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Acetazolamide causes an acidification of the intracellular and extracellular environments activating acid\u2010sensing ion channels, and these may account for the anti\u2010seizure effects of acetazolamide. Other potential mechanisms are modulation of neuroinflammation and attenuation of high\u2010frequency oscillations. The overall effect increases the seizure threshold in critical structures such as the hippocampus. The evidence for its clinical efficacy was from 12 observational studies of 941 patients. The 50% responder rate was 49%, 20% of patients were rendered seizure\u2010free, and 30% were noted to have had at least one adverse event. We conclude that the evidence from several observational studies may overestimate efficacy because they lack a comparator; hence, this drug would need further randomized placebo\u2010controlled trials to assess effectiveness and harm.<\/jats:p>","DOI":"10.1002\/epi4.12619","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T04:09:47Z","timestamp":1654661387000},"page":"378-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Acetazolamide: Old drug, new evidence?"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-0386","authenticated-orcid":false,"given":"Arif Ali","family":"Shukralla","sequence":"first","affiliation":[{"name":"The National Epilepsy Programme Beaumont Hospital Dublin 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