Assessment of psychiatric and behavioral adverse effects of antiepileptic drugs monotherapy: Could they have a neuroendocrine correlation in persons with epilepsy?

Objective: The study investigated overall adverse event (AE) burden and specifically psychiatric and behavioral side effects (PBAEs) in persons with epilepsy (PWE) on antiepileptic drugs (AEDs) monotherapy. It also assessed their correlation with neuroendocrine and oxidative stress biomarkers.

Methods: This cross-sectional observational study was conducted at a tertiary care hospital between 2016 and 2018. Persons with epilepsy above 18 years on monotherapy of levetiracetam (LEV) and conventional AEDs {carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA)} for at least 6 months were enrolled. Validated questionnaires, 'Mini-International Neuropsychiatric Interview (MINI 7.02)', 'Depression, Anxiety, and Stress Scale 21 (DASS-21)', 'Buss-Perry Aggression Questionnaire (BPAQ)', 'patient-weighted Quality of life Index in Epilepsy (QOLIE-10)', 'Pittsburgh Sleep Quality Index (PSQI)', and 'Liverpool Adverse Events Profile (LAEP)' were used to assess the PBAEs, quality of life, sleep quality, and AE profile. A subgroup of PWE recruited consecutively were considered for estimation of the following neuroendocrine biomarker levels: brain-derived neurotrophic factor (BDNF), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and total antioxidant capacity (TAC) which were then correlated with scores of above questionnaires.

Results: After screening 220 PWE, 163 PWE (58 on LEV and 105 on conventional AEDs) with a mean age of 29 ± 10 years were enrolled. Mini-International Neuropsychiatric Interview revealed that LEV group had higher association with PBAEs and lower quality of sleep compared to conventional AEDs (p = 0.032 and 0.046, respectively). Other scales did not show significant difference between LEV and conventional AEDs. In the subset of PWE (n = 74, 36 on LEV and 38 on conventional AEDs), LEV group had more association with the PBAEs (p = 0.010), higher physical aggression and anger components of BPAQ (p = 0.03 and 0.02, respectively), and more AE (p = 0.049) than conventional AED group. However, there was no significant difference in neuroendocrine biomarker levels.

Conclusion: Levetiracetam had a higher association with PBAEs and more AE when compared to conventional AEDs. There was no differential correlation of AEDs with the following neuroendocrine markers: BDNF, HVA, 5-HIAA, and TAC. These facts necessitate exploration of other mechanisms for LEV-induced PBAEs.