Long-Term Medication-Induced Weight Change Across Common Antiseizure Medications: A Target Trial Emulation Study

To estimate long-term weight change after initiation and adherence to commonly used antiseizure medications (ASMs) and examine differences in weight change across ASMs compared to topiramate.

We included 52,309 adult patients who initiated ASMs, applied a target trial emulation approach to control time-varying confounding and selection bias, and examined the long-term comparative effects on weight change after initiating and adhering to different ASMs at 6 and 12 months post initiation.

The most commonly initiated ASM was topiramate (41.2%). In comparison to topiramate, we estimated higher 6-month weight change under initiation and adherence to levetiracetam 0.94 kg (95% CI 0.20, 1.64), lamotrigine 1.44 kg (0.74, 1.99), valproate 2.42 kg (1.71, 2.88), carbamazepine 1.32 kg (0.46, 2.16), and oxcarbazepine 1.74 kg (0.85, 2.71), with similar results at 12 months and in sensitivity and subgroup analyses. These results were driven mostly by weight loss with use of topiramate rather than weight gain with use of other ASMs. Results were similar though attenuated when accounting for medication initiation only.

Topiramate was associated with weight loss at 6 and 12 months under either initiation and subsequent adherence or initiation-only effects; other medications were associated with higher weight change. These results provided important information to help with decision-making regarding ASM initiation.