BSN Tracker

amitriptyline

Brand: Elavil

⚠ BBW Beers Criteria TDM Required Prototype Drug
Drug Class: tricyclic antidepressant (TCA)
Drug Family: antidepressant
Subclass: tertiary amine TCA
Organ Systems: cns

Mechanism of Action

Inhibits reuptake of both norepinephrine and serotonin; additionally blocks muscarinic, H1, and alpha-1 receptors, which accounts for its side effect profile. Sodium channel blockade at high concentrations explains its antiarrhythmic and neurotoxic properties in overdose.

NET (norepinephrine transporter)SERT (serotonin transporter)muscarinic receptorsH1 histamine receptoralpha-1 adrenergic receptorsodium channels

Indications

  • major depressive disorder
  • neuropathic pain
  • migraine prophylaxis
  • off-label: insomnia
  • off-label: fibromyalgia
  • off-label: interstitial cystitis

Contraindications

  • concurrent MAOI use
  • acute recovery phase post-MI
  • QT prolongation
  • concurrent cisapride use
  • glaucoma (narrow-angle)

Adverse Effects

Common

  • dry mouth
  • constipation
  • urinary retention
  • blurred vision
  • sedation
  • weight gain
  • orthostatic hypotension
  • tachycardia

Serious

  • QT prolongation and torsades de pointes
  • cardiac conduction disturbances
  • seizures (especially in overdose)
  • delirium (especially in elderly)
  • suicidal ideation

Pharmacokinetics (ADME)

Absorption well absorbed orally; bioavailability ~30-60% due to extensive first-pass metabolism
Distribution highly lipophilic; protein binding ~95%; large Vd ~6-10 L/kg; crosses BBB readily
Metabolism extensively hepatic via CYP2D6 (demethylation) and CYP2C19; active metabolite nortriptyline
Excretion primarily renal as metabolites; dose adjustment in hepatic impairment
Half-life 10-50 hours
Onset antidepressant 2-4 weeks; analgesic effect within 1 week
Peak 2-12 hours
Duration 24+ hours
Protein Binding 95%
Vd 6-10 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
MAOIs hypertensive crisis and serotonin syndrome contraindicated
CYP2D6 inhibitors (fluoxetine, paroxetine) increase TCA levels 2-10 fold; toxicity risk major
anticholinergic drugs additive anticholinergic toxicity (delirium, ileus, urinary retention) major
QT-prolonging agents additive QT prolongation major

Nursing Considerations

  1. Obtain baseline ECG before initiating; contraindicated with QTc >450 ms or bundle branch block; monitor ECG if dose exceeds 100 mg/day or patient has cardiac risk factors.
  2. Anticholinergic effects are pronounced in elderly patients — assess for urinary retention (void before administration), constipation, confusion, and dry mouth; amitriptyline is on the Beers Criteria list for patients >65.
  3. TCA overdose is a medical emergency: as few as 10-20x therapeutic dose can cause fatal arrhythmias; assess suicide risk and provide only limited supply (1-2 weeks) in high-risk patients.
  4. Orthostatic hypotension is common — have patient sit on edge of bed for 2 minutes before standing; particularly dangerous in elderly patients with fall risk.

Clinical Pearls

  • Amitriptyline's active metabolite nortriptyline is also used therapeutically and has a more favorable tolerability profile with similar efficacy, making it preferred in elderly patients requiring a TCA.
  • At low doses (10-75 mg), amitriptyline is highly effective for neuropathic pain, migraine prophylaxis, and insomnia — these analgesic and hypnotic effects occur below the antidepressant dose range.

Safety Profile

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

Concordance Terms

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

Major Depressive Disorder Migraine Prophylaxis Neuropathic Pain Off-label: Fibromyalgia Off-label: Insomnia Off-label: Interstitial Cystitis Tricyclic Antidepressant (TCA)
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