What are documented outcomes and follow‑up durations in human case series of severe ivermectin overdose?
Executive summary
Human case series and reports of severe ivermectin overdose document a spectrum of outcomes ranging from full recovery after supportive care to prolonged neurologic injury and death; reported follow‑up intervals are heterogeneous and typically limited to the hospital stay or short outpatient reassessment rather than standardized long‑term surveillance [1] [2] [3]. Case series and pharmacovigilance reports emphasize frequent neurologic manifestations (confusion, ataxia, seizures, coma), cardiopulmonary complications such as hypotension and aspiration, and variable recovery timelines often measured in days to weeks; rare fatal and genetically mediated encephalopathic cases are documented [4] [2] [5].
1. Clinical outcomes recorded in case series: full recovery after supportive care is common but not universal
Multiple case reports and series describe patients who developed neurotoxic or gastrointestinal syndromes after supratherapeutic ivermectin exposure and recovered with supportive measures—examples include patients whose neurologic status resolved within 24–48 hours after activated charcoal and supportive care and who were discharged neurologically intact after hospital courses of several days [6] [7] [1]. Poison‑control and public‑health summaries also report that many overdose presentations result in improvement with time and supportive care, consistent with the toxicology literature describing primary CNS depression and GI effects that often abate as drug concentrations fall [1] [8].
2. Severe neurologic endpoints and genetic vulnerability: coma, encephalopathy, and ABCB1 mutations
Case series flag severe neurologic events—loss of consciousness, seizures, coma, and encephalopathy—as principal adverse outcomes of severe exposures, and molecular case work has linked catastrophic CNS toxicity in at least one child to biallelic or compound heterozygous loss‑of‑function variants in ABCB1 (the P‑glycoprotein transporter), implicating impaired blood–brain‑barrier efflux as an explanatory mechanism for some otherwise unexpected severe presentations [9] [5].
3. Fatalities and exceptional cases: documented deaths and marked heterogeneity of origin
Deaths after ivermectin misuse have been reported in the literature, including a documented fatal transdermal overdose that did not respond to hemoperfusion and cardiorespiratory support; such fatal reports are uncommon in the aggregate literature but demonstrate that lethal outcomes occur, particularly with extreme dosing, unusual routes of administration, or delayed presentation [3] [10]. Public‑health advisories and case series emphasize that veterinary formulations and inappropriate topical use have contributed to severe and sometimes fatal poisonings [4] [11].
4. Nonfatal severe complications beyond neurologic effects: cardiopulmonary and dermatologic outcomes
Severe overdoses are associated with hypotension, aspiration pneumonia after intubation or depressed consciousness, and serious cutaneous adverse reactions in some reports; the NEJM and public‑health case compilations list hypotension, ataxia, visual hallucinations, and need for hospitalization as recurring severe endpoints [2] [8]. Animal and experimental reports raise concerns about severe cutaneous adverse reactions and systemic toxicity with misuse, though human series vary in which complications are emphasized [12].
5. Documented follow‑up durations: short, variable, and often limited to hospital discharge
Follow‑up in published case series is inconsistent and typically short: several reports document recovery and no residual deficits on follow‑up after hospital stays of about 4–8 days (e.g., discharge on hospital day 4 after extubation; neurologic resolution by hospital day 2 and discharge after eight days) [7] [6]. Other reports record imaging or clinical reassessment within days to a week (for example, CT resolution after 7 days in a fatal transdermal case before death), but standardized long‑term outcome surveillance beyond weeks is generally absent from the case‑series literature [3] [10].
6. Reconciling high‑dose safety data with case‑series harms: context and limitations
Systematic reviews of planned high‑dose ivermectin in clinical trials report tolerability up to certain high doses (e.g., safety signals acceptable up to 800 µg/kg in trial contexts), yet real‑world case series document severe outcomes when veterinary formulations, extreme dosing, topical misuse, genetic susceptibility, or comorbidities are involved—highlighting an implicit agenda in trial literature toward controlled dosing safety and in case reports toward warning about misuse [13] [1]. Importantly, the literature lacks uniform definitions of “severe” poisoning and standardized, long‑term follow‑up protocols, which constrains precise estimates of persistent disability after overdose [6] [1].
7. Bottom line and evidence gaps
The documented outcomes in human case series span recovery with supportive care (often within days), prolonged critical illness and neurological complications, and rare deaths; follow‑up durations reported are mainly hospital‑centric (days to a few weeks) with sparse long‑term outcome data and no standardized post‑discharge surveillance across series, leaving the frequency of persistent neurologic or other sequelae after severe overdose unresolved in current reports [1] [7] [3].