Pharm

Trazodone

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Trazodone, Desyrel, Oleptro

  • See Also
  1. Serotonin Antagonist and Reuptake Inhibitor (SARI)
  • Indications
  1. Major Depression (largely replaced by SSRI and SNRI agents)
  2. Aggressive Behavior (off label)
  3. Cocaine Withdrawal (off label)
  4. Erectile Dysfunction
    1. See Erectile Dysfunction Management for more effective agents
  5. Insomnia
    1. Not recommended due to low efficacy and adverse effects including Fall Risk
    2. Sateia (2017) J Clin Sleep Med 13(2): 307-49 [PubMed]
  • Mechanism
  1. Triazolopyridine derivative
  2. Unrelated to Tricyclic Antidepressants
  3. Phenylpiperazine Antidepressant (Serzone prototype)
  4. Serotonin Antagonist and Reuptake Inhibitor (SARI)
    1. Blocks 5-HT-2 postsynaptic receptor
    2. Low dose: Serotonin receptor Antagonist
    3. High dose: Serotonin Agonist
    4. Weaker than SSRIs as a Serotonin reuptake inhibitor
  • Pharmacokinetics
  1. Serum Half Life: 4 to 9 hours
  2. Therapeutic plasma level: 800 to 1600
  3. Well absorbed
  4. Extensive hepatic metabolism
  • Safety
  1. Pregnancy Category C
  2. Avoid in Lactation
  • Efficacy
  1. Major Depression
    1. As effective as Fluoxetine, Tricyclic Antidepressants
  2. Insomnia
    1. Decreases nightly awakenings
    2. Slight improvement on sleep quality
    3. Does NOT increase sleep time, Sleep Efficiency, Sleep Latency or waking time after sleep onset
    4. References
      1. Yi (2018) Sleep Med 45:25-32 [PubMed]
      2. Everitt (2018) Cochrane Database Syst Rev (5): CD010753 [PubMed]
  • Background
  1. Generic Drug
  • Dosing
  1. Insomnia
    1. Dose: 50 mg orally at bedtime
    2. Range: 25-100 mg orally at bedtime
    3. Maximum: 150 mg orally at bedtime
  2. Major Depression
    1. Start: 50 to 150 mg per day in divided doses
    2. Effective dose: 400 to 600 mg in divided doses
  • Adverse Effects
  1. Sedation
    1. Limits use as an Antidepressant
    2. Useful in Major Depression with Insomnia
  2. Priapism
    1. See Priapism Management
  3. Serotonin Syndrome
  4. Cardiac Arrhythmia
  5. Decreased Appetite
  6. Orthostatic Hypotension (Dizziness)
    1. Minimize by administering with food
  7. Fall Risk
    1. Increased risk of falls when used for Insomnia
    2. Fall Risk is higher with Trazodone than with Zolpidem or Benzodiazepines
    3. Amari (2022) Adv Ther 39(3): 1324-40 [PubMed]
  • Drug Interaction
  1. Metabolized by CYP3A4 and CYP2D6
  2. Increased serum Digoxin level
  3. Increased Phenytoin level
  • Toxicity
  1. Less toxic in Overdose than Tricyclic Antidepressants
  2. Lower Incidence of Anticholinergic Toxicity
  • Resources
  1. Trazodone (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=17b3356e-458d-47f6-89a5-80828ab48d4c
  • References
  1. (2023) Med Lett Drugs Ther 62(1592): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 38-9
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  4. Sundberg (1995) Depression Primary Care, PGM, p. 45-57