Amitriptyline inhibits the reuptake of serotonin (5-HT) and norepinephrine (NE) at presynaptic neurons, increasing their availability in the synaptic cleft. This enhances mood regulation and pain modulation. Additionally, it blocks:

1. Histamine H1 Receptors: Causes sedation.
2. Muscarinic Acetylcholine Receptors: Leads to anticholinergic effects (e.g., dry mouth, constipation).
3. Alpha-1 Adrenergic Receptors: Contributes to orthostatic hypotension (Lippincott Textbook of Pharmacology).

1. Major Depressive Disorder (MDD):
   • Effective for severe depression, though less commonly used due to side effects (BNF).
2. Neuropathic Pain:
   • First-line treatment for diabetic neuropathy, postherpetic neuralgia, and fibromyalgia (Lange Basic & Clinical Pharmacology).
3. Migraine Prophylaxis:
   • Reduces the frequency and severity of migraines.
4. Chronic Tension-Type Headache:
   • Used off-label for prevention.
5. Insomnia:
   • Low doses are sometimes used for sleep disturbances (Lippincott).

• Adults:
  • Depression: Start with 25–50 mg at bedtime, titrate to 75–150 mg/day in divided doses or as a single nighttime dose (BNF).
  • Neuropathic Pain/Migraine: Start with 10–25 mg at bedtime, titrate to 50–150 mg/day (Lange Basic & Clinical Pharmacology).
• Elderly:
  • Start with 10 mg at bedtime, titrate cautiously to avoid side effects (Lippincott).

Administration:

• Take at bedtime to minimize daytime sedation.
• Avoid abrupt discontinuation; taper gradually over weeks to prevent withdrawal symptoms (BNF).

• Common: Dry mouth, constipation, blurred vision, sedation, weight gain, and orthostatic hypotension (BNF).
• Serious:
  • Cardiac Arrhythmias: Due to QT prolongation, especially in overdose.
  • Seizures: Increased risk in predisposed individuals.
  • Hyponatremia: Especially in elderly patients (Lippincott).
  • Suicidal Ideation: Increased risk in adolescents and young adults (Lange Basic & Clinical Pharmacology).

• Contraindications:
  • Recent myocardial infarction, arrhythmias, or severe liver disease.
  • Concurrent use of MAO inhibitors (BNF).
• Monitoring:
  • ECG in patients with cardiac risk factors.
  • Serum sodium levels in elderly patients (Lippincott).
• Pregnancy/Lactation:
  • Category C: Use only if benefits outweigh risks; potential neonatal withdrawal.
  • Excreted in breast milk—consult a specialist (Lange Basic & Clinical Pharmacology).

• MAO Inhibitors: Risk of serotonin syndrome; allow a 14-day washout period (BNF).
• CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): Increase amitriptyline levels; monitor for toxicity.
• Anticholinergic Drugs (e.g., antihistamines, antipsychotics): Enhanced anticholinergic effects.
• QT-Prolonging Drugs (e.g., amiodarone, antipsychotics): Increased risk of arrhythmias (Lippincott).

Amitriptyline is the generic name. Brand names include Elavil® and Lentizol®. Generic formulations are widely available as:

• Tablets: 10 mg, 25 mg, 50 mg.
• Oral Solution: 10 mg/5 mL (BNF).