Abstracts

Rationale: Certain antiepileptic drugs (AEDs) have been implicated in immune system dysfunction; however, a systematic review of all AEDs has not yet been done. Postulated causes of the higher rate of infections in epileptics include both drug-dependent and independent factors (including T cell function, Ig levels, and HLA genes). This review of pivotal double blinded, placebo controlled trials was done to assess total incidence of infectious adverse effects (AEs) from AEDs used for epilepsy and for non-epilepsy indications.Methods: Package inserts of all current AEDs approved by the U.S. FDA for use in epilepsy were reviewed, and available data from placebo-controlled trials done for U.S. approval were pooled. For AEDs that are approved for other indications, data were recorded separately. Rates were compared using chi-square analyses. If analyses included expected values less than 5, Fisher exact tests were used.Results: Detailed AE data was unavailable for carbamazepine. Significantly higher rates of the following immune-related AEs were found in adult epilepsy patients using the specified AED versus placebo: rhinitis with lamotrigine (100/711 vs 38/419, p=0.013); infection (100/769 vs 36/439, p=0.011) and pharyngitis (51/829 v 18/499; p=0.043) with levetiracetam; infections with sodium valproate (35/208 vs 4/70, p=0.021); and urinary tract infection (UTI) with vigabatrin (7/177 vs 0/135, p=0.019). Infection was more common in adults with herpetic neuralgia treated with pregabalin (60/852 vs 16/398, p=0.037). However, no such increase was found in adult epilepsy trials. There was a trend towards greater occurrence of pharyngitis (26/597 vs 6/291, p=0.085) and UTI (17/597 vs 3/291, p=0.087) with topiramate and pharyngitis with tiagabine (46/639 vs 16/366, p=0.073) in adults with epilepsy. In adults with neuropathic pain, there was a trend towards higher rates of conjunctivitis with gabapentin (4/336 vs 0/227, p=0.099). Among pediatric epilepsy cohorts, gabapentin was associated with higher rates of fever (12/119 vs 4/128, p=0.026) and viral infection (13/119 vs 4/128, p=0.016); and lamotrigine of UTI (5/168 vs 0/171, p=0.023). Rates of pharyngitis with levetiracetam trended towards being significantly greater in patients aged four and older with primary generalized tonic-clonic seizures (11/79 vs 4/84, p=0.080). Incidence of immune-related side effects was not significantly different from placebo in those taking felbamate, oxcarbazepine, rufinamide, or zonisamide. We could not find any instance where infection was significantly greater in the placebo group than an AED group.Conclusions: The results of these clinical trials suggest that many AEDs with a variety of mechanisms are associated with increased infections, mostly minor. The reason for this effect and the relation between the immune effect and seizure control warrant further investigation.