Abstracts

Rationale: AEDs have unique pharmacokinetic & pharmacodynamic properties which contribute to their efficacy. These same properties also contribute to a wide variety of adverse drug reactions (ADRs) which impact safety & ultimately effectiveness. In recent trials, the efficacy of AEDs has been demonstrated by ≥ 50% reduction in seizures (Loscher 2011). However, the reported incidence of patients experiencing at least 1 ADR due to an AED is up to 88% and this undermines the true effectiveness of AEDs (Perucca 2009). Furthermore, it is known that the likelihood for effective seizure control is compromised when patients fail their first AED, whether it be due to lack of efficacy / ADRs (Brodie 2011). Here we have identified patients with epilepsy who experienced AED ADRs to demonstrate AED efficacy versus AED effectiveness. Methods: Seven patients with epilepsy who experienced AED ADRs were reviewed. ADRs were categorized into 5 domains: cognition, neuropsychological, changes in physiological parameters, metabolic effects, & gait/coordination. Efficacy & safety outcomes are reviewed and discussed. Results: Case 1: A 38 year-old man developed paresthesias on topiramate (TPM) and was subsequently switched to phenytoin (DPH). While on DPH, he developed disequilibrium, memory difficulties, and gingival hypertrophy resulting in loss of teeth. He went through multiple AED trials before undergoing a VNS implantation. Case 2: A 44 year-old man developed paranoid delusions after 3 years of levetiracetam (LVT) therapy. The paranoid delusions resolved upon LVT discontinuation; however, he developed a new seizure semiology after discontinuation. Case 3: A 67 year-old male developed hyponatremia after 20 years of carbamazepine (CBZ) therapy. His hyponatremia resulted in a hospital admission and dose reduction of his AEDs. Case 4: A 54 year-old man experienced hyponatremia upon initiation of oxcarbazepine (OXC). He was asymptomatic and chose to continue on OXC to maintain seizure control. Case 5: A 59 year-old man was started on valproic acid (VPA) and gained over 20 pounds in 7 months. Alternative pharmacotherapies suitable for his form of genetic epilepsy were unavailable and he remained on VPA. Case 6: A 64 year-old man who had been seizure free for over 30 years on CBZ demonstrated signs of osteoporosis. He continued on therapy despite clear signs of osteoporosis. Case 7: A 65 year-old man developed intolerable gait instability resulting in multiple falls after the addition of lamotrigine (LTG) to a regimen consisting of VPA, LVT & TPM. Conclusions: All 7 patients experienced ADRs that can be attributed to their AED therapy. Three patients remained on therapy in order to maintain seizure control, one patient discontinued therapy resulting in worsening seizures, and three patients discontinued or switched therapy. Given the high incidence of ADRs and its' negative impact on seizure control, it is essential to consider not only the efficacy of AEDs when designing a therapeutic regimen but also its' safety and overall effectiveness.