What is the recommended dosage of doxepin (tricyclic antidepressant) for functional dyspepsia?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 1, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Doxepin Dosage for Functional Dyspepsia

Direct Answer

Doxepin is not recommended for functional dyspepsia; amitriptyline is the preferred tricyclic antidepressant, starting at 10 mg once daily in the evening and titrating slowly to 30-50 mg daily. 1

Preferred Tricyclic Antidepressant Selection

The British Society of Gastroenterology specifically recommends amitriptyline as the tricyclic antidepressant of choice for functional dyspepsia, not doxepin. 1 This represents a strong recommendation with moderate-quality evidence. 1

Amitriptyline Dosing Protocol

  • Starting dose: 10 mg once daily in the evening 1
  • Titration: Increase slowly by 10 mg weekly or every 2 weeks to improve tolerability 1
  • Target dose: 30-50 mg daily 1
  • Trial duration: 6-8 weeks with at least 2 weeks at maximum tolerated dose 2

Alternative Tricyclic Options

If amitriptyline is not tolerated, nortriptyline (a secondary amine) can be considered as it has a theoretically more favorable side effect profile, though clinical evidence is stronger for amitriptyline. 1 For nortriptyline, start at 25 mg at bedtime and increase by 25 mg every 3-7 days as tolerated, up to 150 mg/day. 2

However, a 2018 randomized controlled trial found nortriptyline 10 mg daily was not superior to placebo in Asian patients with functional dyspepsia (response rate 53.6% vs 57.6%, P=0.75). 3

Treatment Algorithm Position

Tricyclic antidepressants should be initiated after failure of: 1

  1. H. pylori testing and eradication (if positive) 2, 1
  2. Proton pump inhibitor trial (4-8 weeks) 1, 4
  3. Prokinetic agents (acotiamide 100 mg three times daily or itopride) 5, 6

Tricyclic antidepressants rank second in network meta-analyses for functional dyspepsia treatment efficacy. 1

Evidence for Amitriptyline Efficacy

A 2015 multicenter randomized controlled trial demonstrated that amitriptyline 50 mg provided adequate relief in 53% of patients versus 40% with placebo (P=0.05). 7 The benefit was particularly pronounced in ulcer-like (painful) functional dyspepsia, where patients were 3-fold more likely to report adequate relief (odds ratio 3.1,95% CI: 1.1-9.0). 7

Patient Education and Side Effect Management

Critical counseling point: Explain that tricyclic antidepressants function as gut-brain neuromodulators, not antidepressants, to improve patient acceptance and adherence. 1

Common Side Effects

  • Sedation 1
  • Dry mouth 1
  • Dry eyes 1
  • Constipation 1

Slow titration significantly improves tolerability and reduces discontinuation rates. 1

Important Caveats

  • Cardiac screening: Obtain baseline ECG in patients over 40 years before initiating therapy 2
  • Cardiac caution: Use with caution in ischemic heart disease or ventricular conduction abnormalities, limiting doses to <100 mg/day when possible 2
  • Delayed gastric emptying: Patients with documented delayed gastric emptying are less likely to respond to tricyclic antidepressants (odds ratio 0.4,95% CI: 0.2-0.8) 7
  • Refractory cases: Consider referral to multidisciplinary pain centers or gastroenterology specialists for severe or treatment-resistant functional dyspepsia 1

References

Guideline

Treatment of Functional Dyspepsia with Tricyclic Antidepressants

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Guidelines for the management of dyspepsia.

The American journal of gastroenterology, 2005

Guideline

Acotiamide Treatment for Functional Dyspepsia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Itopride Treatment Protocol for Functional Dyspepsia and GERD

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Related Questions

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.