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Beneficial and Adverse Psychotropic Effects of Antiepileptic Drugs in Patients with Epilepsy

A Summary of Prevalence, Underlying Mechanisms and Data Limitations

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Abstract

Antiepileptic drugs (AEDs) can have both beneficial and adverse psychotropic effects. They act on neurotransmitter systems, neuronal ion permeability and other targets, although the exact mechanisms are not generally fully elucidated. A systematic review of the literature reveals evidence for both positive and negative effects on depression, anxiety, aggression, psychosis and sleep in patients with epilepsy. Topiramate, vigabatrin, levetiracetam, tiagabine and zonisamide have been associated primarily with adverse psychotropic effects, whilst gabapentin, pregabalin, lacosamide and lamotrigine, in particular, have demonstrated a more beneficial psychotropic profile, especially with regard to affective symptoms. This review, however, identifies specific methodological issues with studies that have reported on the psychotropic effects of AEDs, suggesting that some of the findings might be inconclusive or unreliable because of confounding factors, particularly the presence of psychiatric history. More rigorous double-blind, randomized, placebo-controlled trials on larger numbers of patients with epilepsy, with clear inclusion/exclusion criteria, that are specifically designed to investigate psychotropic changes are more likely to produce results that inform clinical practice and direct future research.

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Acknowledgements

No funding has been received to prepare this review. Frank M.C. Besag has received lecture fees, consultancy fees, research grants and equipment grants from and has been sponsored to conferences by various pharmaceutical companies. He was previously editor-in-chief of a journal sponsored by GSK. None of these monies has been paid directly to Frank M.C. Besag; all monies since 2001 have been paid to NHS Trust. No monies are currently being received from pharmaceutical companies nor from any source other than Frank M.C. Besag’s employer, the NHS in the UK. Frank M.C. Besag has recently been sponsored to attend international epilepsy conferences by Eisai, the company that markets zonisamide and rufinamide in the UK.

The other authors have no conflicts of interest to report.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Birmingham and Solihull Mental Health Foundation Trust and University of Birmingham, Barberry Building, 25 Vincent Drive, Birmingham, B152FG, UK

    John Piedad, Hugh Rickards &  Andrea E. Cavanna MD, PhD

  2. Twinwoods Health Resource Centre, South Essex Partnership NHS Trust, Bedford, UK

    Frank M. C. Besag

  3. Department of Neuropsychiatry, Institute of Neurology and University College London, London, UK

    Andrea E. Cavanna MD, PhD

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Correspondence to Andrea E. Cavanna MD, PhD.

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Piedad, J., Rickards, H., Besag, F.M.C. et al. Beneficial and Adverse Psychotropic Effects of Antiepileptic Drugs in Patients with Epilepsy. CNS Drugs 26, 319–335 (2012). https://doi.org/10.2165/11599780-000000000-00000

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