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Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials.
Epilepsia 2017; 58(1):42-50E

Abstract

OBJECTIVE

Antiepileptic drug (AED) treatment failures may occur because there is insufficient drug in the brain or because of a lack of relevant therapeutic response. Until now it has not been possible to measure these factors. It has been recently shown that the combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) can measure the effects of drugs in healthy volunteers. TMS-evoked EEG potentials (TEPs) comprise a series of positive and negative deflections that can be specifically modulated by drugs with a well-known mode of action targeting inhibitory neurotransmission. Therefore, we hypothesized that TMS-EEG can detect effects of two widely used AEDs, lamotrigine and levetiracetam, in healthy volunteers.

METHODS

Fifteen healthy subjects participated in a pseudo-randomized, placebo-controlled, double-blind, crossover design, using a single oral dose of lamotrigine (300 mg) and levetiracetam (3,000 mg). TEPs were recorded before and 120 min after drug intake, and the effects of drugs on the amplitudes of TEP components were statistically evaluated.

RESULTS

A nonparametric cluster-based permutation analysis of TEP amplitudes showed that AEDs both increased the amplitude of the negative potential at 45 msec after stimulation (N45) and suppressed the positive peak at 180 msec (P180). This is the first demonstration of AED-induced modulation of TMS-EEG measures.

SIGNIFICANCE

Despite the different mechanism of action that lamotrigine and levetiracetam exert at the molecular level, both AEDs impact the TMS-EEG response in a similar way. These TMS-EEG fingerprints observed in healthy subjects are candidate predictive markers of treatment response in patients on monotherapy with lamotrigine and levetiracetam.

Authors+Show Affiliations

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.School of Psychology, University of East London (UEL), London, United Kingdom.Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

27808418

Citation

Premoli, Isabella, et al. "Lamotrigine and Levetiracetam Exert a Similar Modulation of TMS-evoked EEG Potentials." Epilepsia, vol. 58, no. 1, 2017, pp. 42-50.
Premoli I, Biondi A, Carlesso S, et al. Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials. Epilepsia. 2017;58(1):42-50.
Premoli, I., Biondi, A., Carlesso, S., Rivolta, D., & Richardson, M. P. (2017). Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials. Epilepsia, 58(1), pp. 42-50. doi:10.1111/epi.13599.
Premoli I, et al. Lamotrigine and Levetiracetam Exert a Similar Modulation of TMS-evoked EEG Potentials. Epilepsia. 2017;58(1):42-50. PubMed PMID: 27808418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials. AU - Premoli,Isabella, AU - Biondi,Andrea, AU - Carlesso,Sara, AU - Rivolta,Davide, AU - Richardson,Mark P, Y1 - 2016/11/03/ PY - 2016/10/07/accepted PY - 2016/11/4/pubmed PY - 2017/6/22/medline PY - 2016/11/4/entrez KW - Antiepileptic drug KW - Electroencephalography KW - Epilepsy KW - Pharmaco-TMS-EEG KW - Transcranial magnetic stimulation SP - 42 EP - 50 JF - Epilepsia JO - Epilepsia VL - 58 IS - 1 N2 - OBJECTIVE: Antiepileptic drug (AED) treatment failures may occur because there is insufficient drug in the brain or because of a lack of relevant therapeutic response. Until now it has not been possible to measure these factors. It has been recently shown that the combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) can measure the effects of drugs in healthy volunteers. TMS-evoked EEG potentials (TEPs) comprise a series of positive and negative deflections that can be specifically modulated by drugs with a well-known mode of action targeting inhibitory neurotransmission. Therefore, we hypothesized that TMS-EEG can detect effects of two widely used AEDs, lamotrigine and levetiracetam, in healthy volunteers. METHODS: Fifteen healthy subjects participated in a pseudo-randomized, placebo-controlled, double-blind, crossover design, using a single oral dose of lamotrigine (300 mg) and levetiracetam (3,000 mg). TEPs were recorded before and 120 min after drug intake, and the effects of drugs on the amplitudes of TEP components were statistically evaluated. RESULTS: A nonparametric cluster-based permutation analysis of TEP amplitudes showed that AEDs both increased the amplitude of the negative potential at 45 msec after stimulation (N45) and suppressed the positive peak at 180 msec (P180). This is the first demonstration of AED-induced modulation of TMS-EEG measures. SIGNIFICANCE: Despite the different mechanism of action that lamotrigine and levetiracetam exert at the molecular level, both AEDs impact the TMS-EEG response in a similar way. These TMS-EEG fingerprints observed in healthy subjects are candidate predictive markers of treatment response in patients on monotherapy with lamotrigine and levetiracetam. SN - 1528-1167 UR - https://www.unboundmedicine.com/medline/citation/27808418/Lamotrigine_and_levetiracetam_exert_a_similar_modulation_of_TMS_evoked_EEG_potentials_ L2 - https://doi.org/10.1111/epi.13599 DB - PRIME DP - Unbound Medicine ER -