To explore possible correlations among brain lesion location, development of psychiatric symptoms and the use of antiepileptic drugs (AEDs) in a population of patients with brain tumor and epilepsy. The medical records of 283 patients with various types of brain tumor (161 M/122 F, mean age 64.9 years) were analysed retrospectively. Patients with grade III and IV glioma, previous history of epileptic seizures and/or psychiatric disorders were excluded. Psychiatric symptoms occurring after initiation of AED therapy were considered as treatment emergent psychiatric adverse events (TE-PAEs) if they fulfilled the following conditions: (1) onset within 4 weeks after the beginning of AED therapy; (2) disappearance on drug discontinuation; (3) absence of any other identified possible concurrent cause. The possible influence of the following variables were analysed: (a) AED drug and dose; (b) location and neuroradiologic features of the tumor, (c) location and type of EEG epileptic abnormalities, (d) tumor excision already or not yet performed; (e) initiation or not of radiotherapy. TE-PAEs occurred in 27 of the 175 AED-treated patients (15.4%). Multivariate analysis showed a significant association of TE-PAEs occurrence with location of the tumor in the frontal lobe (Odds ratio: 5.56; 95% confidence interval 1.95-15.82; p value: 0.005) and treatment with levetiracetam (Odds ratio: 3.61; 95% confidence interval 1.48-8.2; p value: 0.001). Drug-unrelated acute psychiatric symptoms were observed in 4 of the 108 AED-untreated patients (3.7%) and in 7 of the 175 AED-treated patients (4%). The results of the present study suggest that an AED alternative to levetiracetam should be chosen to treat epileptic seizures in patients with a brain tumor located in the frontal lobe to minimize the possible onset of TE-PAEs.