What is the recommended treatment for functional dyspepsia, acotiamide or domperidone?

Acotiamide vs Domperidone for Functional Dyspepsia

Neither acotiamide nor domperidone can be strongly recommended as first-line prokinetic therapy for functional dyspepsia based on current evidence, as both have only weak recommendations with low-quality evidence; however, acotiamide is better studied specifically for postprandial distress syndrome (PDS) symptoms and has a superior safety profile compared to domperidone's cardiac risks. 1

Evidence Quality and Guideline Recommendations

The 2022 British Society of Gastroenterology guidelines explicitly state that prokinetics have variable efficacy and provide only a weak recommendation with low-quality evidence specifically for acotiamide (along with itopride and mosapride). 1 Notably, domperidone is not mentioned in these most recent high-quality guidelines, which is a significant omission given its historical use.

When to Consider Prokinetics in the Treatment Algorithm

Prokinetics should only be considered after first-line therapies have failed, which include: 1

• H. pylori eradication (if positive) - strong recommendation, high-quality evidence 1
• Proton pump inhibitors (PPIs) - strong recommendation, high-quality evidence 1
• Histamine-2 receptor antagonists - weak recommendation, low-quality evidence 1

Tricyclic antidepressants (TCAs) are the preferred second-line therapy with a strong recommendation and moderate-quality evidence, starting with amitriptyline 10 mg once daily and titrating to 30-50 mg daily. 1, 2

Acotiamide: Evidence and Clinical Profile

Efficacy Data

• Acotiamide 100 mg three times daily is the established dose with demonstrated efficacy in phase III trials, showing overall treatment efficacy of 52.2% versus 34.8% for placebo. 3
• Specifically effective for postprandial distress syndrome (PDS) symptoms including postprandial fullness, early satiation, and upper abdominal bloating (RR 1.29,95% CI 1.09-1.53). 4
• Not effective for epigastric pain syndrome (EPS) symptoms (RR 0.92,95% CI 0.76-1.11). 4
• An extended-release formulation (300 mg once daily) shows comparable efficacy to the three-times-daily dosing with responder rates >92%. 5

Safety Profile

• Excellent long-term safety demonstrated in 1-year open-label trials with 81.6% of patients maintaining treatment for >50 weeks. 6
• No treatment-related severe or serious adverse events, no deaths, and no clinically significant laboratory abnormalities in long-term studies. 6
• Most common adverse event is headache (7.9-9.2% of patients). 5
• No cardiac safety concerns reported. 6, 7

Mechanism

Acotiamide works as an acetylcholinesterase inhibitor that enhances gastric accommodation and fundic relaxation after eating, addressing the pathophysiology of PDS. 3, 7

Domperidone: Critical Safety Concerns

Domperidone is notably absent from the 2022 BSG guidelines, which is significant given that these are the most recent high-quality guidelines available. This omission likely reflects growing concerns about its safety profile, particularly:

• Cardiac risks including QT prolongation and potential for serious arrhythmias
• Regulatory restrictions in many countries due to these safety concerns
• Limited availability outside certain regions

Clinical Decision Algorithm

Step 1: First-Line Therapy

• Test and treat for H. pylori if positive 1
• Trial of PPI therapy (lowest effective dose) 1

Step 2: Assess Symptom Pattern

• If PDS symptoms predominate (postprandial fullness, early satiation, bloating): Consider acotiamide 100 mg three times daily if available 3, 4
• If EPS symptoms predominate (epigastric pain): Continue acid suppression or move to TCAs 4

Step 3: Second-Line Therapy (Preferred)

• Initiate amitriptyline 10 mg once daily in the evening, titrate slowly to 30-50 mg daily 1, 2
• Counsel patients this is used as a gut-brain neuromodulator, not as an antidepressant 2

Step 4: Refractory Disease

• Multidisciplinary team involvement 1
• Consider antipsychotics (sulpiride, levosulpiride) 1
• Early dietitian involvement 1

Critical Caveats

Availability is a major limitation: Acotiamide is primarily available in Japan and some Asian countries, while domperidone has restricted availability in many Western countries due to safety concerns. 1

The evidence base for all prokinetics in FD is weak, and the guidelines emphasize this limitation explicitly. 1

Geographic considerations matter: Many prokinetics mentioned in guidelines are "unavailable outside of Asia and the USA." 1

If neither agent is available or appropriate, move directly to TCAs as second-line therapy rather than pursuing other prokinetics with even less evidence. 1, 2