What is Amitriptyline?

  • Belongs in a class of medication called tricyclic antidepressants

  • FDA Approved Medication for treating major depressive disorder (MDD) in adults

  • Blocks the norepinephrine and

       serotonin transporters (NET or SERT) at

       presynaptic terminals

       = increase noradrenergic or

       serotonergic neurotransmission

  • Also blocks postsynaptic histamine,

       acetylcholine, and alpha-adrenergic

       receptors = side effects

  • Tablets: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

  • Dosage range: 10 mg – 150 mg (depending on the condition to be


  • For depression: starting dose is usually 25 mg

  • For chronic pain: starting dose is usually lower, 10 mg

  • Doses are lower in adolescents, geriatric patients

  • Increased by 25 mg every 3-7 days

  • Maximum 150-300 mg/day

  • Onset of action: approximately 2-4 weeks​

  • Metabolized by: liver (enzymes CYP3A4, CYP2C19)

  • Pregnancy: Category C

  • No well-controlled studies but with reports of limb deformities,

       developmental delay, and central nervous system effects on babies

  • Breastfeeding: use with caution

  • Rarely, causes sedation in baby

Off-label use:

  • Pain: chronic pain, neuropathic pain, postherpetic neuralgia

                                                                     Start dose around 10 mg

  • Exert acute anti-allodynic action through central alpha-2A adrenoceptor-

             dependent mechanism and chronic pain relief through a peripheral and
             Beta2-adrenoceptors dependent mechanism that relies on an anti-
             neuroimmune action of the drug

  • Noradrenaline reuptake inhibition enhances analgesic effects, mainly through

             α2-adrenergic receptors in the dorsal horn of the spinal cord

  • Migraine prophylaxis                                 10-25 mg PO; range 10-400 mg

                                                                             trials: 25-50 mg PO

Off-label use:

  • Insomnia

  • Anxiety

  • Post-traumatic stress disorder

  • Sialorrhea (Excessive salivation such as in ALS)

  • Irritable bowel syndrome, functional dyspepsia, chronic pelvic pain

  • Fibromyalgia

Common Side-Effects:

  • Xerostomia (dry mouth)

  • Drowsiness, sedation

  • Blurred vision

  • Confusion

  • Cognitive impairment

  • Dizziness

  • Headache

  • Weight gain

  • Gastrointestinal symptoms (eg. Constipation)

  • Urinary retention

  • Hypotension, orthostasis

Contraindications or Cautions

  • Cardiac conduction abnormalities: right bundle branch block,

  • arrhythmia, prolonged QTc interval

  • Do not give in patients on MAO inhibitors (like selegiline in Parkinsons

       patients) due to risk for hypertensive crisis

  • Suicidal and impulsive patients: may be lethal in overdose

  • Epilepsy: lower seizure threshold

  • Elderly: hypotension, falls

  • Worsens: narrow-angle glaucoma, urinary retention, imbalance,

       cognitive impairment or dementia