What is the recommended starting dose and titration schedule of amitriptyline for an adult with globus sensation presumed secondary to anxiety or depression?

Amitriptyline Dosing for Globus Sensation

For globus sensation in adults, start amitriptyline at 10 mg at bedtime and titrate by 10 mg every 1–2 weeks based on response and tolerability, targeting a maximum dose of 25–30 mg daily, as higher doses (>100 mg/day) increase cardiovascular risk without additional benefit for this indication. 1, 2, 3

Starting Dose and Rationale

• Begin with 10 mg at bedtime to minimize anticholinergic side effects (dry mouth, constipation, sedation) and improve tolerability, consistent with American Gastroenterological Association recommendations for functional esophageal disorders. 1, 2

• The low starting dose is particularly important because globus sensation is a functional disorder where visceral hypersensitivity—not severe pain—is the primary mechanism, and lower doses are typically effective. 1, 2

• A randomized controlled trial specifically in globus pharyngeus demonstrated that 25 mg amitriptyline at bedtime for 4 weeks achieved a 75% response rate (defined as >50% symptom reduction), significantly superior to proton pump inhibitor therapy (35.7% response, P=0.004). 3

Titration Schedule

• Increase by 10 mg every 1–2 weeks as tolerated, allowing 2–3 weeks at each dose level to assess efficacy before further escalation. 1, 2

• Most patients with functional esophageal disorders achieve adequate symptom control at 10–30 mg daily in real-world practice, even though clinical trials have used higher doses. 2

• The analgesic and neuromodulatory effects are independent of antidepressant action and typically require 2–4 weeks to become apparent. 2

Maximum Dose Recommendations

• Target a maximum of 25–30 mg daily for globus sensation, as the evidence supports efficacy at this low dose and higher doses increase cardiovascular risk without proven additional benefit for functional esophageal symptoms. 2, 3

• The American Gastroenterological Association recommends a maximum of 30–50 mg at night for functional gastrointestinal disorders, with dose titration by 10 mg per week or fortnight. 1

• Do not exceed 100 mg/day due to dose-dependent risk of sudden cardiac death, particularly in patients with cardiovascular disease. 2

Special Population Considerations

Elderly Patients (≥65 years)

• Use approximately 50% of the standard adult dose, with a recommended ceiling of 10–15 mg daily initially, as older adults have increased susceptibility to anticholinergic toxicity and altered drug metabolism. 2

• If higher doses are needed, consider switching to nortriptyline, a secondary-amine tricyclic with fewer anticholinergic effects while maintaining equivalent efficacy. 2, 4

Patients with Cardiac Disease or Age >40 Years

• Obtain a baseline electrocardiogram (ECG) before initiating therapy; amitriptyline is contraindicated if PR or QTc intervals are prolonged. 2

• Absolute contraindications include recent myocardial infarction, clinically significant arrhythmias, and any degree of heart block. 2

• Limit the dose to 25 mg daily and avoid exceeding 100 mg/day to prevent dose-dependent cardiovascular toxicity (AV-node conduction delay, QTc prolongation). 2

Monitoring and Side Effects

• Common anticholinergic side effects include dry mouth (most frequent), constipation, sedation, blurred vision, and urinary retention. 1, 2, 3

• In the globus pharyngeus trial, dry mouth, sleepiness, dizziness, and constipation were the most common side effects, but the medication was well tolerated at 25 mg. 3

• Assess treatment response after 3–7 days for initial symptom improvement and after 4 weeks for full therapeutic effect on globus symptoms and quality of life. 3

Clinical Pearls and Common Pitfalls

• Do not rapidly escalate the dose; gradual titration improves tolerability and persistence with therapy. 2

• Do not skip the baseline ECG in patients ≥40 years or with known cardiac disease, as amitriptyline prolongs QTc interval and delays AV-node conduction in a dose-dependent manner. 2

• Do not assume higher doses are necessary; the single high-quality RCT in globus pharyngeus showed excellent efficacy at 25 mg, and most functional GI patients achieve adequate control at 10–30 mg daily. 2, 3

• The therapeutic effect on globus sensation includes improvement in sleep quality and quality of life measures (general health, vitality, social functioning, mental health), not just symptom reduction. 3

• If no response after 4 weeks at 25–30 mg, reassess the diagnosis rather than escalating to higher doses, as globus sensation may have alternative etiologies (anxiety, reflux, structural lesions). 3