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

Abstract

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.

Effect of Antiepileptic Drugs in Glioma Patients on Self-reported Depression, Anxiety, and Cognitive Complaints 

“…Our results are in contrast with other studies in brain tumour patients, that demonstrated that LEV had an increased risk for psychiatric adverse effects, including anxiety. (16)(17)(18) This might be partly due to differences in patient populations, (17) the instrument used for measurement of anxiety, (16,18) and/ or adjustment of different confounding variables. (16)(17)(18) This does not fully explain the differences and it remains unclear why certain confounding variables in other studies, such as a tumour in the frontal lobe, (16)(17)(18) were not related to depression and/or anxiety in our study.…”

“…(15) Recently, three studies in the glioma population showed that LEV was associated with a higher risk of self-reported and clinician-diagnosed psychiatric adverse events, including anxiety. (16)(17)(18) Another commonly prescribed AED in the glioma population, valproic acid (VPA), (19) has been associated with decreased psychiatric and behavioural adverse effects in non-brain tumour-related epilepsy (BTRE) patients. (20) In addition, AEDs have been associated with objective as well as subjective cognitive impairment in both epilepsy (21) and glioma patients.…”

HLA-A*11:01 is associated with levetiracetam-induced psychiatric adverse events

“…In recent studies which investigated the possible associations among the location of brain lesion, the use of AEDs and the development of PAEs in patients with brain tumor-related epilepsy, frontal lobe tumors were highly associated with the development of PAEs after LEV treatment. [ 27 , 28 ] In addition, LEV-induced PAEs were more commonly reported in specific populations who had previous history of febrile convulsion or status epilepticus, previous history of psychiatric disorders, and familial history of psychiatric disorders. [ 7 , 29 ]…”

Brain Tumor Analysis Empowered with Deep Learning: A Review, Taxonomy, and Future Challenges

“…Tumor lesion location, use of Anti-Epileptic Drugs (AEDs) and the development of psychiatric symptoms have strong correlations among them. Treatment-Emergent Psychiatric Adverse Event (TE-PAEs) is possible through AED therapy and meets the conditions that includes onset within 4 weeks after AED therapy is perfromed, the absence of any other notorious possible concurrent cause, and disappearance upon drug discontinuation [146].…”