What is the recommended dose of Amitriptyline (tricyclic antidepressant)?

Amitriptyline Dosing Recommendations

Start amitriptyline at 10-25 mg at bedtime and titrate gradually to a target dose of 25-75 mg daily for most chronic pain conditions, with a maximum of 150 mg daily for neuropathic pain and 300 mg daily for depression in outpatients. 1

Initial Dosing

• Begin with 10-25 mg at bedtime to minimize anticholinergic side effects and improve tolerability 2, 3
• For elderly patients, start at approximately 50% of the standard adult dose (10 mg at bedtime) due to significantly greater risk of adverse drug reactions 3, 1
• The FDA label specifies that for outpatients with depression, 75 mg daily in divided doses is usually satisfactory as a starting point, though lower initiation is common in clinical practice 1

Target Therapeutic Doses by Indication

Neuropathic Pain (Diabetic Peripheral Neuropathy)

• Target dose: 25-75 mg daily 2
• Goal dosage range: 75-150 mg or 1-1.5 mg/kg at bedtime for optimal pain control 3
• Maximum recommended: 150 mg daily 4
• Evidence shows doses >100 mg/day are associated with increased risk of sudden cardiac death, particularly in patients with cardiovascular disease 2

Irritable Bowel Syndrome

• Start at 10 mg at bedtime 2
• Titrate slowly to maximum of 30-50 mg at bedtime 4
• One study demonstrated efficacy of amitriptyline 10 mg at bedtime in IBS-D 2
• Most clinical trials used doses >50 mg daily, but lower doses are commonly effective in practice 2

Depression (Outpatient)

• Initial: 75 mg daily in divided doses 1
• May increase to 150 mg daily if necessary 1
• Maximum: 300 mg daily for outpatients 3, 1
• Hospitalized patients may require 100-200 mg daily initially, with some needing up to 300 mg daily 1

Headache/Migraine Prophylaxis

• Most patients respond to 10-25 mg daily 5
• Real-world evidence shows 63% of patients started on 10 mg daily with good efficacy 5
• In children: 1 mg/kg per day has demonstrated effectiveness 6

Titration Strategy

• Increase by 10-25 mg every 1-2 weeks based on tolerability and response 3, 4
• Make increases preferably in late afternoon and/or bedtime doses 1
• Slow titration significantly improves tolerability and medication persistence 4, 5
• Therapeutic effect may take up to 30 days to develop, though sedative effects appear earlier 3, 1

Maintenance Dosing

• Usual maintenance: 50-100 mg daily 1
• Some patients adequately controlled on 40 mg daily 1
• Total daily dose may be given as a single bedtime dose for convenience 1
• Continue maintenance therapy for at least 3 months to reduce relapse risk 1

Critical Safety Considerations

Cardiovascular Precautions

• Obtain ECG before initiating in patients with cardiac history 2
• Do not use if PR or QTc interval is prolonged 2
• Contraindicated in ischemic heart disease, stroke, peripheral vascular disease, uncontrolled hypertension, and decompensated heart failure 4
• Doses >100 mg/day associated with increased sudden cardiac death risk 2

Common Adverse Effects

• Anticholinergic effects: dry mouth, constipation, blurred vision, urinary retention 2, 3, 4
• Sedation and daytime fatigue (most common, 11% in headache patients) 3, 4, 5
• Orthostatic hypotension 3, 4
• Weight gain 3, 4
• QTc prolongation 4

Special Populations

• Elderly patients: Use 10 mg three times daily with 20 mg at bedtime as starting dose 1
• Adolescents: Same dosing as elderly; not recommended under age 12 1
• Beers Criteria: Amitriptyline is potentially inappropriate in older adults due to significant anticholinergic effects 3
• No dose adjustment needed for renal or hepatic disease 3

Therapeutic Drug Monitoring

• Recommended therapeutic range for amitriptyline plus nortriptyline: 80-200 ng/mL 3, 4
• Plasma levels useful for identifying toxic levels or suspected non-compliance 1
• Elderly patients generally have higher plasma levels for given oral doses due to decreased hepatic metabolism 1
• Adjust dosing based on clinical response, not solely on plasma levels 1

Clinical Pearls

• Lower doses (10-50 mg) are commonly effective in clinical practice despite most trials using >50 mg daily 2, 5
• Amitriptyline has balanced inhibition of noradrenaline and serotonin reuptake, potentially offering efficacy advantages over secondary amine TCAs (nortriptyline, desipramine), though secondary amines are better tolerated 2
• For IBS-C, consider secondary amine TCAs due to lower anticholinergic effects 2
• Number needed to treat (NNT) for neuropathic pain: 1.5-3.5 when carefully titrated 2
• Approximately 84% of headache patients report improvement, with 85% continuing medication at follow-up 5
• Most patients (73%) in pain clinics are treated with low doses (≤50 mg amitriptyline equivalent) 7