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April 07, 2009; 72 (14) Articles

Adverse antiepileptic drug effects

Toward a clinically and neurobiologically relevant taxonomy

Piero Perucca, Jewell Carter, Victoria Vahle, Frank G. Gilliam
First published April 6, 2009, DOI: https://doi.org/10.1212/01.wnl.0000345667.45642.61
Piero Perucca
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Jewell Carter
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Victoria Vahle
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Frank G. Gilliam
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Citation
Adverse antiepileptic drug effects
Toward a clinically and neurobiologically relevant taxonomy
Piero Perucca, Jewell Carter, Victoria Vahle, Frank G. Gilliam
Neurology Apr 2009, 72 (14) 1223-1229; DOI: 10.1212/01.wnl.0000345667.45642.61

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Abstract

Background: Adverse effects (AEs) of antiepileptic drugs (AEDs) are a major impediment to optimal dosing for seizure control. Better understanding of clinical properties of AEs is a prerequisite for systematic research of their neurobiological underpinnings. This study aimed to define specific patterns of AE occurrence and determine their clinical relevance based on their association with subjective health status.

Methods: Two hundred subjects with epilepsy completed validated self-report health assessments, including the Adverse Event Profile (AEP) and Quality of Life in Epilepsy Inventory (QOLIE)-89. Factor analysis was performed on the 19 AEP items to identify distinct classes of AEs. Correlations between AE class scores and QOLIE-89 scores were evaluated. Multivariate analysis was used to assess contributions of AE class scores to QOLIE-89 scores after controlling for depression and seizure frequency. Relationships between changes in AE class scores and changes in QOLIE-89 scores were also investigated in a subgroup of 62 subjects enrolled in a randomized trial.

Results: The mean number of AEs per subject was 6.5. AEs were segregated into five classes: Cognition/Coordination, Mood/Emotion, Sleep, Weight/Cephalgia, and Tegument/Mucosa. Higher scores in each AE class were associated with lower QOLIE-89 scores. Cognition/Coordination scores were the strongest predictor of QOLIE-89 scores. Improvements in Cognition/Coordination, Mood/Emotion, and Tegument/Mucosa scores were associated with improvements in QOLIE-89 scores. Improved Cognition/Coordination was the only predictor of improved QOLIE-89.

Conclusion: Adverse effects (AEs) of antiepileptic drugs can be classified in five biologically plausible factors. When specific classes of AEs are identified and attempts are made to reduce them, quality of life is significantly improved.

AE = adverse effect; AED = antiepileptic drug; AEP = Adverse Event Profile; BDI = Beck Depression Inventory; GABA = γ-aminobutyric acid; HRQOL = Health-Related Quality of Life; QOLIE = Quality of Life in Epilepsy Inventory.

Footnotes

  • piero.perucca{at}libero.it

    Supplemental data at www.neurology.org

    Supported by NIH grants NS40808 and NS047551 (research and salary support for F.G.G.).

    Disclosure: The authors report no disclosures.

    Medications: Carbamazepine (Tegretol®; Novartis Pharmaceutical Corporation, East Hanover, NJ); lamotrigine (Lamictal®; GlaxoSmithKline, Research Triangle Park, NC); phenytoin (Dilantin®; Parke-Davis, New York, NY); valproate (Depakene®; Abbott Laboratories, North Chicago, IL); levetiracetam (Keppra®; UCB, Smyrna, GA).

    Received September 16, 2008. Accepted in final form January 5, 2009.

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