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The Long-Term Safety of Antiepileptic Drugs

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Abstract

Antiepileptic drugs (AEDs) are used by millions of people worldwide for the treatment of epilepsy, as well as in many other neurological and psychiatric conditions. They are frequently associated with adverse effects (AEs), which have an impact on the tolerability and success of treatment. Half the people who develop intolerable AEs discontinue treatment early on after initiation, while the majority of people will continue to be exposed to their effects for long periods of time. The long-term safety of AEDs reflects their potential for chronic, cumulative dose effects; rare, but potentially serious late idiosyncratic effects; late, dose-related effects; and delayed, teratogenic or neurodevelopmental effects. These AEs can affect every body system and are usually insidious. With the exception of delayed effects, most other late or chronic AEs are reversible. To date, there is no clear evidence of a carcinogenic effect of AEDs in humans. While physicians are aware of the long-term AEs of old AEDs (the traditional liver enzyme-inducing AEDs and valproate), information about AEs of new AEDs (such as lamotrigine, levetiracetam, oxcarbazepine, topiramate or zonisamide), particularly of their teratogenic effects, has emerged over the years. Sporadic publications have raised issues about AEs of the newer AEDs eslicarbazepine, retigabine, rufinamide, lacosamide and perampanel but their long-term safety profiles may take years to be fully appreciated. Physicians should not only be aware of the late and chronic AEs of AEDs but should systematically enquire and screen for these according to the individual AED AE profile. Care should be taken for individuals with comorbid conditions that may render them more susceptible to specific AEs. Prevention and appropriate management of long-term AED AEs is expected to improve adherence to treatment, quality of life and control of epilepsy.

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Acknowledgments

The authors report no conflict of interest in relation to this work. It was partly undertaken at University College Hospitals/University College London, which receives a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. No other sources of funding were used in the preparation of this review. JWS has received honoraria for consulting and lecturing from GSK, UCB and Viropharma; serves on the editorial boards for the Lancet Neurology and Epileptic Disorders; and has received research support from the Epilepsy Society, the Marvin Weil Epilepsy Research Fund, The European Union FP7 Programme, Eisai, GSK, UCB, the World Health Organization, National Institutes of Health and Nationaal Epilepsie Fonds Nederland. The authors are grateful to Dr. Gail Bell for her thorough review of the manuscript and valuable comments.

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Gaitatzis, A., Sander, J.W. The Long-Term Safety of Antiepileptic Drugs. CNS Drugs 27, 435–455 (2013). https://doi.org/10.1007/s40263-013-0063-0

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