Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation

Tergau, Frithjof; Wischer, Stephan; Somal, Hardyal S; Nitsche, Michael A.; Mercer, A. J.; Paulus, Walter; Steinhoff, Bernhard J.

doi:10.1016/j.eplepsyres.2003.08.006

Cited by 55 publications

(34 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study was limited by the lack of a placebo group. However, we doubt this confounded our results, because prior placebo-controlled studies have not shown significant changes in these measures due to placebo or time (Reis et al, 2002;Tergau et al, 2003). Moreover, time did not influence thresholds (see Table 1) and the crossover design means that we had two opportunities to observe prepost time effects, one on each medication, in each subject, and found no evidence of such effects.…”

Section: Discussionmentioning

confidence: 79%

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Gilbert

Ridel

Sallee

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Stimulant and norepinephrine (NE) reuptake inhibitor medications have different effects at the neuronal level, but both reduce symptoms of attention deficit hyperactivity disorder (ADHD). To understand their common physiologic effects and thereby gain insight into the neurobiology of ADHD treatment, we compared the effects of the stimulant methylphenidate (MPH) and NE uptake inhibitor atomoxetine (ATX) on inhibitory and excitatory processes in human cortex. Nine healthy, right-handed adults were given a single, oral dose of 30 mg MPH and 60 mg ATX at visits separated by 1 week in a randomized, double-blind crossover trial. We used paired and single transcranial magnetic stimulation (TMS) of motor cortex to measure conditioned and unconditioned motor-evoked potential amplitudes at inhibitory (3 ms) and facilitatory (10 ms) interstimulus intervals (ISI) before and after drug administration. Data were analyzed with repeated measures, mixed model regression. We also analyzed our findings and the published literature with meta-analysis software to estimate treatment effects of stimulants and NE reuptake inhibitors on these TMS measures. There were no significant pretreatment differences or effects of treatment order. Both agents produced a significant increase in facilitation and a decrease in inhibition. Effects of ATX and MPH did not differ significantly. Pooled estimates from published studies show similar results for stimulants and NE reuptake inhibitors. In conclusion, in healthy adults, both stimulant and nonstimulant medications for ADHD decrease cortical inhibition and increase cortical facilitation. Cortical inhibition, shown previously to be abnormal in ADHD, may play a key role producing behavioral pathology.

show abstract

Section: Discussionmentioning

confidence: 79%

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Gilbert

Ridel

Sallee

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…The subjects received either a single oral dose of 325 mg of LTG or placebo on the first visit, and then on the second visit they were given whatever they did not initially receive. A single oral dose of 325 mg of LTG has been shown to produce, at 3 h, serum concentrations equal to steady-state levels at clinically relevant chronic doses (Tergau et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

Interleaved Transcranial Magnetic Stimulation/Functional MRI Confirms that Lamotrigine Inhibits Cortical Excitability in Healthy Young Men

Tenebäck

Nahas

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

Little is known about how lamotrigine (LTG) works within brain circuits to achieve its clinical effects. We wished to determine whether the new technique of interleaved transcranial magnetic stimulation (TMS)/functional magnetic resonance imaging (fMRI) could be used to assess the effects of LTG on activated motor or prefrontal/limbic circuits. We carried out a randomized, double-blind, crossover trial involving two visits 1 week apart with TMS measures of cortical excitability and blood oxygen level-dependent TMS/fMRI. Subjects received either a single oral dose of 325 mg of LTG or placebo on each visit. In all, 10 subjects provided a complete data set that included interleaved TMS/fMRI measures and resting motor threshold (rMT) determinations under both placebo and LTG conditions. A further two subjects provided only rMT data under the two drug conditions. LTG caused a 14.979.6% (mean7SD) increase in rMT 3 h after the drug, compared with a 0.6710.9% increase 3 h after placebo (t ¼ 3.41, df ¼ 11, po0.01). fMRI scans showed that LTG diffusely inhibited cortical activation induced by TMS applied over the motor cortex. In contrast, when TMS was applied over the prefrontal cortex, LTG increased the TMS-induced activation of limbic regions, notably the orbitofrontal cortex and hippocampus. These results suggest that LTG, at clinically relevant serum concentrations, has a general inhibitory effect on cortical neuronal excitability, but may have a more complex effect on limbic circuits. Furthermore, the interleaved TMS/fMRI technique may be a useful tool for investigating regional brain effects of psychoactive compounds.

show abstract

“…Measurements of cortical excitability with TMS have demonstrated increasing promise for quantifying the central effects of CNS-active drugs in humans: It was not only possible to classify antiepileptic drugs according to their effects on motor cortex excitability (Ziemann et al 1996), but also to correlate drug serum levels with their effects on cortical excitability (Chen et al 1997;Tergau et al 2003). Accordingly, drug-induced alterations of cortical excitability have been proposed as biomarkers, which may be further developed to predict optimal antiepileptic drug treatment for a given patient (Tergau et al 2003;Ziemann et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Modulation of human motor cortex excitability by quetiapine

et al. 2007

View full text Add to dashboard Cite

By lengthening CSP without affecting MT, ICI and ICF, quetiapine demonstrates a unique neurophysiological profile which differs distinctively from brain excitability profiles of typical antipsychotics such as haloperidol. Provided that the CSP prolongation reflects the antipsychotic potential of quetiapine, TMS may be developed as a tool to monitor neurobiological effects of quetiapine treatment in schizophrenic patients and to explore the efficacy of other antipsychotic drugs with a similar mode of action.

show abstract

Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation

Cited by 55 publications

References 26 publications

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Interleaved Transcranial Magnetic Stimulation/Functional MRI Confirms that Lamotrigine Inhibits Cortical Excitability in Healthy Young Men

Modulation of human motor cortex excitability by quetiapine

Contact Info

Product

Resources

About