Contents
Clinical Information
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-100mgÂ
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.
Side Effects
Priapism, orthostatic hypotension, drowsiness, fatigue, dizziness, dry mouth, nausea, acid reflux, upset stomach, headaches, restlessness
FDA Indications
- 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.Â
Additional Information
- 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.”
References
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- Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
- Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
- J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
- Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
- Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
- Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
- Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
- Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.