Amitriptyline

Amitriptyline is a tricyclic antidepressant (TCA) with a well-established profile for managing major depressive disorder and a range of chronic pain conditions. Its dual-action mechanism modulates serotonin and norepinephrine reuptake, offering both mood stabilization and central pain modulation. It is particularly valued in clinical practice for its efficacy in neuropathic pain, migraine prophylaxis, and as a second-line option for depression when SSRIs are ineffective or poorly tolerated. This product card provides a comprehensive, evidence-based overview for healthcare professionals.

Features

• Pharmacologic Class: Tricyclic Antidepressant (TCA)
• Mechanism of Action: Potent serotonin and norepinephrine reuptake inhibition; also exhibits anticholinergic, antihistaminic, and alpha-1 adrenergic blocking properties
• Bioavailability: Approximately 30–60% following oral administration, with significant first-pass metabolism
• Half-life: 10–28 hours, permitting once-daily dosing, typically at bedtime
• Protein Binding: >90%
• Metabolism: Hepatic, primarily via CYP2D6 and CYP2C19; active metabolite (nortriptyline)
• Excretion: Primarily renal

Benefits

• Provides robust relief from neuropathic pain, including diabetic neuropathy and postherpetic neuralgia
• Effective prophylactic treatment for chronic migraine and tension-type headaches
• Demonstrates efficacy in major depressive disorder, especially in cases with comorbid anxiety or insomnia
• Off-label utility in managing fibromyalgia, interstitial cystitis, and irritable bowel syndrome
• Cost-effective generic alternative with extensive clinical history and predictable pharmacokinetics
• Sedating properties beneficial for patients with sleep architecture disturbances

Common use

Amitriptyline is FDA-approved for the treatment of major depressive disorder. It is widely used off-label for chronic pain management, including neuropathic pain conditions such as diabetic neuropathy and postherpetic neuralgia. It is also employed prophylactically for migraine and tension-type headaches. Additional off-label uses include management of fibromyalgia, functional gastrointestinal disorders, and certain anxiety disorders. It is often selected when first-line treatments (e.g., SSRIs, SNRIs) are ineffective or contraindicated.

Dosage and direction

Initiate at low doses (e.g., 10–25 mg orally once daily at bedtime) to minimize anticholinergic and sedative effects. For depression, therapeutic doses typically range from 50–150 mg/day. For chronic pain or migraine prophylaxis, lower doses (10–75 mg/day) are often effective. Titrate gradually in increments of 10–25 mg every 5–7 days as tolerated. Maximum dose should not exceed 300 mg/day in divided doses for inpatients or 150 mg/day for outpatients. Use caution in elderly patients; initiate at 10 mg/day. Administer with food to reduce gastrointestinal upset.

Precautions

Monitor for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania. Screen patients for bipolar disorder prior to initiation. Use with caution in patients with a history of seizures, cardiovascular disease, glaucoma, urinary retention, or hyperthyroidism. May impair mental or physical abilities required for hazardous tasks. Orthostatic hypotension may occur. Periodic liver function tests and complete blood counts recommended during prolonged therapy. Abrupt discontinuation may lead to withdrawal symptoms; taper gradually.

Contraindications

Hypersensitivity to amitriptyline or other TCAs. Do not use within 14 days of MAOIs due to risk of serotonin syndrome. Contraindicated in patients with recent myocardial infarction, uncompensated heart failure, or conduction abnormalities. Avoid in patients with narrow-angle glaucoma or severe urinary retention. Not recommended during acute recovery phase after myocardial infarction.

Possible side effect

• Common: Dry mouth, blurred vision, constipation, urinary retention, drowsiness, dizziness, weight gain, orthostatic hypotension
• Serious: Suicidal ideation (particularly in young adults), seizures, cardiac arrhythmias, neuroleptic malignant syndrome, serotonin syndrome, agranulocytosis, jaundice, paralytic ileus
• Other: Increased appetite, sweating, confusion (especially in elderly), tinnitus, photosensitivity

Drug interaction

• MAOIs: Risk of serotonin syndrome, hypertensive crisis; contraindicated
• SSRIs/SNRIs: Increased risk of serotonin syndrome
• CNS depressants (e.g., alcohol, benzodiazepines, opioids): Additive sedation and respiratory depression
• Anticholinergics: Enhanced anticholinergic effects
• Antihypertensives: Potentiated hypotension
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): Increased amitriptyline levels
• Sympathomimetics: Enhanced pressor effects
• Warfarin: Increased anticoagulant effect

Missed dose

If a dose is missed, take it as soon as remembered unless it is close to the time for the next dose. Do not double the dose to make up for a missed one. Maintain regular dosing schedule to avoid fluctuations in plasma concentration.

Overdose

Symptoms include severe drowsiness, agitation, confusion, hallucinations, tachycardia, hypotension, cardiac arrhythmias, convulsions, coma, and respiratory depression. ECG monitoring is essential. Treatment is supportive and symptomatic; activated charcoal may be beneficial if administered early. Physostigmine is sometimes used for central anticholinergic effects but is not routinely recommended due to risk of seizures and bradycardia.

Storage

Store at room temperature (15–30°C or 59–86°F) in a tight, light-resistant container. Keep out of reach of children and pets. Do not use after expiration date.

Disclaimer

This information is intended for healthcare professionals and is not a substitute for clinical judgment. Prescribers should review full prescribing information and consider individual patient factors, including comorbidities, concomitant medications, and risk factors. Always verify dosing and contraindications prior to initiation.

Reviews

“Amitriptyline remains a cornerstone in my practice for managing refractory neuropathic pain. Its dual benefit on mood and pain pathways is invaluable, though anticholinergic side effects require careful titration.” – Neurologist, 15 years experience
“While newer agents are available, amitriptyline’s cost-effectiveness and efficacy in low doses for migraine prophylaxis make it a first-line choice for many of my patients.” – Headache Specialist
“Monitoring and patient education are key. The sedative properties can be beneficial, but caution is advised in the elderly due to fall risk.” – Geriatric Psychiatrist