Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial

PLoS Negl Trop Dis. 2020 Jan 10;14(1):e0007966. doi: 10.1371/journal.pntd.0007966. eCollection 2020 Jan.


Introduction: Recent findings from onchocerciasis-endemic foci uphold that increasing ivermectin coverage reduces the epilepsy incidence, and anecdotal evidence suggests seizure frequency reduction in persons with onchocerciasis-associated epilepsy, when treated with ivermectin. We conducted a randomized clinical trial to assess whether ivermectin treatment decreases seizure frequency.

Methods: A proof-of-concept randomized clinical trial was conducted in the Logo health zone in the Ituri province, Democratic Republic of Congo, to compare seizure frequencies in onchocerciasis-infected persons with epilepsy (PWE) randomized to one of two treatment arms: the anti-epileptic drug phenobarbital supplemented with ivermectin, versus phenobarbital alone. The primary endpoint was defined as the probability of being seizure-free at month 4. A secondary endpoint was defined as >50% reduction in seizure frequency at month 4, compared to baseline. Both endpoints were analyzed using multiple logistic regression. In longitudinal analysis, the probability of seizure freedom during the follow-up period was assessed for both treatment arms by fitting a logistic regression model using generalized estimating equations (GEE).

Results: Ninety PWE enrolled between October and November 2017 were eligible for analysis. A multiple logistic regression analysis showed a borderline association between ivermectin treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062). There was no significant difference in the probability of experiencing >50% reduction of the seizure frequency at month 4 between the two treatment arms. Also, treatment with ivermectin did not significantly increase the odds of being seizure-free during the individual follow-up visits.

Conclusion: Whether ivermectin has an added value in reducing the frequency of seizures in PWE treated with AED remains to be determined. A larger study in persons with OAE on a stable AED regimen and in persons with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with OAE.

Trial registration: Registration: www.clinicaltrials.gov; NCT03052998.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / therapeutic use*
  • Antiparasitic Agents / administration & dosage
  • Antiparasitic Agents / therapeutic use
  • Democratic Republic of the Congo / epidemiology
  • Drug Therapy, Combination
  • Epilepsy / drug therapy*
  • Epilepsy / epidemiology
  • Epilepsy / etiology*
  • Female
  • Humans
  • Ivermectin / administration & dosage
  • Ivermectin / therapeutic use*
  • Male
  • Onchocerciasis / complications*
  • Onchocerciasis / drug therapy*
  • Onchocerciasis / epidemiology
  • Young Adult


  • Anticonvulsants
  • Antiparasitic Agents
  • Ivermectin

Associated data

  • ClinicalTrials.gov/NCT03052998

Grant support

RC received a European Research Council grant No. 671055 (https://erc.europa.eu/). The funder did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.