Psychiatric Adverse Effects of Levetiracetam in Malignant Glioma Populations; a Retrospective Cohort Study

Abstract

Objective: Levetiracetam is commonly used in malignant glioma populations because of its efficacy, limited drug-drug interactions and adverse effects. Although, there has been growing evidence of adverse neuropsychiatric side effects from levetiracetam; however, such evidence in malignant brain tumor settings is limited. Hence, we hypothesized that malignant glioma patients exposed to levetiracetam would also experience more adverse neuropsychiatric effects compared to patients not receiving this medication.Material and Methods: A retrospective cohort analysis was conducted in 150 high grade malignant glioma patients at our Cleveland Clinic Cancer Center; from 2013-2014, comparing the accumulative adverse neuropsychiatric outcomes between patients who received levetiracetam and patients who did not (n=108 and 42, respectively). A sub-analysis of each specific neuropsychiatric side effect between these two groups was performed.Results: Patients with malignant glioma receiving levetiracetam had increased risk of developing neuropsychiatric adverse effects compared to the non-levetiracetam group (odds ratio=2.08, p-value=0.040, 95% confidence interval=1.00-4.36). After adjusting for confounding factors, past psychiatric history and the interaction between seizure and levetiracetam use was significantly associated with neuropsychiatric problems. Delirium, psychosis, and irritability were more common in the levetiracetam group, and likely led to more psychiatric referrals, starting of psychotropic medications, and vitamin B6 use.Conclusion: Incidence of neuropsychiatric presentations in malignant glioma patients was higher in the levetiracetam exposed group than the non-exposed group. The changes, or emergence of new neuropsychiatric behaviors should prompt clinicians to search for possible causes; including levetiracetam adverse effects, so they can be managed accordingly.