amitriptyline ELAVIL

Class: TCA/​3° Amine Dibenzocycloheptadiene
FDA Indications: MDD, Nocturnal Enuresis In Children
Off-Label Use: Neuropathic Pain, Postherpetic Neuralgia, Migraines, Insomnia, Eating Disorders, Fibromyalgia
Prescribing
Forms: 10, 25, 50, 75, 100, 125, 150mg tablet; 10 mg/mL injectable
Dose Range: 50-300 mg/day
Starting: 25 mg qd qhs, ↑ by 25 mg q3-7 days, increase to 150 mg. May be taken in divided doses.
Stopping: ↓ 50% x3 days, then ↓ another 50% x3 days, then D/C entirely.
Monitoring: Suggested plasma level 250-825 nmol/L (recommended for MDD)

NAMI drug fact sheet

Precautions
Contraindications: Concomitant use of MAOIs; patient s/p MI; coadministration of other QT-prolonging agents; h/o QT ↑ or arrhythmia; caution in patients with hypo-K+ or hypo-Mg2+
Serious Side Effects: 5HT syndrome; ↓ seizure threshold; ↑ arrhythmias, tachycardia, orthostatic hypotension
Side Effects: anticholinergic side effects, weight gain, sexual dysfunction
Pharmacodynamics
1° MOA: Tricyclic antidepressant
Target: SERT, NET, H1, α1, M1, 5HT2A
Pharmacokinetics
t½: 21 (10-46)° TMAX: 2-12°
Substrate of: 2C19, 3A4; 2D6
Inhibits: 2D6, 2C19; Induces: ∅
Active Metabolites: nortriptyline (t½ 18-44°)
DDIs
  • - DO NOT CO-PRESCRIBE WITH MAOIs (need a 14-day washout period)
  • - caution combining with other CNS depressants & anticholinergics
  • - CBZ can ↓ levels by ~50% via 3A4 induction
  • - VPA may ↑ levels
Misc
  • - popular TCA in treatment of headaches and numerous chronic pain syndromes
  • - commonly used for insomnia
  • - addition of T3 may potentiate effects
  • - most anticholinergic TCA
Special Populations

Category C—A case-control study showed ∅ ↑ congenital malformations with 1st trimester use & a review (n=209) showed ∅ assoc with congenital malformations or developmental delay.

RID 1.9-2.8%


Avoid due to its anticholinergicity and high sedation, especially when combining with other CNS depressants and/or anticholingerics. Caution regarding orthostatic hypotension (fall risk!). Can impair cognition.


2019 BEE℞S Recommendation: Avoid. Highly anticholinergic, sedating, and cause orthostatic hypotension.

No dosage adjustment necessary.


All TCAs are hepatically metabolzed, highly protein bound and will accumulate, and associated with ↑ LFTs. Especially sedating TCAs (e.g. amitriptyline) should be avoided.

References
Applied Clinical Pharmacokinetics And Pharmacodynamics Of Psychopharmacological Agents
Concise Guide To Drug Interaction Principles For Medical Practice
Foye's Principles Of Medicinal Chemistry
Pharmacology For Women's Health
Drug Interactions In Psychiatry, 3rd Ed.
Antidepressant Use During Pregnancy

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Last updated August 16 2023 14:43:53. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.