What is the recommended starting dose, titration schedule, maximum dose, and special considerations for amitriptyline in adults, including the elderly or patients with cardiac conduction disease?

Amitriptyline Dosing for Adults

For most adult outpatients, start amitriptyline at 10-25 mg at bedtime and titrate slowly by 10-25 mg increments every 1-2 weeks to a target dose of 50-150 mg daily, with doses above 100 mg/day requiring caution due to increased cardiac risk. 1, 2

Starting Dose

• Outpatients: Begin with 10-25 mg at bedtime 2, 1
• Hospitalized patients: May start at 100 mg daily, gradually increasing to 200 mg if necessary 1
• Elderly patients: Start at 10 mg three times daily with 20 mg at bedtime (total 50 mg/day) 1, 2
• Adolescents: Use the same conservative dosing as elderly patients (10 mg three times daily with 20 mg at bedtime) 1

Titration Schedule

• Increase by 10-25 mg increments every 1-2 weeks based on tolerability and response 2
• Make dose increases preferably in the late afternoon and/or bedtime doses 1
• Slower titration is better tolerated and may improve medication persistence 2, 3
• Allow 2 weeks at the highest tolerated dose before determining treatment failure 2

Target and Maximum Doses

Standard Dosing

• Target therapeutic range: 50-150 mg daily for most indications 1, 2
• Maintenance dose: 50-100 mg daily (some patients respond to 40 mg daily) 1
• Maximum outpatient dose: 150 mg daily 1
• Maximum hospitalized patient dose: 200-300 mg daily (small number may require 300 mg) 1

Indication-Specific Dosing

• Painful diabetic neuropathy: 25-75 mg/day 2
• Neuropathic pain (cancer-related): Start 10-25 mg nightly, increase to 50-150 mg nightly 2
• Cyclic vomiting syndrome prophylaxis: Start 25 mg at bedtime, goal 75-150 mg or 1-1.5 mg/kg at bedtime 2

Critical Safety Thresholds

Doses above 100 mg/day are associated with increased risk of sudden cardiac death and should be avoided in patients with cardiovascular disease. 2

Cardiac Monitoring Requirements

• Obtain baseline ECG in patients over 40 years of age before initiating therapy 2
• Do not use if PR interval or QTc is prolonged on baseline ECG 2
• Limit doses to <100 mg/day when possible to reduce cardiac risk 2
• Monitor for heart rate increases (mean increase of 16 beats per minute expected) 4

Special Population Considerations

Elderly Patients (≥75 years)

• Start at 10 mg three times daily with 20 mg at bedtime 1
• Plasma levels are generally higher for a given dose due to decreased hepatic metabolism and increased intestinal transit time 1
• Monitor carefully with quantitative serum levels as clinically appropriate 1
• Higher risk of anticholinergic effects including sedation, dry mouth, urinary hesitancy, and falls 2

Patients with Cardiac Disease

• Use with extreme caution in those with ischemic cardiac disease or ventricular conduction abnormalities 2
• Obtain screening ECG and avoid use if conduction abnormalities present 2
• Keep doses below 100 mg/day 2
• Consider alternative agents (nortriptyline, desipramine) which have less cardiac toxicity 2

Common Pitfalls and How to Avoid Them

Anticholinergic Side Effects

• Most common: Dry mouth, drowsiness, somnolence, sedation, fatigue, constipation, blurred vision 2, 5
• These effects are predictable and frequent but can be minimized by slow titration 2
• Anticholinergic effects occur regardless of dose and are not dose-dependent 5
• Secondary amines (nortriptyline, desipramine) have fewer anticholinergic properties if tolerability is an issue 2

Timing of Therapeutic Effect

• Sedative effects may appear before antidepressant or analgesic effects 1
• Adequate therapeutic effect may take 30 days to develop for depression 1
• Analgesic onset is usually earlier than antidepressant effect 2
• Do not prematurely discontinue therapy; allow adequate trial duration 2

Dosing Administration

• Administer entire daily dose at bedtime for maintenance therapy to improve adherence and minimize daytime sedation 1, 2
• Once-daily dosing at bedtime is preferred over divided doses 2, 1

Maintenance Therapy

• Continue maintenance therapy for 3 months or longer to lessen possibility of relapse 1
• Once satisfactory improvement is reached, reduce to the lowest dose that maintains symptom relief 1
• Many patients in clinical practice respond to lower doses (10-25 mg) than used in clinical trials 3
• 85% of headache patients remain on therapy at follow-up when using low-dose regimens 3