Overview
Amitriptyline is a tricyclic antidepressant (TCA) primarily used to treat major depressive disorder, neuropathic pain, migraine prophylaxis, and other conditions. It works by increasing levels of serotonin and norepinephrine in the brain.
Mechanism of Action
Amitriptyline inhibits the reuptake of serotonin and norepinephrine at presynaptic neuronal membranes, increasing their concentration in the synaptic cleft. It also exhibits anticholinergic, antihistaminic, and alpha-adrenergic blocking properties.
Indications
- Major depressive disorder
- Neuropathic pain (e.g., diabetic neuropathy, postherpetic neuralgia)
- Migraine prophylaxis
- Tension-type headache prophylaxis
- Fibromyalgia (off-label)
- Nocturnal enuresis in children (off-label)
- Anxiety disorders (off-label)
Dosage
For depression: Initial dose 25-75 mg daily, may increase gradually to 150-300 mg daily. For neuropathic pain/migraine: Lower doses (10-100 mg daily) often used. Administer as a single dose at bedtime to minimize daytime sedation. Adjust based on response and tolerability.
Contraindications
- Hypersensitivity to amitriptyline or other TCAs
- Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation
- Recent myocardial infarction
- Heart failure
- Severe liver disease
- Narrow-angle glaucoma
- Urinary retention
Side Effects
- Sedation/drowsiness
- Dry mouth
- Blurred vision
- Constipation
- Urinary retention
- Weight gain
- Orthostatic hypotension
- Tachycardia
- Confusion (especially in elderly)
- Sexual dysfunction
- Increased appetite
- Sweating
Interactions
- MAOIs: Risk of serotonin syndrome, hypertensive crisis
- SSRIs/SNRIs: Increased risk of serotonin syndrome
- Anticholinergics: Enhanced anticholinergic effects
- Antihypertensives: May reduce blood pressure control
- CNS depressants (alcohol, benzodiazepines): Enhanced sedation
- Sympathomimetics: Increased cardiovascular effects
- Warfarin: May increase anticoagulant effect