BSN Tracker

trazodone

Brand: Desyrel, Oleptro

⚠ BBW Beers Criteria Prototype Drug
Drug Class: serotonin antagonist and reuptake inhibitor (SARI)
Drug Family: antidepressant
Subclass: triazolopyridine antidepressant
Organ Systems: cns

Mechanism of Action

Inhibits serotonin reuptake (weak) and potently antagonizes 5-HT2A receptors, alpha-1 adrenergic receptors, and histamine H1 receptors. The combination of weak SERT inhibition and 5-HT2A blockade produces antidepressant and anxiolytic effects with a favorable sexual side effect profile.

SERT (serotonin transporter)5-HT2A receptoralpha-1 adrenergic receptorH1 histamine receptor

Indications

  • major depressive disorder
  • off-label: insomnia (most common use at low doses)
  • off-label: anxiety
  • off-label: fibromyalgia pain

Contraindications

  • concurrent MAOI use
  • congenital or acquired long QT syndrome

Adverse Effects

Common

  • sedation
  • dizziness
  • dry mouth
  • blurred vision
  • orthostatic hypotension
  • headache

Serious

  • priapism (rare; urological emergency)
  • QT prolongation
  • serotonin syndrome
  • suicidal ideation
  • orthostatic hypotension with falls (elderly)

Pharmacokinetics (ADME)

Absorption well absorbed orally; bioavailability ~65%; food enhances absorption and reduces peak concentration variability
Distribution protein binding ~89-95%; Vd ~0.8-1.5 L/kg
Metabolism extensively hepatic via CYP3A4; active metabolite m-chlorophenylpiperazine (mCPP) has serotonergic activity
Excretion primarily renal; clearance may be reduced in elderly
Half-life 3-9 hours (immediate release); 10 hours (extended release)
Onset sleep-promoting effect within first dose; antidepressant effect 2-4 weeks
Peak 1-2 hours (fasting); 2-3 hours (with food)
Duration 8-12 hours (IR)
Protein Binding 89-95%
Vd 0.8-1.5 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
MAOIs serotonin syndrome contraindicated
CYP3A4 inhibitors (ketoconazole, ritonavir) increased trazodone levels and QT risk major
antihypertensives additive hypotension via alpha-1 blockade moderate
digoxin may increase digoxin levels moderate

Nursing Considerations

  1. Priapism is a rare but serious adverse effect requiring emergency urological intervention within 4-6 hours; instruct male patients to seek immediate care for prolonged erection (>4 hours).
  2. Assess orthostatic blood pressure in elderly patients and those on antihypertensives; alpha-1 blockade causes orthostatic hypotension and fall risk.
  3. Administer with food to reduce sedation, improve absorption consistency, and minimize dizziness; the extended-release formulation should be taken on an empty stomach.
  4. At the low doses used for insomnia (25-100 mg), trazodone's H1 and alpha-1 antagonism predominate; counsel that this is an off-label use but widely practiced.

Clinical Pearls

  • Trazodone is one of the most commonly prescribed antidepressants in the United States — primarily for insomnia at doses far below its antidepressant range (25-100 mg vs. 150-600 mg), creating a dual role as sedative-hypnotic and antidepressant.
  • Its active metabolite mCPP is a serotonin agonist and can cause anxiety, headache, and dizziness if it accumulates, particularly when co-administered with CYP3A4 inhibitors.

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Major Depressive Disorder Off-label: Anxiety Off-label: Fibromyalgia Pain Off-label: Insomnia (most Common Use At Low Doses) Serotonin Antagonist And Reuptake Inhibitor (SARI)
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