Route of Administration: Oral (well absorbed)
Peak blood levels: 1-2 hours after dosing
Protein Binding: 89-95%
Bioavailability is Not influenced by age or food
half-life: 7-10 hours
Extensive Hepatic Metabolism: 2D6, 3A4
> IR: 50mg PO TID
> ER: 150mg PO QHS
best time to dose: Morning
how to dose:
> IR: Initial 50mg PO TID for 1 week. Increase by 50mg per day every
week until response (for depression, typically 300mg-400mg per day).
Max dose 600mg/day.
> ER: Initial 150mg PO QHS for 1 week. Increase by 75mg/day every 3 days.
Max dose 375mg/day.
pregnancy: Minimal Safety Data. Consider discontinuing.
breastfeeding: Minimal Safety Data. Consider discontinuing.
1) Major Depressive Disorder
- Trazodone is considered a Serotonin Antagonist and Reuptake Inhibitor (SARI) with the following properties:
- Antagonist actions at 5HT2A and 5HT2C
- 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:
- 5-HT2A receptor antagonist, H1 antagonism, and α1-adrenergic antagonism
- Minimal SERT or 5-HT2C inhibition properties
At high Doses:
- 5-HT2A inhibition
- 5HT2C inhibition
- SERT inhibition
- Trazodone was never a great antidepressant due to sedation
- Questionable efficacy for depression at doses <375mg/day.
- Interestingly, hypnotic effects are not due to anticholinergic and probably not antihistaminergic effects.
- Trazodone is often used for insomnia.
- Studies suggest that trazodone increases slow wave sleep with minimal effects on sleep architecture
- Trazodone is probably a better anxiolytic than antidepressant
- Trazodone has minimal anticholinergic properties (good for elderly)
- Trazodone may cause Orthostatic hypotension due to alpha-1 blockade
- Trazodone increases the risk of priapism (Trazo-BONE).
- Metabolized primarily through CYP3A4 to active metabolite.
- Trazodone induces P-glycoprotein
- Patients taking trazodone may test positive on urine tests for the presence of MDMA or “ecstasy.”
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