The aim of this study was to analyze in detail psychopathology associated with topiramate (TPM) prescription and to analyze the relationship between psychopathology and seizure freedom. We analyzed the data on 103 patients who developed psychiatric disorders during TPM therapy. Forty-six patients developed an affective disorder, 22 aggressive behavior, 16 psychosis, 11 anxiety, and 8 personality changes such as anger, agitation, and hostile behavior. Patients with psychosis were more likely to be seizure-free during psychopathology, to receive psychotropic drug prescription, and to be admitted to hospital. In general, patients seizure-free during psychopathology were more likely to have a diagnosis of idiopathic generalized epilepsy, to be in co-therapy with vigabatrin, and to remit after drug reduction. We observed that psychopathology was related to seizure control in a subgroup of patients. The role of forced normalization, interlinked with interactions with other antiepileptic drugs, could be relevant.