Can Ivermectin Cause Toxic Encephalopathy?
Yes, ivermectin can cause toxic encephalopathy, particularly in patients co-infected with Loa loa (loiasis) who have high microfilarial loads, but encephalopathy has also been reported outside endemic regions and with overdoses of both veterinary and human formulations.
Primary Risk: Loa loa Co-infection
The most well-established mechanism of ivermectin-induced encephalopathy occurs in patients with onchocerciasis who are heavily co-infected with Loa loa:
Patients with Loa loa microfilarial counts >8,000/ml (and especially >50,000/ml) are at high risk for developing serious or fatal encephalopathy following ivermectin treatment 1, 2, 3.
The FDA drug label explicitly warns that patients heavily infected with Loa loa "may develop a serious or even fatal encephalopathy either spontaneously or following treatment with an effective microfilaricide" 2.
Clinical manifestations include confusion, lethargy, stupor, seizures, coma, pain (neck and back), red eye, conjunctival hemorrhage, dyspnea, urinary/fecal incontinence, and difficulty standing or walking 2.
Onset typically occurs 3-4 days after ivermectin administration 3.
Geographic and Clinical Context
While initially described in Central and West African loiasis-endemic regions, encephalopathies have been reported from outside loiasis-endemic areas as well (adjusted reporting odds ratio 6.30,95% CI: 2.68-14.8 compared to benzimidazole drugs) 4.
A systematic pharmacovigilance study found increased reporting of encephalopathies and confusional disorders after ivermectin compared to other antinematodal drugs globally, not just in sub-Saharan Africa 4.
Overdose-Related Encephalopathy
Toxic encephalopathy can occur with supratherapeutic dosing:
Patients taking veterinary formulations for COVID-19 developed neurotoxicity including altered mental status at higher rates than those taking prescription tablets 5.
Ivermectin penetrates the mammalian brain poorly under normal circumstances, but at high doses or with blood-brain barrier impairment, it can exert neurotoxic effects 6.
In a series of 37 COVID-19-related ivermectin toxicity cases, 30 patients developed neurotoxicity, with those taking veterinary products experiencing more severe altered mental status 5.
Management Considerations
For patients requiring ivermectin in Loa loa-endemic areas:
Pretreatment assessment for loiasis with blood microfilarial counts is mandatory 2.
If microfilariae are present on blood film, corticosteroids should be used in conjunction with treatment 1.
Careful post-treatment follow-up and monitoring is essential 2.
For established encephalopathy:
Early hospitalization and supportive care are critical—patients with early intervention recovered within 2-3 days of altered consciousness, while delayed management led to fatal outcomes 3.
Corticosteroid treatment should be administered emergently, as inflammatory processes appear central to the pathophysiology 7.
Clinical examination may normalize after one month, but EEG abnormalities can persist for 5-7 months 3.
Important Caveats
Patients with severe liver disease may be at increased risk for toxicity, as safety in this population is not well-established 8, 9.
The syndrome is rare but serious—over 12 million people have received ivermectin for onchocerciasis with the vast majority experiencing no serious adverse reactions 3.
Standard therapeutic dosing (200-250 μg/kg) for approved parasitic infections rarely causes encephalopathy in patients without Loa loa co-infection 8.