PhD Student University of Florida Gainesville, United States
Background: Topiramate is utilized for various medical conditions. Risk mitigation strategies to prevent prenatal exposure due to its potential teratogenic effect need to consider condition-specific risk-benefit, but it is unclear how prenatal exposure varies across conditions.
Objectives: We aimed to compare prenatal exposure rates and contraceptive use among topiramate initiators across approved or off-label indications (epilepsy, migraine, chronic pain, obesity, bipolar disorder).
Methods: This retrospective cohort study used MerativeTM Marketscan® Research databases from 2011-2019. We included the first available episode of female patients aged 14-53, newly initiating single-agent topiramate products with no documented history of infertility within 6 months of prior enrollment. Participants were followed until infertility diagnosis, estimated conception, disenrollment, end of study, or end of treatment. Treatment ended at exhaustion of dispensed days’ supply and absence of a new topiramate dispensing claim within 14 days. Exposure periods ended earlier if ≤45 weeks enrollment was available thereafter to ensure capture of pregnancy. To assign indications we prioritized diagnoses immediately preceding treatment initiation. We calculated crude and age-standardized (to 2015 US Census data) prenatal exposure rates to topiramate by indications. We also estimated hormonal contraceptive use during topiramate treatment episodes (pills, vaginal rings, patches, injectables, intrauterine devices including copper, and implants).
Results: We identified 108,672 women who newly initiated topiramate. Among those, there were 55.1% with chronic pain, 26.7% with migraine, 10.3% with obesity/overweight, 5.9% with bipolar disorder, and 2.1% with epilepsy. Contraceptive use was highest among women with migraine (29% with ≥1 day of contraceptive use) and lowest among those with chronic pain (20%). Topiramate users with epilepsy had the highest crude rate of prenatal exposure (2.36 per 100 person-years, 95%CI: 1.54-3.62), and those with chronic pain had the lowest (1.11, 95% CI: 0.96-1.28). After age standardization, we observed the highest rate of prenatal topiramate exposure in patients with epilepsy (2.69, 95%CI: 1.61-4.09) and the lowest in those with bipolar disorder (1.65, 95%CI: 1.07-2.36).
Conclusions: Less than one-third of topiramate users had concomitant contraceptive use. The rate of conception during topiramate use varied across indications. While use during pregnancy might have been intended in some cases (e.g., weighing risk-benefit for seizure control), enhanced patient counseling and risk mitigation for other potential uses (e.g., obesity) might be needed.
