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Impact of Drug Manipulation on Seizure Freedom in Adults with Uncontrolled Epilepsy: A Prospective Controlled Study in Rural China

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Abstract

Introduction

It has been suggested that uncontrolled epilepsy might not necessarily equate to drug resistance when antiepileptic drugs (AEDs) are used at relatively low doses, a practice frequently observed in rural areas of China.

Objective

To assess the clinical benefits of further drug manipulation in this situation, we prospectively followed up the outcomes of patients with uncontrolled epilepsy while taking relatively low doses of AEDs.

Methods

The study included patients aged 16 years and older with uncontrolled epilepsy and who were receiving at least one AED at a dosage below 50% of the World Health Organization (WHO) defined daily dose (DDD) (50% DDD) (Group 1). Patients with drug-resistant epilepsy were included for comparison (Group 2). Both groups were followed-up for at least 2 years. Seizure outcomes after further drug manipulations were recorded at the last follow-up.

Results

A total of 197 patients (55.3% male) were included in Group 1 and 32 (46.9% male) in Group 2; their mean duration of follow-up was 28.85 ± 1.90 and 30.91 ± 2.04 months, respectively. At the last follow-up, 16.8% (33/197) of patients in Group 1 had become seizure-free compared with none in Group 2 (p < 0.001). Seventeen of 93 (18.3%) patients in Group 1 became seizure free after increasing the dosage of baseline AED(s) alone. Only 5.5% (3/55) of patients who had failed to respond to an AED at ≥50% DDD at baseline became seizure free compared with 21.1% (30/142) who did not have such a history (p = 0.001). The number of AEDs taken at a dosage below 50% DDD at baseline was not associated with seizure outcome.

Conclusions

Uncontrolled epilepsy could become controlled in a substantial proportion of patients by dose increase alone, particularly if there is no history of drug failure at ≥50% DDD.

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Author Contributions

Xiaoting Hao: study concept and design, acquisition of data, statistical analysis, drafting of the manuscript. Ziyi Chen: drafting of the manuscript, analysis and interpretation of data. Bo Yan: acquisition of data. Patrick Kwan: study concept, interpretation of data, critical revision of manuscript for intellectual content. Dong Zhou: study supervision, study concept and design, interpretation of data, critical revision of manuscript for intellectual content.

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    Authors and Affiliations

    1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610000, China

      Xiaoting Hao, Bo Yan & Dong Zhou

    2. Department of Neurology, The First Affiliated Hospital Sun Yat-sen University, Guangzhou, China

      Ziyi Chen

    3. Departments of Medicine and Neurology, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia

      Patrick Kwan

    4. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

      Patrick Kwan

    5. Department of Neurology, Royal Melbourne Hospital, Parkville, Melbourne, 3050, VIC, Australia

      Patrick Kwan

    Authors
    1. Xiaoting Hao
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    Corresponding authors

    Correspondence to Patrick Kwan or Dong Zhou.

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    Funding

    This study was partly supported by the National Natural Science Foundation of China, No: 81301677 (to XTH).

    Conflicts of interest

    Dr. Kwan has received research grants from the National Health and Medical Research Council of Australia, Australian Research Council, US National Institutes of Health, Hong Kong Research Grants Council, Innovation and Technology Fund, Health and Health Services Research Fund, and Health and Medical Research Fund. He/his institution also received speaker or consultancy fees and/or research grants from Eisai, GlaxoSmithKline, Johnson & Johnson, Pfizer, and UCB Pharma. Drs. Xiaoting Hao, Ziyi Chen, Bo Yan, and Dong Zhou have no relevant conflicts of interest.

    Ethical approval

    The study was approved by the Institutional Ethics Committee of West China Hospital. All participants or their legal guardians provided written informed consent. The study was performed in accordance with ethics standards laid down in the 1964 Declaration of Helsinki and its later amendments.

    Additional information

    X. Hao and Z. Chen contributed equally to the manuscript.

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    Hao, X., Chen, Z., Yan, B. et al. Impact of Drug Manipulation on Seizure Freedom in Adults with Uncontrolled Epilepsy: A Prospective Controlled Study in Rural China. CNS Drugs 31, 237–243 (2017). https://doi.org/10.1007/s40263-016-0397-5

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    • DOI: https://doi.org/10.1007/s40263-016-0397-5

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