Treatment with carbamazepine and lamotrigine was associated with an increased risk for squamous cell carcinoma (SCC), according to study results published in the Journal of the American Academy of Dermatology.

Danish prescription and statistics registers were retrospectively examined to identify skin cancer cases occurring between 2004 and 2015. Cancer cases included basal cell carcinoma (BCC), SCC, and malignant melanoma (MM) and antiepileptic drug (AED) utilization rates were compared with disease-free controls. Only AEDs (carbamazepine, clonazepam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, and valproic acid) that were used regularly for ≥1 year were included in the study. Odds ratios (ORs) for skin cancer associated with high cumulative use of AEDs (≥500 daily doses) were estimated and compared with non-use.

The majority of AEDs included in the study held a neutral association with skin cancer. The researchers wrote that because AEDs and other photosensitizing drugs are hypothesized to increase skin cancer risk by increasing sensitivity to UV radiation, it was expected that the biggest increase in risk would be for SCC. They found that the only AEDs associated with SCC were carbamazepine (odds ratio [OR], 1.88; 95% CI, 1.42-2.49) and lamotrigine (OR, 1.57; 95% CI ,1.12-2.22). For each 500 defined daily dose increase in cumulated dose in carbamazepine, the OR increased by 1.07 (95% CI, 1.01-1.13). Comparatively, the corresponding OR for lamotrigine was 0.96 (95% CI, 0.88-1.06). Estimated absolute risks were low. The researchers estimated that a total of 6335 person-years spent with high cumulative carbamazepine exposure would be necessary for 1 SCC.

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Study limitations include the retrospective design, as well as the lack of risk factors for skin cancer such as sun exposure.

Despite their findings, the researchers wrote that “the evaluation of a potentially increased risk of skin cancer needs to be weighed against the established benefits of AED therapy.”

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Reference

Kristensen KB, Pedersen SA, Johannesdottir Schmidt SA, Pottegård A.  Use of antiepileptic drugs and risk of skin cancer: A nationwide case-control study [published online May 28, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.05.055