Amitriptyline Dosing for Gastroparesis and Nausea
For gastroparesis-related nausea and visceral pain, start amitriptyline at 10 mg at bedtime and titrate up to 25-100 mg daily based on symptom response and tolerability. 1
Recommended Dosing Strategy
Initial dosing should begin at 10 mg three times daily with 20 mg at bedtime (total 50 mg/day) for outpatients, or alternatively 50-100 mg as a single bedtime dose. 2 However, for gastroparesis specifically, the American Gastroenterological Association recommends starting at the lower end of this range (25 mg/day) and titrating to 25-100 mg/day based on clinical response. 1
Titration Approach
- Start with 10-25 mg at bedtime to minimize side effects and assess tolerability 1, 2
- Increase by 10-25 mg every 1-2 weeks as needed for symptom control 2
- Target dose range is 25-100 mg daily for visceral pain and nausea management in gastroparesis 1
- Maximum outpatient dose is typically 150 mg/day, though gastroparesis rarely requires doses this high 2
Mechanism and Expected Benefits
Tricyclic antidepressants like amitriptyline reduce visceral pain perception through noradrenaline reuptake inhibition and may help with anxiety, but they are NOT prokinetic agents. 1 The therapeutic effect may take up to 30 days to develop, though sedative effects appear earlier. 2
Clinical Considerations
- Amitriptyline addresses the visceral hypersensitivity and pain components of gastroparesis, not the delayed gastric emptying itself 1
- This medication is particularly useful when abdominal pain is a prominent symptom alongside nausea 1
- The sedative effect at bedtime dosing can be beneficial for patients with sleep disturbance from symptoms 2
Important Caveats and Contraindications
A major limitation is that nortriptyline (a related tricyclic) failed to show benefit over placebo in a rigorous randomized trial of idiopathic gastroparesis, though this does not definitively rule out amitriptyline's utility. 3 The NORIG trial found no improvement in overall gastroparesis symptoms with nortriptyline 75 mg daily, and 29% of patients discontinued due to side effects. 3
Safety Monitoring
- Monitor for anticholinergic side effects including constipation, which could theoretically worsen gastroparesis symptoms 4
- Elderly patients require lower doses (10 mg three times daily with 20 mg at bedtime) due to decreased hepatic metabolism and higher plasma levels 2
- Plasma level monitoring may be useful if toxic effects are suspected or if there is lack of clinical response suggesting non-compliance 2
Alternative Positioning in Treatment Algorithm
Amitriptyline should be considered as an adjunctive agent for pain and nausea, not as a replacement for standard gastroparesis therapy. 5, 1 Patients should first receive:
- Dietary modification (small particle size, low-fat diet for minimum 4 weeks) 5
- Metoclopramide 10 mg three times daily before meals and at bedtime as first-line pharmacotherapy 5
- 5-HT3 antagonists (ondansetron 4-8 mg 2-3 times daily) as second-line antiemetics 6
Amitriptyline serves as an adjunct when visceral pain, anxiety, or refractory nausea persist despite standard therapy. 1 It should NOT be used as monotherapy for gastroparesis. 5, 1
Maintenance Therapy
Once symptom improvement is achieved, reduce to the lowest effective dose (typically 40-100 mg/day) and continue for at least 3 months to prevent relapse. 2 The total daily dose can be given as a single bedtime dose for convenience during maintenance. 2