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Introduction: The use of topiramate has increased in recent years. It is now used in several specialties to treat a wide range of medical conditions. A small number of case reports describes psychosis as an adverse event of topiramate. While using topiramate as an option for treatment-resistant epilepsy, clinicians need to be aware of the possibility of topiramate-induced psychosis in patients who have not previously had a psychotic episode. Although there is a small literature in neurology journals regarding psychiatric adverse events in epileptic patients, the psychiatric literature is silent about the topic. We report a patient without a previous history of psychosis, who developed psychosis after use of topiramate.
Case: The patient on multiple antiepileptic drugs with refractory tonic-clonic epilepsy was prescribed topiramate. The patient developed definite psychotic symptoms including auditory halucinations and paranoid-persecutory delusions and other behavioral symptoms fifteen days after beginning topiramate. The psychotic and other psychiatric symptoms resolved quickly with discontinuation of topiramate and by using a second-generation antpsychotic drug.
Discussion: Topiramate was originally discovered as an oral hypoglycaemic, afterwards was approved as an anticonvulsant agent and is now used as an adjunct to various treatments. The several mechanisms of action include inhibition of sodium conductance, decreased frequency of generated action potentials, activated gamma-aminobutyric acid activity, inhibition of AMPA receptor, and weak inhibition of carbonic anhydrase (1). The mechanism underlying psychotic symptoms induced by topiramate is not clear, but overactivity of ascending dopaminergic pathways due to GABAergic inhibition of the substantia nigra has been proposed (3). The true prevalence of topiramate-induced psychosis is not known. Although there have only been a few case reports of topiramate-induced psychosis, an antiepileptic drug survey group found the incidence to be 1.5% in 596 patients (2). The risk of this side effect may be greater in the general population as studies of topiramate exclude patients with past psychiatric history and past psychiatric history is the most important predictor for psychiatric adverse events. As epilepsy could overlap with psychiatric conditions at a rate of 50-60% including mood, anxiety, and psychotic disorders, clinicians should be cautious in diagnosing drug–induced psychosis.