Abstracts

Rationale: The side effects of Levetiracetam (LEV) are still under review and prevention of severe adverse drug reactions (ADRs) is essential for appropriate treatment of epilepsy. This study reviews acute psychiatric adverse events (PAEs) in children on LEV. A description of the cases, predisposing factors and common associations will be highlighted. Suggestions for prevention of PAEs will be discussed. Methods: Out of 207 patients registered as taking LEV at BC Children’s Hospital eight were identified by neurologists as developing acute PAEs. Medical records were retrospectively reviewed and clinical data extracted for analysis. Descriptive analysis was performed including mean and associated 95% confidence intervals (CI). Results: The prevalence of PAEs is 2.4% (8/207). Demographic data show 75% (6/8) females, 25% (2/8) males, and average age 167 months (95%CI 104, 228). Past history revealed developmental delay 25.0% (2/8), learning disability 62.5% (5/8), behavioral issues 37.5% (3/8), psychiatric history 62.5% (5/8), family psychiatric history 28.6% (2/7), febrile seizures 12.5% (1/8), and abnormal MRI 62.5% (5/8). LEV was started after failing an average of 5.4 (95%CI 3.2, 7.6) anti epileptic drugs (AEDs). All patients (100.0%, 8/8) were on two or more AEDs with LEV. The mean starting dose of LEV was 7.37 mg/kg/d (95%CI 3.18, 11.55) with titration at 250mg/week-2 weeks. The mean dose when PAEs appeared was 31.47 mg/kg/d (95%CI 6.23, 56.71). The mean number of days until onset of PAEs was 155 (95%CI 15, 294). PAEs included aggression/agitation 87.5% (7/8), behavioral changes 87.5% (7/8), mood changes 50.0% (4/8), hallucinations 37.5% (3/8), suicidal ideation 25.0% (2/8), paranoia 25.0% (2/8), and sleep disturbance 25.0% (2/8). All eight patients returned to baseline after a mean of 45 days (95%CI -0.71, 90), with resolution of the PAE upon cessation (75.0%, 6/8) or decreased dose (25.0%, 2/8) of LEV. Conclusions: Findings are consistent with the literature and suggest that serious PAEs, such as suicidal ideation, exist in pediatric patients on LEV. Despite poly therapy when starting LEV, once on LEV the PAEs appeared, and upon removal of LEV the PAEs resolved. This provides support for a causal association. There may be a threshold dosage in which patients predisposed to PAEs will manifest symptoms. This was evident in two patients who returned to baseline after decreasing the dosage of LEV. The prevalence of PAEs is lower than other studies report which may be due to small sample size, unidentified cases, and cessation of therapy prior to PAEs manifested. Risk factors for PAEs reported in the literature and present in this study include abnormal MRI, learning and developmental disability, behavioral issues, past psychiatric history, family psychiatric history and history of febrile seizures. Prior to commencing LEV it is important to assess known reported risk factors for PAEs. Ensure close monitoring of patients on LEV thereby leading to prevention, early diagnosis, and appropriate management of PAEs.