Journal of Neurology

, Volume 264, Issue 5, pp 921–927 | Cite as

Brain tumor location influences the onset of acute psychiatric adverse events of levetiracetam therapy: an observational study

  • Vincenzo BelcastroEmail author
  • Laura Rosa Pisani
  • Silvio Bellocchi
  • Paolo Casiraghi
  • Gaetano Gorgone
  • Marco Mula
  • Francesco Pisani
Original Communication


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.


Tumor frontal lobe location Epilepsy Levetiracetam Psychiatric adverse events 


Compliance with ethical standards

Conflicts of interest

MM has received consultancy fees from UCB Pharma, Eisai, Pfizer and Elsevier and has also received supports from Bial and Special Products Ltd. Vincenzo Belcastro, Laura Rosa Pisani, Paolo Casiraghi, Silvio Bellocchi, Gaetano Gorgone, Francesco Pisani declare that they have not conflict of interest.

Ethical standards

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.


This manuscript received no funding.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Neurology UnitS. Anna HospitalComoItaly
  2. 2.Neurology Unit“Cutrona Zodda” HospitalBarcellona Pozzo di GottoItaly
  3. 3.Neurosurgery UnitS. Anna HospitalComoItaly
  4. 4.Neurology UnitS. Giovanni di Dio HospitalCrotoneItaly
  5. 5.Atkinson Morley Regional Neuroscience Centre, St George’s University Hospitals, NHS Foundation Trust and Institute of Medical and Biomedical SciencesSt George’s University of LondonLondonUK
  6. 6.Department of Experimental and Clinical MedicineUniversity of MessinaMessinaItaly

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