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trazodone (Desyrel, Pragmazone, Oleptro)

Tradename: Desyrel. (trazodone HCl) Indications: 1) depression 2) sleep disorder* 3) neurogenic pain 4) especially useful in patients for which anticholinergic effects would be problematic: a) elderly b) patients with benign prostatic hypertrophy * commonly used off-label to treat insomnia, but not much data to support use [10] Contraindications: - Caution: cardiac disease or arrhythmias - no evidence of cognitive benefit from trazodone vs other antidepressants in people with dementia [9] Dosage: 1) hypnotic: 50-100 mg QHS 2) start 50 mg PO TID 3) increase in 50 mg/day increments every 3-4 days 4) excessive sedation limits dose increase 5) maximum dose: 600 mg/day Tabs: 25, 50, 100, 150, 300 mg. Oleptro 150, 300 mg (extended-release) for depression [7] Pharmacokinetics: 1) oral bioavailability is 72-90%; take with snack to reduce nausea 2) extensively metabolized by the liver by cyt P450 2D6 -> active metabolite (1-m-chlorophenylpiperazine) is excreted in the urine 3) elimination 1/2life is 5-9 hours 4) maximal antidepressant effect occurs within 2-6 weeks 5) onset of action: 7 days Adverse effects: 1) common (> 10%) - dizziness, dry mouth, headache, nausea, bad taste in mouth, confusion, muscle tremors 2) less common (1-10%) - blurred vision, diarrhea, constipation, weakness 3) uncommon (< 1%) - prolonged priapism (1/6000), hypotension, rash, tachycardia, bradycardia, agitation, seizures, extrapyramidal effects, hepatitis, urinary retention 4) other - sedation (frequent) - postural hypotension (frequent) - irregular heartbeat - minimal anticholinergic effects - photosensitivity - in patients on hemodialysis, trazodone associated with higher risk of cardiovascular events [11] Drug interactions: 1) other CNS depressants: increase CNS depression 2) digoxin: increase in digoxin levels 3) phenytoin: increase phenytoin levels 4) MAO inhibitors: avoid combination 5) trazodone may interfere with antihypertensive effects of clonidine & methyldopa 6) trazodone may decrease effects of anticoagulants 7) fluoxetine increases trazodone levels 8) Ginkgo biloba in combination may cause CNS depression by overstimulation of GABA receptors [5] 9) coadministration with selective serotonin reuptake inhibitors SSRI may result in serotonin syndrome 10) any drug that inhibits cyt P450 2D6 may increase levels of trazodone Laboratory: 1) specimen: a) plasma (EDTA); stable for 2 months at -15 degrees C b) urine 2) methods: a) plasma: HPLC, GC b) urine: TLC Mechanism of action: 1) some effects similar to other antidepressants 2) serotonin-2 receptor inhibition 3) may inhibit reuptake of serotonin 4) inhibition of alpha adrenergic receptors

Interactions

drug interactions drug adverse effects (more general classes)

Related

1-m-chlorophenylpiperazine (MCPP) cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

General

piperazine pyridine second generation antidepressant

Properties

MISC-INFO: elimination route LIVER 1/2life 6-13 HOURS therapeutic-range 0.8-1.6 UG/ML protein-binding 89-95% elimination by hemodialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Prescriber's Letter 7(9):53 2000
  6. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  7. Prescriber's Letter 17(10): 2010 COMMENTARY: Oleptro (Trazodone) and Silenor (Doxepin) CHART: Comparison of Insomnia Treatments Detail-Document#: 261005 (subscription needed) http://www.prescribersletter.com
  8. Paauw DS Dangerous and Deadly Drug Combinations Medscape. June 30, 2016 http://www.medscape.com/features/slideshow/dangerous-drug-combinations
  9. Sommerlad A, Werbeloff N, Perera G et al. Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data. Int J Geriatr Psychiatry, 2021. September 25. PMID: 34564898 https://onlinelibrary.wiley.com/doi/abs/10.1002/gps.5625
  10. Monaco K Trazodone Commonly Used Off-Label for Insomnia. Not much data to support efficacy or safety "as a surrogate hypnotic medication," researcher says. MedPage Today September 20, 2022 https://www.medpagetoday.com/meetingcoverage/psychcongress/100819
  11. Mehrotra R et al Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis. A Randomized Clinical Trial. Ann Intern Med. 2024. Jan 16. PMID: 38224591 https://www.acpjournals.org/doi/10.7326/M23-1794