Effect of Ivermectin Treatment on the Frequency of Seizures in Persons with Epilepsy Infected with Onchocerca volvulus

Abstract

A clinical trial performed in the Democratic Republic of Congo (DRC), among persons with epilepsy (PWE) infected with Onchocerca volvulus treated with anti-seizure medication suggested that ivermectin reduces the seizure frequency. We assessed the effect of ivermectin treatment on seizure frequency in PWE with and without anti-seizure medication in three onchocerciasis endemic areas (Maridi, South Sudan; Aketi, DRC; and Mahenge, Tanzania). Pre- and 3–5 months post-ivermectin microfilariae densities in skin snips and seizure frequency were assessed. After ivermectin, the median (IQR) percentage reduction in seizure frequency in the study sites ranged from 73.4% (26.0–90.0) to 100% (50.0–100.0). A negative binomial mixed model showed that ivermectin significantly reduced the seizure frequency, with a larger decrease in PWE with a high baseline seizure frequency. Mediation analysis showed that ivermectin reduced the seizure frequencies indirectly through reduction in microfilariae densities but also that ivermectin may have a direct anti-seizure effect. However, given the short half-life of ivermectin and the fact that ivermectin does not penetrate the healthy brain, such a direct anti-seizure effect is unlikely. A randomized controlled trial assessing the ivermectin effect in people infected with O. volvulus who are also PWE on a stable anti-seizure regimen may be needed to clarify the causal relationship between ivermectin and seizure frequency.

Nodding Syndrome: Clinical Characteristics, Risks Factors, Access to Treatment, and Perceptions in the Greater Mundri Area, South Sudan

“…A possible explanation for this may be that ivermectin is believed by the affected communities to improve the NS outcome. Also, a recent study in onchocerciasis-endemic areas in sub-Saharan Africa suggested that ivermectin intake reduced seizure frequency in persons with epilepsy who are infected with O. volvulus [ 21 ]. Additionally, children with NS, because of their disabilities, may be more likely to be at home during ivermectin distribution compared to healthy controls.…”

Anticonvulsant effects of ivermectin on pentylenetetrazole- and maximal electroshock-induced seizures in mice: the role of GABAergic system and KATP channels

“…In addition to the importance of molecular pathways investigation, from a clinical point of view the administration of IVM as an adjuvant therapy in epileptic patients suffering from parasitic diseases is also being investigated. In clinical studies, it has been determined that the coadministration of IVM in combination with drugs such as phenobarbital with GABAergic effects, can reduce the occurrence of seizures in these patients [ 26 , 28 , 66 ]. Therefore, it is very important to find drug interactions in order to make the treatment more effective, and additional studies in this field seem necessary.…”

Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

“…However, ivermectin, an FDA‐approved drug, exerts as an activator of GIRK channel subunits (Chen et al, 2017; Su et al., 2016). Clinical studies have revealed that ivermectin can reduce the frequency of seizures and provide adjuvant therapy for refractory epilepsy (Diazgranados‐Sanchez et al., 2017; Dusabimana et al., 2020; Mandro et al., 2020). Ivermectin can also prevent SUDEP and cardiac disorders accompanying seizures by regulating cardiac IKACh current.…”