Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders

Antiepileptic drugs (AEDs) have various mechanisms of actions and therefore have diverse anticonvulsant, psychiatric, and adverse effect profiles. Two global categories of AEDs are identified on the basis of their predominant psychotropic profiles. One group has "sedating" effects in association wit h fatigue, cognitive slowing, and weight gain, as well as possible anxiolyt ic and antimanic effects. These actions may be related to a predominance of potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmissio n induced by drugs such as barbiturates, benzodiazepines, valproate, gabape ntin, tiagabine, and vigabatrin. The other group is associated with predomi nant attenuation of glutamate excitatory neurotransmission and has "activat ing" effects, with activation, weight loss, and possibly anxiogenic and ant idepressant effects. This group includes agents such as felbamate and lamot rigine. Agents such as topiramate, with both GABAergic and antiglutamatergi c actions, may have "mixed" profiles. Mechanisms of actions, activity in an imal models of anxiety and depression, and clinical psychotropic effects of AEDs in psychiatric and epilepsy patients are reviewed in relationship to this proposed categorization. These considerations suggest the testable hyp othesis that better psychiatric outcomes in seizure disorder patients could be achieved by treating patients with baseline "activated" profiles (insom nia, agitation, anxiety, racing thoughts, weight loss) with "sedating" pred ominantly GABAergic drugs, and conversely those with baseline "sedated" or anergic profiles (hypersomnia, fatigue, apathy, depression, sluggish cognit ion, weight gain) with "activating" predominantly antiglutamatergic agents. Systematic clinical investigation of more precise relationships of discret e mechanisms of actions to psychotropic profiles of AEDs is needed to asses s the utility of this general proposition and define exceptions to this bro ad principle.