What are the documented outcomes and long‑term neurologic sequelae in reported human cases of ivermectin neurotoxicity?
Executive summary
Documented human ivermectin neurotoxicity is uncommon but real: case series and pharmacovigilance reviews describe presentations ranging from confusion, ataxia and tremor to stupor and coma, sometimes with detection of drug in brain tissue, and most reports identify either overdose or host factors as likely contributors (ABCB1/mdr‑1 variants or high Loa loa microfilarial loads) [1] [2] [3]. Long‑term neurologic sequelae are infrequently reported in the literature; many described patients improved or recovered, but serious events including prolonged coma, recurrent episodes on re‑exposure, and deaths have been documented, and the quality and quantity of follow‑up data are limited [4] [1] [2].
1. Clinical picture and short‑term outcomes: what happens when toxicity occurs
Reports collated from case series, poison‑center surveillance during the COVID‑19 pandemic, and pharmacovigilance databases show a consistent toxidrome: neurologic manifestations such as confusion, encephalopathy, stupor, tremor, seizures and coma have been described, often accompanied by gastrointestinal complaints; patients who ingested supratherapeutic doses—especially veterinary formulations—tended to develop rapid onset neurotoxicity and a substantial minority required hospitalization [5] [4] [6]. Large case reviews identified dozens of suspected serious neurological adverse events reported outside onchocerciasis programs, with documented terms including “unable to walk,” “consciousness disturbed,” seizure, encephalopathy and coma, and a subset of patients showing severe courses requiring intensive care [1] [7].
2. Mechanisms and risk factors that shape outcome
Two dominant mechanisms recur across the literature: very high systemic exposure (overdose, particularly from veterinary products) and impaired blood–brain barrier efflux via dysfunction of the ABCB1/MDR1 P‑glycoprotein, whether from rare human nonsense mutations, genetic polymorphisms, drug interactions, or animal models that demonstrate dramatic brain accumulation when P‑gp is absent [5] [2] [3]. In addition, in onchocerciasis mass‑treatment programs, a well‑documented Loa loa microfilarial encephalopathy (PLERM) associated with very high L. loa burdens accounts for many severe cases after ivermectin, complicating attribution of direct drug neurotoxicity versus parasite‑related pathology [3] [8].
3. Evidence for long‑term neurologic sequelae: scarce, heterogenous, and inconclusive
Systematic case reviews and pharmacovigilance analyses find that while severe CNS events have occurred, clear, well‑documented persistent neurologic deficits are not frequently reported; several case reports describe resolution without residual deficits on follow‑up, but others report prolonged coma or recurrent toxicity on repeated exposure, and at least one case documented ivermectin presence in brain tissue—evidence compatible with a causal role in severe presentations [4] [1] [7] [2]. The literature repeatedly emphasizes that the number of credible cases is small relative to global exposure, that follow‑up data are uneven, and that alternative explanations (co‑infections, co‑morbidities, other drugs) were sometimes more plausible and therefore excluded from series [1] [8].
4. Prognosis and gaps in follow‑up: what the sources do — and do not — tell us
Poison‑center and clinical reports during the recent surge in ivermectin misuse indicate many patients improve with supportive care and decontamination measures and some recover fully without neurologic sequelae, but the datasets are biased toward acute care encounters and short‑term outcomes; robust prospective long‑term neurologic follow‑up is largely absent from the published series, leaving uncertainty about rare, delayed or subtle neurocognitive deficits after severe exposures [5] [4] [1]. Authors and reviewers explicitly warn that altered P‑gp function, co‑infection with L. loa, and reporting limitations confound causal statements and make population‑level risk quantification difficult [8] [3].
5. Practical interpretation: risk is real but rare; severe outcomes documented; long‑term risk uncertain
The balance of published evidence shows ivermectin can cause severe, sometimes fatal neurologic events in humans under specific circumstances—high doses, veterinary formulations, P‑gp dysfunction, or in the context of massive L. loa microfilaremia—while most therapeutic exposures do not produce such outcomes and many affected patients recover, but definitive statements about the frequency and nature of persistent long‑term neurologic sequelae cannot be made from the existing case series and pharmacovigilance data because of sparse, heterogeneous follow‑up and confounding by co‑morbid conditions [3] [1] [5] [8]. Continued vigilance, targeted pharmacogenetic inquiry into ABCB1 variants, systematic long‑term follow‑up of severe cases, and careful exclusion of alternative causes remain necessary to clarify the true burden of lasting neurologic harm [2] [9].