Trial reportClinical pharmacology and therapeutics2026
Transcranial Magnetic Stimulation as a Translational Biomarker in Early-Phase Anti-Seizure Medication Development: A Randomized, Double-Blind, Placebo-Controlled Study in Generalized Epilepsy.
Trial report in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Clinical Pharmacology at the Point of Decision.Clinical pharmacology and therapeutics · 2026Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One-third of epilepsy patients remain treatment-resistant, underscoring the need for novel anti-seizure medications (ASMs) and reliable biomarkers of central target engagement. Cortical hyperexcitability is a hallmark of epilepsy, making excitability a valuable pharmacodynamic biomarker for early-phase drug development supporting go/no-go decision making. Building upon prior transcranial magnetic stimulation (TMS) work in healthy participants, this study aimed to establish TMS-derived endpoints as translational biomarkers of ASM effects in patients. In a randomized, double-blind, placebo-controlled, two-way crossover design, patients with generalized epilepsy on levetiracetam (500 mg twice daily; n = 14) or valproic acid (≤1,000 mg/day; levetiracetam-naïve, n = 12) received a single oral dose of levetiracetam (2000 mg) or placebo. Participants were asked to refrain from their morning ASM dose to minimize background ASM levels while maintaining seizure protection. TMS combined with electromyography (EMG) and electroencephalography (EEG), and resting-state EEG were performed pre-dose, 1.5 h, and 3 h post-dose. Outcomes were analyzed using mixed-effects analysis of covariance or cluster-based permutation testing. Levetiracetam significantly reduced motor-evoked potential (MEP) amplitude, enhanced long-interval intracortical inhibition (LICI), and increased frontal gamma and beta power, with larger effect sizes in levetiracetam-naïve patients. These findings were further supported by linear concentration-response relationships for these endpoints. TMS-EEG revealed group-specific modulation: early TMS-evoked potential components (P30/N45) in levetiracetam patients vs. later components (N100/P180) in levetiracetam-naïve patients. These findings build upon prior results, demonstrating that TMS-based biomarkers are sensitive to levetiracetam's acute effects in epilepsy patients with MEP amplitude, LICI, and frontal beta/gamma power emerging as promising biomarkers, possible also for new ASM development.
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