Abstracts

Falls resulting from imbalance account for significant morbidity and mortality in older adults and are a primary reason for nursing home admissions. Antiepileptic drugs (AEDs) are increasingly being prescribed for a variety of purposes. Despite their widespread use, little is known about the impact of the newer AEDs on balance and equilibrium. The objective of this study is to address the risk of imbalance from AED exposure. All double blind, placebo controlled clinical trials of AEDs submitted to the FDA for approval of the drug as adjunctive therapy in partial epilepsy were reviewed and pooled. Adverse events listed as either ataxia or unsteady gait were abstracted from the randomized controlled trials comparing the AED as adjunct therapy versus placebo for the following agents/ doses( in milligrams). Gabapentin 900-1800, Lamotrigine 300-500, Levetiracetam 1000-3000, Oxcarbazepine 600, 1200, 2400; Pregabalin 150, 600; Tiagabine 32-56; Topiramate 200-400, 600-1000 and Zonegran 100-200. Odds Ratios (OR) with 95% Confidence intervals (CI) were calculated for each agent/ dose versus placebo. Numbers needed to harm ( NNH) analysis was calculated with 95% CI. Reports of dizziness were not used in this analysis. Monotherapy and pediatric trials were excluded. 17 studies of AED versus placebo were included in the analysis representing 4209 individuals randomized to AED and 2576 on placebo. Pregabalin 150 and Tiagabine 32-56 were the only 2 agents to not have a significantly greater risk of imbalance compared to placebo. From the highest to the lowest risk of imbalance, the following is the OR, NNH of ataxia/ unsteady gait for each of the drug/ dose combinations as compared to its placebo control: Oxcarbazepine 2400 ( 13.24, 95% CI 6.32-27.75, NNH = 2, 95% CI 2-3), Oxcabazepine 1200 (5.01, 95% CI 2.56-9.79, NNH = 5, 95% CI 3-8), Lamotrigine 300-500 ( 4.53, 95% CI 3.21-6.41, NNH = 5, 95% CI 4- 7), Pregabalin 600 ( 6.6, 95% CI 2.86- 15.22, NNH = 6, 95% CI 4-9), Topiramate 200-400 ( 2.44, 95% CI 1.39- 4.26, NNH = 9, 95% CI 6-20), Topiramate 600-1000 ( 2.26, 95% CI 1.47- 3.47, NNH = 10, 95% CI 6-22), Gabapentin 900-1800 ( 2.56, 95% CI 1.61-4.08, NNH 13, 95% CI 8-26), Oxcarbazepine 600 ( 2.21, 95% CI 1.07-4.6, NNH = 13, 95% CI 7- 126), Zonegran 100-200 ( 7.21, 95% CI 1.78 -29.17, NNH = 20, 95% CI 12- 55), Tiagabine 32-56 ( 1.78, 95% CI 0.97- 3.24, ), Pregabalin 150 ( 1.79, 95% CI 0.72- 4.45) and Levetiracetam 1000-3000 ( 3.39, 95% CI 1.34- 8.59, NNH = 48, 95% CI 26-276). Although all of the AEDs reviewed can produce imbalance, Pregabalin 150, Tiagabine 32-56, and Levetiracteam 1000-3000 had the least risk for producing gait imbalance whereas Oxcarbazepine 1200, 2400, Lamotrigine 300-500, Pregabalin 600, and Topiramate 200-400 had the highest risk. Comparative research is needed to investigate how AEDs impact specific balance measures for better identification of patients at risk for this effect.