Rapid titration of VNS therapy reduces time-to-response in epilepsy
Tzadok M, Verner R, Kann L, Tungala D, Gordon C, El Tahry R, Fahoum F.
Epilepsy Behav. 2022 Sep;134:108861.
https://doi.org/10.1016/j.yebeh.2022.108861
Traditional dose titration for vagus nerve stimulation (#VNS) Therapy in drug-resistant epilepsy (#DRE) is generally performed in small increments over an extended period (usually months). While this allows for close assessments of VNS tolerability, it may also substantially delay target dosing and some patients may not reach target dosing before the common efficacy follow-up 12 months post-implantation.
This new publication by Tzadok 𝘦𝘵 𝘢𝘭. 2022 retrospectively analyzed the relationship between time to the target dose* (fast: <3 months, medium: 3-6 months, or slow: >6 months) and the time to VNS response (≥50% reduction in seizure frequency) based on data from 12 clinical studies (N= 651 adults and 344 children). The study further examined patient #tolerability and safety based on the different titration regimens.
𝐇𝐢𝐠𝐡𝐥𝐢𝐠𝐡𝐭𝐬
- 𝐑𝐚𝐩𝐢𝐝 𝐭𝐢𝐭𝐫𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐕𝐍𝐒 𝐩𝐚𝐫𝐚𝐦𝐞𝐭𝐞𝐫 𝐬𝐞𝐭𝐭𝐢𝐧𝐠𝐬 𝐫𝐞𝐬𝐮𝐥𝐭𝐬 𝐢𝐧 𝐚 𝐟𝐚𝐬𝐭𝐞𝐫 𝐨𝐧𝐬𝐞𝐭 𝐨𝐟 𝐜𝐥𝐢𝐧𝐢𝐜𝐚𝐥 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞
- 𝐂𝐮𝐦𝐮𝐥𝐚𝐭𝐢𝐯𝐞 𝐦𝐞𝐚𝐧 𝐚𝐝𝐯𝐞𝐫𝐬𝐞 𝐞𝐯𝐞𝐧𝐭𝐬 𝐝𝐨 𝐧𝐨𝐭 𝐜𝐨𝐫𝐫𝐞𝐥𝐚𝐭𝐞 𝐰𝐢𝐭𝐡 𝐭𝐢𝐭𝐫𝐚𝐭𝐢𝐨𝐧 𝐭𝐢𝐦𝐞 𝐢𝐧 𝐩𝐞𝐝𝐢𝐚𝐭𝐫𝐢𝐜 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬
- 𝐓𝐡𝐞 𝐬𝐢𝐝𝐞 𝐞𝐟𝐟𝐞𝐜𝐭 𝐩𝐫𝐨𝐟𝐢𝐥𝐞 𝐚𝐩𝐩𝐞𝐚𝐫𝐬 𝐭𝐨 𝐛𝐞 𝐜𝐨𝐦𝐩𝐚𝐫𝐚𝐛𝐥𝐞 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐝𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐭 𝐭𝐢𝐭𝐫𝐚𝐭𝐢𝐨𝐧 𝐬𝐩𝐞𝐞𝐝𝐬
Cox weighted regression analysis revealed a significant relation between titration time and time to response. Furthermore, adverse events appeared to be more common in adults undergoing rapid titration, whereas adverse events were comparable between different titration regimens in children.
Despite limitations, such as the influence of possible antiepileptic drug (#AED) changes during follow-up, the current data suggest that rapid titration of VNS parameters results in a faster response onset and should be considered when deciding on a titration strategy. Especially in pediatric patients where the side effect profile is comparable between titration regimens.
*The target dose was empirically defined as 1.625 mA, 250 µs, and 20 Hz.
