Elavil
Elavil
Generic Name
Elavil
Mechanism
Elavil (amitriptyline) is a first‑generation tricyclic antidepressant (TCA).
• Neurotransmitter inhibition – blocks presynaptic reuptake of norepinephrine (NE) and serotonin (5‑HT), increasing their synaptic concentrations.
• Receptor antagonism – competitively inhibits postsynaptic α‑adrenergic and muscarinic acetylcholine receptors, contributing to its antihistaminic, anticholinergic, and anti‑adrenergic side‑effect profile.
• Ion channel blockade – inhibits cardiac fast‑Na⁺ and slow‑K⁺ channels, prolonging the QT interval and reducing action‑potential conduction.
These combined actions underlie its antidepressant, analgesic, and chronotropic properties.
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Pharmacokinetics
- Absorption: Oral bioavailability ~50 % (first‑pass hepatic metabolism). Peak plasma levels in 2–6 h.
- Distribution: Large tissue volume (Vd ≈ 4–5 L/kg); highly lipophilic; crosses the blood–brain barrier efficiently.
- Metabolism: Primarily via CYP2C19 and CYP2D6 to active metabolites (nor‑ and didemethyl‑amitriptyline).
- Elimination: 80 % excreted in urine (≈ 60 % as metabolites).
- Half‑life: Parent drug 20–30 h; steady‑state reached 5–7 days; active metabolites 1–2 days.
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Indications
- Major depressive disorder (MDD) – standard or adjunctive therapy.
- Chronic neuropathic pain – diabetic neuropathy, post‑herpetic neuralgia; low‑dose 10–25 mg daily.
- Migraine prophylaxis – 25–50 mg nightly.
- Somnolence/insomnia – low‑dose (≤ 25 mg) at bedtime.
- Off‑label: fibromyalgia, chronic tension headaches, urinary urge incontinence, and some anxiety disorders.
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Contraindications
- Absolute contraindications:
- *Known hypersensitivity* to amitriptyline or other TCAs.
- Serious cardiac conduction abnormalities: bundle‑branch block, QRS >0.12 s, QTc >450 ms (male) / >460 ms (female).
- Severe hepatic or renal impairment (dose adjustments required).
- Warnings:
- Cardiac toxicity – arrhythmia, orthostatic hypotension.
- Seizure risk – lower seizure threshold, especially in bipolar or psychotic disorders.
- Suicidality – monitor for emergent suicidal ideation, especially in children, adolescents, and first 3 months of therapy.
- Pseudoporphyria – photosensitivity in elderly.
- Drug interactions: CYP2D6 inhibitors (fluoxetine, quinidine), MAO‑I, antipsychotics, antihistamines.
- Pregnancy/Breastfeeding: category C; use only if benefits outweigh risks.
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Dosing
| Indication | Starting Dose | Titration | Max Daily Dose | Administration |
| Depression | 25–50 mg nightly (or divided) | Increase 25–50 mg q(2–4) weeks | 150–200 mg | Oral capsules/tablets |
| Neuropathic pain | 10–25 mg nightly | Increase 10 mg every 1–2 weeks | 100–150 mg | Oral |
| Migraine prophylaxis | 10–25 mg nightly | Titrate 10 mg q(1–2 weeks) | 100 mg | Oral |
| Insomnia | ≤ 25 mg at bedtime | Titrate within 1 week | 25 mg | Oral |
• Special populations:
• *Elderly*: start low (10–25 mg) to avoid anticholinergic toxicity.
• *Renal/hepatic impairment*: reduce dose by 30–50 %.
• Missed dose: take when remembered; skip if close to next dose.
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Adverse Effects
Common (≥10 %)
• Dry mouth, blurred vision, constipation, urinary retention.
• Drowsiness, dizziness, weight gain, orthostatic hypotension.
• Sexual dysfunction (decreased libido, delayed orgasm).
Serious (≤1 %)
• Cardiac: arrhythmias (VT/VF), QT prolongation → monitor ECG.
• Seizures: Lower threshold → avoid in seizure disorders.
• Anticholinergic toxicity: delirium, confusion, hyperthermia.
• Overdose: GI upset, arrhythmias, CNS depression – rapid de‑contamination (activated charcoal).
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Monitoring
| Parameter | Frequency | Rationale |
| ECG | Baseline, at dose ≥ 75 mg/day or new cardiac symptoms | QTc & QRS monitoring |
| Weight, BP, pulse | Every 4–6 weeks | Anticholinergic & antihypertensive effects |
| Serotonin syndrome | Clinical review | When combined with MAO‑I or SSRIs |
| Serum amitriptyline level | After 5–7 days, at dosage change | Avoid toxic concentrations (> 200 ng/mL) |
| Kidney/liver panels | Every 3–6 months | Adjust dose in impairment |
| Pregnancy monitoring | Obstetric visits | Fetal risk assessment |
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Clinical Pearls
- Low‑Dose Strategy: For pain or insomnia, start ≤ 25 mg nightly; many patients experience benefits with minimal sedation.
- Drug–Drug Alerts: Amitriptyline + *quinidine* or *cisapride* → marked QT prolongation; avoid combination.
- Polypharmacy Caution: Co‑prescribed with SSRIs or SNRIs increases serotonin syndrome risk.
- Overdose Management: Instruct patients to keep medication bottles secure; consider a dedicated “danger” box for high‑risk individuals.
- Anticholinergic Burden: In the elderly, consider total anticholinergic scale (e.g., Anticholinergic Cognitive Burden) when adding Elavil.
- Patient Education: Emphasize that sleep improvement takes 2–4 weeks; advise use of sleep hygiene adjuncts.
- Use in Diabetic Neuropathy: Low dose (10–25 mg) is often *induction of choice* before moving to newer agents.
- Heart‑Failure Patients: Avoid high doses; monitor for fluid retention and arrhythmia.
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