Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy

Hirsch, Lawrence J.; Weintraub, David; Du, Yunling; Buchsbaum, Richard; Spencer, H. T.; Hager, Melissa; Straka, Tara; Bazil, Carl W.; Adams, David J.; Resor, Stanley R.; Morrell, Martha J.

doi:10.1212/01.wnl.0000138424.33979.0c

Cited by 92 publications

(80 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These cultures yielded virtually pure neurons (Supplementary Figure 2). Doses of drugs chosen were based on their therapeutic plasma concentrations clinically (Groeneveld et al, 2003;Hirsch et al, 2004;Zarate et al, 2005). Thus, concentrations of lamotrigine (20 mM), riluzole (2.0 mM), and valproate (1.0 mM) were chosen for our studies.…”

Section: Neuronal Culture Preparationsmentioning

confidence: 99%

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

Suzuki

Wei

et al. 2006

Neuropsychopharmacol

192

153

View full text Add to dashboard Cite

A growing body of data suggests that the glutamatergic system may be involved in the pathophysiology and treatment of severe mood disorders. Chronic treatment with the antimanic agents, lithium and valproate, resulted in reduced synaptic expression of the AMPA(-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subunit GluR1 in the hippocampus, while treatment with an antidepressant (imipramine) enhanced the synaptic expression of GluR1. The anticonvulsants, lamotrigine (6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine) and riluzole (2-amino-6-trifluoromethoxybenzothiazole), have been demonstrated to have efficacy in the depressive phase of bipolar disorder. We therefore sought to determine the role of these anticonvulsants, compared to that of the predominantly antimanic anticonvulsant valproate, on AMPA receptor localization. We found that the agents with a predominantly antidepressant profile, namely lamotrigine and riluzole, significantly enhanced the surface expression of GluR1 and GluR2 in a time-and dose-dependent manner in cultured hippocampal neurons. By contrast, the predominantly antimanic agent, valproate, significantly reduced surface expression of GluR1 and GluR2. Concomitant with the GluR1 and GluR2 changes, the peak value of depolarized membrane potential evoked by AMPA was significantly higher in lamotrigine-and riluzole-treated neurons, supporting the surface receptor changes. Phosphorylation of GluR1 at the PKA (cAMP-dependent protein kinase) site (S845) was enhanced in both lamotrigine-and riluzoletreated hippocampal neurons, but reduced in valproate-treated neurons. In addition, lamotrigine and riluzole, as well as the traditional antidepressant imipramine, also increased GluR1 phosphorylation at GluR1 (S845) in the hippocampus after chronic in vivo treatment. Our findings suggest that regulation of GluR1/2 surface levels and function may be responsible for the different clinical profile of anticonvulsants (antimanic or antidepressant), and may suggest avenues for the development of novel therapeutics for these illnesses.

show abstract

Section: Neuronal Culture Preparationsmentioning

confidence: 99%

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

Suzuki

Wei

et al. 2006

Neuropsychopharmacol

192

153

View full text Add to dashboard Cite

show abstract

“…The overall clinical significance of lamotrigine serum concentrations has been demonstrated recently, with lamotrigine tolerability highly correlated with lamotrigine serum concentration. 15 Given this relationship, the effect of comedication on lamotrigine CL can be important for clinical care.…”

Section: Commentmentioning

confidence: 99%

Effect of Antiepileptic Drug Comedication on Lamotrigine Clearance

Weintraub

Buchsbaum²,

Resor³

et al. 2005

Arch Neurol

View full text Add to dashboard Cite

To investigate the effect of antiepileptic drug (AED) comedication, including all newer AEDs, on lamotrigine clearance (CL).Design: We reviewed 570 medical charts of outpatients 12 years and older seen at the Columbia Comprehensive Epilepsy Center who received lamotrigine as monotherapy or adjunctive therapy. We investigated whether a given comedication contributed to the lamotrigine serum concentration. In addition, we examined whether the mean lamotrigine CL during comedication with each AED differed from the lamotrigine CL during monotherapy. Finally, we examined whether individuals had significantly different lamotrigine CLs when taking or not taking a particular comedication.Results: Comedication with phenytoin, carbamazepine, and valproate sodium were the major AED predictors of lamotrigine serum concentration. Comedication regimens with felbamate, oxcarbazepine, and phenobarbital were small but significant predictors. The mean lamotrigine CL was 43.2 mL/h per kilogram of body weight with lamotrigine monotherapy, significantly higher with comedication with phenytoin (101.3 mL/h per kilogram) and carbamazepine (59.5 mL/h per kilogram) and significantly lower with valproate (16.9 mL/h per kilogram). Patients had significantly higher lamotrigine CL when taking phenytoin, carbamazepine, and phenobarbital than when not taking those comedications and had significantly lower lamotrigine CL when taking valproate. The mean lamotrigine CL was significantly lower than that associated with monotherapy in patients comedicated with valproate plus phenytoin (22.0 mL/h per kilogram) but not in patients comedicated with valproate plus carbamazepine (33.3 mL/h per kilogram). No other AEDs affected lamotrigine CL. Conclusion:Phenytoin increases lamotrigine CL by approximately 125%, carbamazepine increases lamotrigine CL by approximately 30% to 50%, and valproate decreases lamotrigine CL by approximately 60%. No newer AED, with the possible exception of oxcarbazepine, has a major impact on lamotrigine CL.

show abstract

“…[1][2][3] In contrast, Johannessen and Tomson 4) reported that TDM was likely to be useful for treatment with LTG in many clinical settings. Hirsch et al 5) also reported that the incidence of side effects caused by LTG increased along with elevation of its concentration. According to this report, full seizure control could be obtained for a 6-month period by maintaining plasma LTG concentrations above 20 μg/mL.…”

mentioning

confidence: 96%

Influence of Concomitant Antiepileptic Drugs on Plasma Lamotrigine Concentration in Adult Japanese Epilepsy Patients

Yamamoto

Inoue

Matsuda

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy

Cited by 92 publications

References 22 publications

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

Effect of Antiepileptic Drug Comedication on Lamotrigine Clearance

Influence of Concomitant Antiepileptic Drugs on Plasma Lamotrigine Concentration in Adult Japanese Epilepsy Patients

Contact Info

Product

Resources

About