Beneficial and adverse psychotropic effects of antiepileptic drugs in patients with epilepsy: a summary of prevalence, underlying mechanisms and data limitations

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.