What is the role of acetazolamide (carbonic anhydrase inhibitor) in the treatment of Meniere's disease?

Acetazolamide in Meniere's Disease

Acetazolamide is not recommended for the treatment of Meniere's disease due to insufficient evidence of efficacy and a high rate of adverse events (46-80% in clinical studies). 1, 2, 3

Guideline Position

The 2020 American Academy of Otolaryngology-Head and Neck Surgery clinical practice guideline for Meniere's disease does not include acetazolamide in its recommended treatment options. 1 The guideline specifically addresses:

• Diuretics and betahistine as maintenance therapy options (Statement 9) 1
• Intratympanic steroids for active disease not responsive to noninvasive treatment (Statement 11) 1
• Positive pressure therapy is explicitly recommended against (Statement 10) 1

Notably, acetazolamide is absent from these evidence-based recommendations, suggesting insufficient evidence to support its use. 1

Clinical Evidence Against Use

Efficacy Data

The most recent 2024 retrospective study of 15 Meniere's patients treated with acetazolamide (125-750 mg/day) found:

• 73% had decreased vertigo attacks 2
• No significant hearing recovery after treatment 2
• This conflicts with a 2023 Cochrane systematic review that found very low-certainty evidence for all systemic pharmacological interventions in Meniere's disease, preventing meaningful conclusions 4

Safety Concerns - The Critical Issue

Adverse events occur at an unacceptably high rate:

• 80% experienced paresthesias (numbness in hands, feet, or other body parts) in the 2024 study 2
• 33% discontinued medication after initial prescription due to side effects 2
• Hypokalemia with liver dysfunction occurred in one patient 2
• Hypokalemia with traumatic fracture from staggering occurred in another patient 2
• A 1984 study reported 46.2% significant adverse effects, including bilateral renal calculi requiring drug discontinuation 3

The 1984 study concluded definitively: "oral acetazolamide has no place in the medical treatment of Menière's disease" due to the high incidence of side-effects. 3

Mechanism and Theoretical Rationale

Acetazolamide theoretically could benefit Meniere's disease through:

• Carbonic anhydrase inhibition leading to acidification of the subretinal/endolymphatic space 1
• Potential reduction of endolymphatic hydrops (the presumed pathophysiology of Meniere's disease) 5
• A 1989 study showed 52% of patients had improved hearing thresholds 2 hours post-administration 5

However, theoretical mechanisms do not translate to clinically meaningful, sustained benefit with acceptable safety. 3, 4

Critical Safety Monitoring Required If Used

If acetazolamide is prescribed despite lack of guideline support, mandatory monitoring includes:

• Electrolyte panels (particularly potassium) due to hypokalemia risk 2
• Liver function tests due to hepatotoxicity risk 2
• Renal function assessment due to kidney stone risk 6
• Avoid co-prescription with licorice-containing medications (both cases of hypokalemia in the 2024 study involved concurrent Chinese herbal medicines with licorice) 2

Common dose-dependent side effects include paresthesias, vertigo, unpleasant taste, confusion, depression, and cognitive slowing. 6, 7

Contraindications

• Sulfonamide allergy (absolute contraindication) 6
• Severe liver disease 6
• Impaired renal function (use with extreme caution due to drug accumulation) 6
• Pregnancy (FDA Category C) 6

Recommended Alternative Approach

Based on the 2020 guideline, the evidence-based treatment algorithm for Meniere's disease should prioritize: 1

1. Dietary and lifestyle modifications (identifying individual triggers)
2. Diuretics and/or betahistine for maintenance therapy
3. Intratympanic steroids for active disease unresponsive to noninvasive treatment
4. Surgical options for refractory cases

Acetazolamide should be reserved only for research settings, similar to the European Respiratory Society's recommendation for its use in obstructive sleep apnea. 1