Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy

L. J. Hirsch, D. Weintraub, Y. Du, R. Buchsbaum, H. T. Spencer, M. Hager, T. Straka, C. W. Bazil, D. J. Adams, S. R. Resor, M. J. Morrell

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Abstract

Objective: To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy. Methods: The charts of 811 outpatients with epilepsy who had received LTG and were seen at the Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels. Results: In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic and 30.7% of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels (p < 0.0001): With levels <5.0 μg/mL, 7% of patients were toxic; with levels of 5 to 10 μg/mL, 14%; with 10 to 15 μg/mL, 24%; with 15 to 20 μg/mL, 34%; and with >20 μg/mL, 59%. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of >20 μg/mL. Conclusions: There is a correlation between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 μg/mL) and occur in only 7.4% of patients at levels obtained during the majority of clinical trials (<5 μg/mL). An initial target range of 1.5 to 10 μg/mL is suggested, though higher levels, up to >20 μg/mL, are often tolerated and can lead to additional efficacy in refractory patients.

Original languageEnglish
Pages (from-to)1022-1026
Number of pages5
JournalNeurology
Volume63
Issue number6
StatePublished - Sep 29 2004
Externally publishedYes

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Epilepsy
Serum
Poisons
Anticonvulsants
lamotrigine
Drug-Related Side Effects and Adverse Reactions
Seizures
Outpatients

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hirsch, L. J., Weintraub, D., Du, Y., Buchsbaum, R., Spencer, H. T., Hager, M., ... Morrell, M. J. (2004). Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy. Neurology, 63(6), 1022-1026.

Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy. / Hirsch, L. J.; Weintraub, D.; Du, Y.; Buchsbaum, R.; Spencer, H. T.; Hager, M.; Straka, T.; Bazil, C. W.; Adams, D. J.; Resor, S. R.; Morrell, M. J.

In: Neurology, Vol. 63, No. 6, 29.09.2004, p. 1022-1026.

Research output: Contribution to journalArticle

Hirsch, LJ, Weintraub, D, Du, Y, Buchsbaum, R, Spencer, HT, Hager, M, Straka, T, Bazil, CW, Adams, DJ, Resor, SR & Morrell, MJ 2004, 'Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy', Neurology, vol. 63, no. 6, pp. 1022-1026.
Hirsch LJ, Weintraub D, Du Y, Buchsbaum R, Spencer HT, Hager M et al. Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy. Neurology. 2004 Sep 29;63(6):1022-1026.
Hirsch, L. J. ; Weintraub, D. ; Du, Y. ; Buchsbaum, R. ; Spencer, H. T. ; Hager, M. ; Straka, T. ; Bazil, C. W. ; Adams, D. J. ; Resor, S. R. ; Morrell, M. J. / Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy. In: Neurology. 2004 ; Vol. 63, No. 6. pp. 1022-1026.
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abstract = "Objective: To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy. Methods: The charts of 811 outpatients with epilepsy who had received LTG and were seen at the Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels. Results: In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4{\%} were toxic and 30.7{\%} of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels (p < 0.0001): With levels <5.0 μg/mL, 7{\%} of patients were toxic; with levels of 5 to 10 μg/mL, 14{\%}; with 10 to 15 μg/mL, 24{\%}; with 15 to 20 μg/mL, 34{\%}; and with >20 μg/mL, 59{\%}. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of >20 μg/mL. Conclusions: There is a correlation between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 μg/mL) and occur in only 7.4{\%} of patients at levels obtained during the majority of clinical trials (<5 μg/mL). An initial target range of 1.5 to 10 μg/mL is suggested, though higher levels, up to >20 μg/mL, are often tolerated and can lead to additional efficacy in refractory patients.",
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AU - Weintraub, D.

AU - Du, Y.

AU - Buchsbaum, R.

AU - Spencer, H. T.

AU - Hager, M.

AU - Straka, T.

AU - Bazil, C. W.

AU - Adams, D. J.

AU - Resor, S. R.

AU - Morrell, M. J.

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N2 - Objective: To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy. Methods: The charts of 811 outpatients with epilepsy who had received LTG and were seen at the Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels. Results: In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic and 30.7% of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels (p < 0.0001): With levels <5.0 μg/mL, 7% of patients were toxic; with levels of 5 to 10 μg/mL, 14%; with 10 to 15 μg/mL, 24%; with 15 to 20 μg/mL, 34%; and with >20 μg/mL, 59%. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of >20 μg/mL. Conclusions: There is a correlation between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 μg/mL) and occur in only 7.4% of patients at levels obtained during the majority of clinical trials (<5 μg/mL). An initial target range of 1.5 to 10 μg/mL is suggested, though higher levels, up to >20 μg/mL, are often tolerated and can lead to additional efficacy in refractory patients.

AB - Objective: To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy. Methods: The charts of 811 outpatients with epilepsy who had received LTG and were seen at the Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels. Results: In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic and 30.7% of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels (p < 0.0001): With levels <5.0 μg/mL, 7% of patients were toxic; with levels of 5 to 10 μg/mL, 14%; with 10 to 15 μg/mL, 24%; with 15 to 20 μg/mL, 34%; and with >20 μg/mL, 59%. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of >20 μg/mL. Conclusions: There is a correlation between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 μg/mL) and occur in only 7.4% of patients at levels obtained during the majority of clinical trials (<5 μg/mL). An initial target range of 1.5 to 10 μg/mL is suggested, though higher levels, up to >20 μg/mL, are often tolerated and can lead to additional efficacy in refractory patients.

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