Abstracts

Rationale: The objective of the study was to compare the psychiatric and behavioral side effect (PBSE) profiles of both older and newer antiepileptic drugs (AEDs) in children and adolescent patients with epilepsy.Methods: As part of the Yale and Columbia AED Database Project, we reviewed patient background, medical history, AED use, efficacy, side effects, and dose and medication changes for patients newly started on an AED (children: <12 years; adolescents: >12 and <18 years). We first used univariate logistic regression analyses to test the correlation between 80 non-AED/patient related potential predictor variables and the rate of PBSE. Variables that were significant in the univariate analysis (P<0.05) were then entered into a multivariate logistic regression analysis where the significance level was adjusted using the Bonferroni method. Psychiatric side effects included in this study were depressive mood, psychosis, anxiety, and suicidal ideation. Behavioral side effects included in this study were irritability, aggression, tantrum/outbursts, and other behavioral. Finally, we compared the overall rate of intolerable PBSEs (IPBSEs) (i.e. PBSEs that led to AED dosage reduction or discontinuation) attributed to a particular AED by physician-confirmed patient report. Significance levels for predictor analysis and AED PBSE profile analyses were set to P=0.05/number of comparisons. P-values between 0.05 and significance were considered trends.Results: 922 patients met our inclusion criteria. Average age was 12.1±5.2 years. PBSEs and IPBSEs occurred in 13.8% and 11.2% of patients, respectively; 5.3% of IPBSEs were resolved with dose decrease, while 5.9% were resolved by AED cessation. Overall, history of psychiatric condition, absence seizures, and failing 2 or more AEDs were significantly associated with increased PBSE rates (P<0.001; see Table 1). Diagnosis of frontal lobe epilepsy trended towards an association with increased PBSE rates (P=0.038). Levetiracetam (LEV) had the greatest PBSE rate (16.2%). This was statistically significant when compared to the rate with all other AEDs combined (5.2% PBSE; P<0.001). LEV was also significantly associated with high IPBSE (14.0%, P<0.001), high dose decrease rate (7.1%, P<0.001), and trended towards a high complete cessation rate (6.8%, P=0.043) compared to all other AEDs combined (3.7% IBSE, 1.7% dose decrease, and 2.1% cessation). Zonisamide (ZNS) led to significantly higher cessation rate due to IPBSE (6.7%) compared to all other AEDs combined (2.4%; P<0.001). Lamotrigine trended towards lower PBSE (3.0%, P=0.004) and IPBSE rates (2.5%, P=0.030) when compared to all other AEDs combined (7.4% PBSE and 5.6% IBSE).Conclusions: PBSEs related to AEDs are most common in adolescents and children with a prior psychiatric history, absence seizures, intractable epilepsy, or possibly frontal lobe onset seizures. PBSEs appear to occur more frequently in adolescents and children taking LEV compared to other AEDs, followed by those taking ZNS. Our findings may have practical implications in clinical practice and help facilitate the AED selection process.