III. Precautions

  1. See Tricyclic Antidepressants
  2. See Tricyclic Antidepressant Overdose
  3. Serious cardiotoxicity in overdosage

IV. Mechanism

  1. See Tricyclic Antidepressant
  2. Amitriptyline primarily inhibits Serotonin reuptake
  3. Amitriptyline is demethylated to Nortriptyline, which primarily inhibits Norepinephrine reuptake

V. Pharmacokinetics

  1. Serum Half Life: 30 to 45 hours
  2. Therapeutic plasma level: 110 to 250

VI. Safety

  1. Pregnancy Category C
  2. Avoid in Lactation

VII. Dosing: Migraine Headache Prophylaxis, Fibromyalgia or Chronic Pain

  1. Start at 25 mg orally at bedtime for 3 days
  2. Next: 50 mg orally at bedtime for 3 days
  3. Therapeutic Target Dose: 75 mg orally at bedtime (range 50 to 100 mg/day)

VIII. Dosing: Insomnia

  1. Initial: 25 mg orally at bedtime
  2. Morning Hangover Effect: Taper to 10 mg orally at bedtime

IX. Dosing: Major Depression (listed for historical purposes only)

  1. Avoid for Major Depression given adverse effects
    1. SSRIs and other new Antidepressants are preferred
  2. Adults
    1. Start 50-100 mg orally at bedtime (or 25 mg orally three times daily)
    2. Titrate to 150 mg orally at bedtime (or in divided doses)
    3. Max Dose: 300 mg daily
  3. Elderly and Children over age 12 years
    1. Start 10 mg orally three times daily and 25 mg orally at bedtime
    2. Titrate dose as needed
    3. Max Dose: 200 mg daily

X. Adverse Effects

  1. See Tricyclic Antidepressants
  2. Tricyclic Antidepressant Overdose
  3. Amitriptyline is among the most Anticholinergic of the Tricyclic Antidepressants (including Sedative effects)
    1. Consider Nortriptyline as an alternative
  4. Significant adverse effects
    1. Sedation and morning grogginess
    2. Anticholinergic Symptoms
    3. Orthostatic Hypotension
    4. Cardiac Arrhythmia
    5. Weight gain

XI. Drug Interactions

XIII. References

  1. (2023) Med Lett Drugs Ther 62(1592): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 36-7
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia

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Related Studies

Cost: Medications

amitriptyline (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
AMITRIPTYLINE HCL 10 MG TAB Generic $0.04 each
AMITRIPTYLINE HCL 100 MG TAB Generic $0.15 each
AMITRIPTYLINE HCL 150 MG TAB Generic $0.17 each
AMITRIPTYLINE HCL 25 MG TAB Generic $0.05 each
AMITRIPTYLINE HCL 50 MG TAB Generic $0.09 each
AMITRIPTYLINE HCL 75 MG TAB Generic $0.13 each