What is the maximum recommended dose of Amitriptyline (tricyclic antidepressant) per day for adults?

Maximum Dose of Amitriptyline

The maximum recommended dose of amitriptyline is 300 mg per day for hospitalized patients, while outpatients should not exceed 150 mg per day according to FDA labeling and clinical practice guidelines. 1, 2

FDA-Approved Maximum Dosing

• For outpatients: The FDA label specifies a maximum of 150 mg per day, with initial dosing of 75 mg daily in divided doses or 50-100 mg at bedtime 1
• For hospitalized patients: Up to 300 mg per day may be used in a small number of cases who require higher doses 1
• The American Academy of Family Physicians aligns with FDA guidance, recommending a maximum of 300 mg per day for outpatient treatment, though this appears to reference the absolute maximum rather than typical outpatient practice 2

Practical Dosing by Indication

Neuropathic Pain

• Target dose is 75-150 mg at bedtime, with most patients responding to doses well below the maximum 2
• Doses above 100 mg/day are associated with increased risk of sudden cardiac death, particularly in patients with cardiovascular disease 2
• Clinical trial data demonstrates efficacy at a maximum of 150 mg nightly for diabetic neuropathy, with patients tolerating higher doses reporting greater pain relief 3

Depression

• Initial dosing starts at 50-100 mg at bedtime for outpatients, increased by 25-50 mg increments to 150 mg per day 1
• Hospitalized patients may start at 100 mg daily, gradually increased to 200 mg daily if necessary 1

Headache/Migraine Prevention

• Real-world data shows most patients achieve benefit at 10-25 mg daily (58% of patients), with maximum doses ranging only to 100 mg daily 4
• Traditional clinical trial doses of 30-150 mg/day are recommended by guidelines, but lower doses (10-50 mg) are commonly effective in practice 2, 4

Critical Safety Considerations

Cardiac Monitoring

• Obtain an ECG before initiating amitriptyline in patients with cardiac history; do not use if PR or QTc interval is prolonged 2
• The risk of sudden cardiac death increases significantly above 100 mg/day, especially in cardiovascular disease 2

Special Populations

• Elderly patients should receive approximately 50% of the adult starting dose (10 mg three times daily with 20 mg at bedtime) due to significantly greater risk of adverse drug reactions 1, 2
• Elderly patients have higher plasma levels for a given oral dose due to increased intestinal transit time and decreased hepatic metabolism 1
• Adolescent patients should also use lower dosages, similar to elderly patients 1

Titration Strategy

• Start at 10-25 mg at bedtime to minimize anticholinergic side effects 2, 1
• Increase gradually every 3-7 days by 10-25 mg increments as tolerated 2
• Increases should preferably be made in late afternoon and/or bedtime doses 1
• A minimum of 6-8 weeks with at least 2 weeks at maximum tolerated dose is required to assess efficacy 2

Therapeutic Drug Monitoring

• Therapeutic range for amitriptyline plus its active metabolite nortriptyline is 80-200 ng/mL (some sources cite 100-250 ng/mL for amitriptyline alone) 2
• At 150 mg/day, expect combined amitriptyline levels of 100±41 ng/mL plus nortriptyline levels of 71±38 ng/mL 5
• Plasma level monitoring is useful when approaching maximum doses, in elderly patients, or when toxic effects or noncompliance is suspected 1, 2

Common Pitfalls

• Nearly half (46.7%) of patients prescribed amitriptyline have at least one precaution or contraindication for its use, yet it continues to be prescribed 6
• The drug is potentially inappropriate in older adults per Beers Criteria due to significant anticholinergic effects 2
• Contraindications include recent myocardial infarction, arrhythmias, heart block, and prolonged QTc syndrome 2, 7
• Most adverse effects (sedation, dry mouth, orthostatic hypotension, confusion, weight gain, urinary retention, constipation, blurred vision) are dose-dependent 2