Systematic Review Weighs Acetazolamide's Role in Drug-Resistant Epilepsy

A systematic review with meta-analysis on acetazolamide in drug-resistant epilepsy appeared online on 8 October 2026 in Seizure: European Journal of Epilepsy, authored by Amar A. Mehta, Shanjali Arulmozhi Arasu and Bruce R. Lasker.

For a drug that clinicians have prescribed for decades, the surprise is not the drug itself. It is that drug-resistant epilepsy — seizures persisting despite adequate trials of at least two antiseizure medications — still lacks a settled answer on where acetazolamide belongs in the sequence.

The review addresses precisely that gap. The authors pooled the available literature on acetazolamide, a carbonic anhydrase inhibitor, in patients whose seizures failed standard pharmacotherapy, synthesizing comparative evidence through formal meta-analytic methods rather than narrative summary.

Why does this matter at the reading bench?

Acetazolamide has long lived in the grey zone of epilepsy practice. Neurologists reach for it in catamenial epilepsy, in refractory absence seizures, and as an add-on when options narrow — often on tradition rather than on pooled estimates of effect.

A meta-analysis changes the terms of that conversation. It converts scattered, individually underpowered studies into a single quantitative signal that clinicians in epilepsy monitoring units and outpatient follow-up can weigh when adjusting regimens for patients who fail two or more drugs.

For electroencephalographers specifically, the practical stakes are concrete. Add-on decisions in drug-resistant patients frequently coincide with requests for repeat scalp EEG to characterize remaining seizure types or to evaluate surgical candidacy. A clearer evidence base for acetazolamide sharpens the clinical question those recordings answer: whether persistent epileptiform patterns reflect an inadequate regimen or true pharmacoresistance.

What kind of evidence was synthesized?

The work is a systematic review with meta-analysis — the highest tier of evidence short of new randomized trials. Mehta, Arasu and Lasker structured the analysis around the drug-resistant population, which the field defines by the ILAE criteria of failure of at least two appropriately chosen and tolerated antiseizure medications.

Readers should note what this publication is not. It reports no new primary patient data, no new device findings, and no monitoring technology claims. Its contribution is interpretive: aggregating prior studies of acetazolamide into estimates that individual trials, often small, could not deliver on their own.

The full effect estimates, subgroup analyses and heterogeneity statistics appear in the article itself, available online through Seizure since 8 October 2026.

How should practitioners position the findings?

For clinicians managing drug-resistant epilepsy, the review offers a consolidated reference point for a medication that has never held first-line status yet never left the formulary. Any meta-analytic verdict on seizure reduction or retention carries direct weight in shared decision-making with patients who have exhausted mainstream options.

For clinical neurophysiologists, the downstream implication concerns patient flow. Patients with drug-resistant epilepsy occupy a large share of long-term video-EEG monitoring beds, and pharmacologic evidence that shifts add-on strategies — even marginally — alters how long patients remain medical candidates before intracranial evaluation enters the discussion.

The review arrives amid persistent interest in repurposing established drugs for refractory populations, where the cost and safety profiles of older agents carry practical advantages over novel compounds.

Whether the pooled evidence is sufficient to formalize acetazolamide's place in drug-resistant treatment algorithms — or merely to expose the thinness of the underlying trial base — is the question the full text answers, and the question subsequent trial design will need to address.