Trial reportBritish journal of clinical pharmacology2022
Transcranial magnetic stimulation as biomarker of excitability in drug development: A randomized, double-blind, placebo-controlled, cross-over study.
Trial report in British journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Transcranial magnetic stimulation-evoked electroencephalography responses as biomarkers for epilepsy: A review of study design and outcomes.Human brain mapping · 2023Pooled it
- Sustained pharmacodynamic effects of S-ketamine on cortical excitability and resting-state brain activity: A randomized, placebo-controlled trial.British journal of clinical pharmacology · 2026Trial
- Transcranial Magnetic Stimulation as a Translational Biomarker in Early-Phase Anti-Seizure Medication Development: A Randomized, Double-Blind, Placebo-Controlled Study in Generalized Epilepsy.Clinical pharmacology and therapeutics · 2026Trial
- Cannabidiol Lacks Direct Effect on Cortical Excitability: A Randomized, Double Blind, Placebo Controlled, 3-Way Crossover Trial.Clinical pharmacology and therapeutics · 2026Trial
- TMS and EEG Pharmacodynamic Effects of a Selective Sphingosine-1-Phosphate Subtype 1 Receptor Agonist on Cortical Excitability in Healthy Subjects.Clinical pharmacology and therapeutics · 2025Trial
- Transcranial magnetic stimulation as biomarker of excitability in drug development: A randomized, double-blind, placebo-controlled, cross-over study.British journal of clinical pharmacology · 2022Trial
- Impact of cenobamate on cortical responses to transcranial magnetic stimulation in people with drug-resistant focal epilepsy.Epilepsia open · 2026Article
- Utilization of Single-Pulse Transcranial-Evoked Potentials in Neurological and Psychiatric Clinical Practice: A Narrative Review.Neurology international · 2024Review
- Neural Circuitry-Related Biomarkers for Drug Development in Psychiatry: An Industry Perspective.Advances in neurobiology · 2024Review
- Reducing motor evoked potential amplitude variability through normalization.Frontiers in psychiatry · 2024Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe purpose of this study was to investigate pharmacodynamic effects of drugs targeting cortical excitability using transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and electroencephalography (EEG) in healthy subjects, to further develop TMS outcomes as biomarkers for proof-of-mechanism in early-phase clinical drug development. Antiepileptic drugs presumably modulate cortical excitability. Therefore, we studied effects of levetiracetam, valproic acid and lorazepam on cortical excitability in a double-blind, placebo-controlled, 4-way cross-over study.
methodsIn 16 healthy male subjects, single- and paired-pulse TMS-EMG-EEG measurements were performed predose and 1.5, 7 and 24 hours postdose. Treatment effects on motor-evoked potential, short and long intracortical inhibition and TMS-evoked potential amplitudes, were analysed using a mixed model ANCOVA and cluster-based permutation analysis.
resultsWe show that motor-evoked potential amplitudes decreased after administration of levetiracetam (estimated difference [ED] -378.4 μV; 95%CI: -644.3, -112.5 μV; P < .01), valproic acid (ED -268.8 μV; 95%CI: -532.9, -4.6 μV; P = .047) and lorazepam (ED -330.7 μV; 95%CI: -595.6, -65.8 μV; P = .02) when compared with placebo. Long intracortical inhibition was enhanced by levetiracetam (ED -60.3%; 95%CI: -87.1%, -33.5%; P < .001) and lorazepam (ED -68.2%; 95%CI: -94.7%, -41.7%; P < .001) at a 50-ms interstimulus interval. Levetiracetam increased TMS-evoked potential component N45 (P = .004) in a central cluster and decreased N100 (P < .001) in a contralateral cluster.
conclusionThis study shows that levetiracetam, valproic acid and lorazepam decrease cortical excitability, which can be detected using TMS-EMG-EEG in healthy subjects. These findings provide support for the use of TMS excitability measures as biomarkers to demonstrate pharmacodynamic effects of drugs that influence cortical excitability.
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