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• Suboptimal medication self-management is common in epilepsy. • We show that the most common barriers to self-management are behaviorally mediated. • Negative medication beliefs and misconceptions about epilepsy were also prevalent. • Yet, only medication beliefs were associated with medication self-mismanagement. • Addressing medication beliefs may improve medication self-management in epilepsy. Suboptimal medication adherence is common in people with epilepsy (PWE) and disproportionally prevalent among racially/ethnically diverse patients. Understanding reasons and risks of suboptimal adherence is critical to developing interventions that reduce negative health outcomes. This cross-sectional study characterized common barriers to medication self-management, prevalence of negative medication beliefs, and gaps in epilepsy knowledge among predominantly African American and Caribbean American PWE and examined their interrelationships. Sixty-three PWE (Age = 42.1 ± 13.2; 60% female; 79% Black; 19% Hispanic/Latino) completed validated self-report questionnaires about medication self-management, medication beliefs, and epilepsy knowledge. Correlations and t-tests examined interrelationships. Four barriers to medication self-management were common, including not taking antiseizure medications at the same time every day, forgetting doses, not planning refills before running out, and spreading out doses when running low. More than half the sample believed medications were overused by prescribers. Nearly one-third believed medications were harmful, and nearly a quarter believed their antiseizure medications were minimally necessary with almost half reporting elevated concerns about negative consequences of antiseizure medications. Poorer medication self-management was associated with stronger beliefs that medications in general are harmful/overused by prescribers. Individuals who were "accepting" of their antiseizure medications (i.e., high perceived necessity, low concerns) were less likely to spread out time between doses when running low compared to non-accepting counterparts. Knowledge gaps related to the cause of seizures/epilepsy, chronicity of epilepsy treatment, and seizure semiology/diagnosis were common. Nevertheless, epilepsy knowledge was unrelated to medication self-management and medication beliefs. In these PWE, the most prevalent reasons for suboptimal medication self-management were behaviorally mediated and potentially modifiable. Negative medication beliefs and misconceptions about epilepsy and its treatment were common. Results further suggest that interventions addressing negative medication beliefs will be more effective than knowledge-based psychoeducation alone to improve medication self-management in this patient population. [ABSTRACT FROM AUTHOR]