Ivermectin: a therapeutic strategy to treat patients with resistant epilepsy.

Drug-resistant epilepsy (DRE) remains a major clinical challenge, with up to one-third of patients experiencing uncontrolled seizures despite polytherapy. Ivermectin (IVM), a macrocyclic lactone with antiparasitic, neuromodulatory, and anti-inflammatory properties, has recently emerged as a candidate adjunctive therapy. We conducted an observational study including 146 patients with highly refractory epilepsy treated with IVM in addition to standard antiseizure medication (ASM). Clinical outcomes were assessed before and after IVM initiation, with seizure frequency recorded from patient diaries and seizure control classified according to International League Against Epilepsy criteria. IVM was administered orally, dissolved in propylene glycol, at doses ranging from 30 to 280 mg/week. After treatment, mean annual seizure frequency decreased by 88.9%, with consistent benefits across subgroups, including patients with cluster seizures (86.4% reduction). More than 90% of participants achieved seizure freedom, and all patients reported some degree of seizure reduction. Concomitant ASM burden decreased by 22%, reflecting improved tolerability and adherence, and no major safety concerns were observed. Mechanistically, the antiseizure potential of IVM may involve modulation of neuronal excitability, neuroinflammatory pathways, and blood-brain barrier transport dynamics, as supported by experimental evidence. These findings align with epidemiological data on onchocerciasis-associated epilepsy and recent controlled trials of IVM formulations in focal epilepsy. While further randomized studies are needed to confirm optimal dosing, safety monitoring, and mechanistic correlates, our results provide real-world evidence that IVM represents a promising adjunctive option for the management of refractory epilepsy.