST TIME TO DOSE: Bedtime
HOW TO DOSE: Initial 50mg-100mg at bedtime for 4-7 days then increase by 50mg-100mg every day until response occurs (for depression, typically 300mg-400mg per day). Max dose 600mg/day.
PREGNANCY: Minimal Safety Data. Consider discontinuing.
BREASTFEEDING: Minimal Safety Data. Consider discontinuing.
Priapism, orthostatic hypotension, drowsiness, fatigue, dizziness, dry mouth, nausea, acid reflux, upset stomach, headaches, restlessness
- Major Depressive Disorder
Off Label Uses: Insomnia, Anxiety
Mechanism(s) of Action
Trazodone is considered a Serotonin Antagonist and Reuptake Inhibitor (SARI) with the following properties:
- Antagonist actions at 5HT2A and 5HT2C receptors
- Weak inhibitor of serotonin transporter (SERT)
- Partial agonist at 5HT1A receptors
- Antagonist actions at H1 receptors
- Antagonist actions at postsynaptic α1 receptors
- Different doses of Trazodone have different properties: At low doses, there is prominent 5-HT2A receptor antagonist, H1 antagonism, and α1-adrenergic antagonism and minimal SERT or 5-HT2C inhibition properties. At higher doses, there is increasing 5-HT2A inhibition , 5HT2C inhibition , and SERT inhibition. Trazodone was never a great antidepressant due to sedation. Trazodone has minimal anticholinergic properties (good for elderly). Trazodone may cause Orthostatic hypotension due to alpha-1 blockade. Hypnotic effects are not due to anticholinergic activity or antihistaminergic activity.
- Studies suggest that trazodone increases slow wave sleep with minimal effects on sleep architecture
- Trazodone is probably a better anxiolytic than antidepressant
- Patients taking trazodone may test positive on urine tests for the presence of MDMA or “ecstasy.”
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