Maximum Dose of Amitriptyline
The maximum dose of amitriptyline is 150 mg/day for outpatients and 300 mg/day for hospitalized patients, though most patients should not exceed 150 mg/day due to increased risk of adverse effects without proportional benefit. 1
Dosing by Clinical Context
For Depression (Outpatients)
- Starting dose: 75 mg/day in divided doses or 50-100 mg at bedtime 1
- Standard maximum: 150 mg/day 1
- Titration: Increase by 25-50 mg as necessary, preferably in late afternoon/bedtime doses 1
- Time to effect: Adequate therapeutic response may take up to 30 days 1
For Hospitalized Patients with Depression
- Starting dose: 100 mg/day 1
- Standard maximum: 200 mg/day 1
- Absolute maximum: 300 mg/day (only for a small number of hospitalized patients who require higher doses) 1
For Neuropathic Pain
- Starting dose: 25 mg at bedtime 2
- Titration: Increase by 25 mg/day every 3-7 days as tolerated 2
- Maximum dose: 150 mg/day 2
- Important caveat: If blood concentration of active medication and its metabolite is <100 ng/mL, continue titration with caution beyond 150 mg/day 2
- Duration of adequate trial: 6-8 weeks with at least 2 weeks at maximum tolerated dosage 2
For Cyclic Vomiting Syndrome (Prophylaxis)
- Starting dose: 25 mg at bedtime 2
- Goal dose: 75-150 mg or 1-1.5 mg/kg at bedtime 2
- Titration: Slow titration (10-25 mg increments every 2 weeks up to goal dosage) is generally better tolerated 2
Special Populations
Adolescent and Elderly Patients
- Recommended dosing: 10 mg three times daily with 20 mg at bedtime 1
- Maximum: Generally should not exceed 40-100 mg/day 2, 1
- Rationale: Lower doses recommended due to decreased tolerance and altered pharmacokinetics 1
- Monitoring: Plasma levels are generally higher for a given oral dose in elderly patients due to increased intestinal transit time and decreased hepatic metabolism 1
Alzheimer's Disease/Dementia Patients
- Initial dose: 10-25 mg in the morning 2
- Maximum dose: 150 mg in the morning 2
- Note: Secondary amine TCAs (nortriptyline, desipramine) are preferred over tertiary amines like amitriptyline in this population 2
Critical Safety Considerations
Cardiac Toxicity
- Prescribe with caution in patients with ischemic cardiac disease or ventricular conduction abnormalities 2
- Limit dosages to <100 mg/day when possible in at-risk patients 2
- Obtain screening ECG for patients older than 40 years before initiating therapy 2
- Monitor for prolonged QTc on ECG 2
Common Adverse Effects (Dose-Dependent)
- Somnolence, dry mouth, blurred vision, constipation, weight gain 2
- Incidence increases significantly at 75 mg vs lower doses 3
- At 75 mg dose, 64% of patients experience at least one adverse event vs 40% with placebo 4
Therapeutic Drug Monitoring
- Recommended therapeutic range: 80-200 ng/mL (amitriptyline plus nortriptyline) 2
- Plasma levels are difficult to directly correlate with therapeutic effect but useful for identifying toxic levels or noncompliance 1
- Elderly patients should be monitored carefully with quantitative serum levels obtained as clinically appropriate 1
Evidence Quality Considerations
The evidence supporting amitriptyline dosing comes primarily from FDA labeling and clinical guidelines, but efficacy data is limited. There is no top-tier evidence (high-quality RCTs with ≥200 participants) supporting amitriptyline for neuropathic pain or fibromyalgia 4. Second-tier evidence suggests only about 38% of participants benefit from amitriptyline vs 16% with placebo 4. Despite limited unbiased evidence, amitriptyline remains a first-line treatment based on decades of clinical experience 4.
Dose-response relationship exists for both efficacy and adverse effects: 75 mg provides significantly greater analgesic efficacy than 25 or 50 mg in chronic pain, but adverse effects also increase significantly at this dose 3. The analgesic effect is modest and unrelated to mood elevation 5, 3.