Trazodone (Desyrel)


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

starting dose:
> 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.
FDA Indications:
1) Major Depressive Disorder

 

ADDITIONAL INFORMATION

 

  • 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.”

Mechanism of 5HT2C Antagonism:

REFERENCES:

  1. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  2. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  3. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  4. 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.
  5. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  6. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  7. Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  8. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  9. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.

(Note: the diagrams were created by me, but the theories behind them were taken from numerous textbooks and articles. For more information, I recommend Dr. Stephen Stahl’s Textbook “Stahl’s Essential Psychopharmacology” 4th edition).

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