Seizure · 2026
Acetazolamide in drug-resistant epilepsy: a systematic review with meta-analysis.
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Mehta Amar A, Arasu Shanjali Arulmozhi, Lasker Bruce R
Аннотация
BACKGROUND: Drug-resistant epilepsy (DRE) remains a high-morbidity condition despite expanding antiseizure medications. Acetazolamide (ACZ), a carbonic anhydrase inhibitor introduced for epilepsy in the 1950s, has been largely displaced by newer agents and concerns about tolerance, but its low cost and pH-mediated mechanism support reassessment in select DRE contexts.
METHODS: We conducted a PROSPERO-registered, PRISMA-S-informed systematic review of clinical studies evaluating ACZ as mono- or adjunctive therapy for drug-resistant or refractory epilepsy through May 11, 2026. Risk of bias was assessed using Newcastle-Ottawa and ROBINS-I frameworks. To quantify treatment efficacy random-effects generalized linear mixed-model meta-analyses estimated seizure freedom and ≥50% responder rate.
RESULTS: Twenty-six studies were included. The pooled seizure-freedom proportion was 25.7% (95% CI, 15.8%-38.9%; k = 20; I² = 89.5%) and ≥50% responder proportion 67.5% (95% CI, 48.2%-82.2%; k = 26; I² = 96.7%). Leave-one-out analysis did not identify a single influential study nor did exploratory meta-regression show a significant age-response correlation. Phenotype-specific and narrative findings demonstrated more consistent response in certain catamenial, spike-wave, photosensitive, genetic, and metabolic epilepsy contexts. Metabolic acidosis, nephrolithiasis, and treatment discontinuation were comparatively uncommon, whereas adverse effects were predominantly tolerability-related.
CONCLUSION: ACZ retains a measurable but selective antiseizure signal in DRE. However, limitations in decades-old reporting, considerable between-study heterogeneity, limited controlled clinical evidence, and modest sample sizes in phenotype-specific cohorts require researchers to interpret the evidence with caution. Nevertheless, ACZ's observed clinical activity, low cost, and distinct mechanism of action make it a promising candidate for prospective studies to identify responsive epilepsy types, assess the durability of benefit, and redefine its place in modern epilepsy care.
METHODS: We conducted a PROSPERO-registered, PRISMA-S-informed systematic review of clinical studies evaluating ACZ as mono- or adjunctive therapy for drug-resistant or refractory epilepsy through May 11, 2026. Risk of bias was assessed using Newcastle-Ottawa and ROBINS-I frameworks. To quantify treatment efficacy random-effects generalized linear mixed-model meta-analyses estimated seizure freedom and ≥50% responder rate.
RESULTS: Twenty-six studies were included. The pooled seizure-freedom proportion was 25.7% (95% CI, 15.8%-38.9%; k = 20; I² = 89.5%) and ≥50% responder proportion 67.5% (95% CI, 48.2%-82.2%; k = 26; I² = 96.7%). Leave-one-out analysis did not identify a single influential study nor did exploratory meta-regression show a significant age-response correlation. Phenotype-specific and narrative findings demonstrated more consistent response in certain catamenial, spike-wave, photosensitive, genetic, and metabolic epilepsy contexts. Metabolic acidosis, nephrolithiasis, and treatment discontinuation were comparatively uncommon, whereas adverse effects were predominantly tolerability-related.
CONCLUSION: ACZ retains a measurable but selective antiseizure signal in DRE. However, limitations in decades-old reporting, considerable between-study heterogeneity, limited controlled clinical evidence, and modest sample sizes in phenotype-specific cohorts require researchers to interpret the evidence with caution. Nevertheless, ACZ's observed clinical activity, low cost, and distinct mechanism of action make it a promising candidate for prospective studies to identify responsive epilepsy types, assess the durability of benefit, and redefine its place in modern epilepsy care.