Epilepsy, anti‐epileptic medication use and risk of cancer

Abstract

Whether the powerful medications used to treat epilepsy increase the risk of cancer has been debated for decades, but until now no study could disentangle the contributions of anti-epileptic medications and epilepsy itself to cancer risk. Using a cohort comprising all Danish residents 16 years old at some point during the period 1996-2010 (>56 million person-years of follow-up) and information from national health registers, we examined associations between anti-epileptic medication use and cancer rates in persons with and without epilepsy, and between epilepsy and cancer rates in treated and untreated individuals. Associations were expressed as incidence rate ratios (IRRs) estimated using Poisson regression. Among persons without epilepsy, use of anti-epileptic medication increased the rates of most cancers little or not at all, although we observed moderately increased rates of liver, mouth and throat, and respiratory tract cancers (IRRs 1.40-1.59). In contrast, we observed strong associations between epilepsy and the rates of central nervous system and mouth and throat cancers (IRRs 2.00-3.91), and a modest association between epilepsy and the rate of respiratory tract cancers (IRRs 1.30-1.35), independent of anti-epileptic medication use. Our finding of only modest increases in cancer risk directly attributable to anti-epileptic medication use suggests that these medications may not be as strongly carcinogenic as has been feared, and that it is not primarily anti-epileptic medications that are responsible for the increased cancer risk among epileptics but another aspect of epilepsy diagnosis or treatment or an etiologic factor common to the two conditions.

Excess mortality and hospitalized morbidity in newly treated epilepsy patients

“…In another population-based study that utilized registers in Denmark and excluded people who developed cancer within a year of epilepsy diagnosis or initiation of AED therapy, use of AED increased the rates of most cancers little or not at all. 30 In contrast, epilepsy was associated with increased rates of CNS, mouth and throat, and respiratory tract cancers, independent of AED use. These findings raise the possibility of etiologic factors common to epilepsy and cancer.…”

Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study

“…Third, patients with an epilepsy diagnosis prior to the index date were excluded to investigate the potential confounding of other indications for anticonvulsants. 18 Combined therapies are common in bipolar disorder treatments. They are often used to discontinue or shift to another medication if the patient cannot tolerate the side-effects of the drug.…”

Association between antiepileptic drugs and hepatocellular carcinoma in patients with epilepsy: a population‐based case–control study

“…The risk of CNS cancers almost doubled (IRRs 3.91 vs. 2.00) in epilepsy patients treated with AEDs in comparison with that in epilepsy patients not treated with AEDs. They also found that, an increased risk of liver cancer is associated with epilepsy in people using AEDs (Kaae et al., ). A follow‐up study from Olsen et al., found that epilepsy patients were at significantly increased risks of brain and CNS (RR = 5.7) as well as lung (RR = 1.4) cancer.…”

“…The adjusted OR of patients with a last phenytoin use within 2 years prior to the index date was 1.92 (95% CI: 1.44–2.56). Research from Kaae, Carstensen, Wohlfahrt, Melbye, and Allison () also indicated a higher risk of cancer in the first year after the start of AEDs treatment.…”