From the Guidelines
Ivermectin can potentially lower seizure threshold, especially in patients with high L. loa microfilaria loads, typically exceeding 8000 microfilaria/ml, as it may cause serious neurological adverse events that might lead to death 1. When considering ivermectin treatment, it is crucial to assess the risk of severe adverse events, particularly in areas co-endemic with onchocerciasis and loiasis. The risk of neurological adverse events, including seizures, is high when the microfilaria load exceeds 8000 microfilaria/ml, and the reaction is more severe if the load exceeds 30 000 microfilaria/ml 1. Key considerations for ivermectin treatment include:
- Assessing the microfilaria load before treatment to minimize the risk of severe adverse events
- Implementing close surveillance to manage severe adverse effects in areas where treatment is conducted
- Educating patients about the potential risks and benefits of ivermectin treatment to reduce refusal rates due to fear of adverse events
- Considering alternative treatment strategies for patients with high L. loa microfilaria loads or pre-existing seizure disorders
- Monitoring patients closely for neurological symptoms, such as tremors, dizziness, or altered consciousness, which could be precursors to seizure activity 1.
From the Research
Ivermectin Seizure Threshold
- The seizure threshold of ivermectin is not explicitly stated in the provided studies, but its effects on seizures and epilepsy are discussed 2, 3, 4.
- Ivermectin has been proposed as a potential treatment for epilepsy due to its antiparasitic and anti-inflammatory properties, but its efficacy and safety for this indication are still being researched 2, 3.
- Studies have shown that ivermectin may reduce seizure frequency in patients with onchocerciasis-associated epilepsy, but more research is needed to confirm its effectiveness 3, 4.
- The mechanism of action of ivermectin involves binding to ligand-gated ion channel receptors, including glutamate, GABA, and glycine, which may contribute to its potential anticonvulsant effects 5, 6.
- However, ivermectin's penetration into the mammalian brain is poor, and it may not exert significant pharmacological effects unless used at high, potentially toxic doses or in cases where the blood-brain barrier is impaired 2.
Potential Anticonvulsant Effects
- Ivermectin has demonstrated anticonvulsant effects against clonic and tonic-clonic seizures in some studies, possibly through modulation of the GABAA receptor and neuroinflammation 3.
- The combination of ivermectin with GABAergic anti-seizure medications like diazepam may have synergistic effects, but more research is needed to confirm this 3.
- Ivermectin's anti-inflammatory properties, including the inhibition of cytokines like TNF-α and IL-1β, may also contribute to its potential anticonvulsant effects 3, 6.
Clinical Trials and Studies
- A randomized proof-of-concept clinical trial found a borderline association between ivermectin treatment and being seizure-free at month 4 in patients with onchocerciasis-associated epilepsy, but the results were not statistically significant 4.
- Another study suggested that ivermectin may decrease seizure frequency in patients with onchocerciasis-associated epilepsy, but more research is needed to confirm its effectiveness 3.