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Abstract Objective Observational studies have shown an association between COVID‐19 and epilepsy. However, causality remains unproven. This study aimed to investigate the causative effect of genetically predicted COVID‐19 phenotypes on epilepsy risk using a two‐sample Mendelian randomization (MR) analysis. Methods We retrieved summary‐level datasets for three COVID‐19 phenotypes (COVID‐19 susceptibility, COVID‐19 hospitalization, and COVID‐19 severity) and epilepsy from the genome‐wide association studies conducted by the COVID‐19 Host Genetics Initiative (COVID‐19 HGI) and International League Against Epilepsy (ILAE) consortium, respectively. To analyze the final results, nine MR analytic methods were utilized. The inverse‐variance weighted (IVW) method was chosen as the primary approach for data analysis to evaluate the potential causal effect. Other MR analytic methods (MR‐Egger regression, weighted median estimator, mode based‐estimator, and MR‐PRESSO) were used as a supplement to IVW to ensure the robustness of the results. Results The IVW approach demonstrated no causal association between any genetically predicted COVID‐19 phenotype and the risk of epilepsy [COVID‐19 susceptibility: odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.86–1.14, p = 0.92; COVID‐19 hospitalization: OR = 1.00, 95% CI = 0.96–1.04, p = 0.95; COVID‐19 severity: OR = 0.99, 95% CI = 0.96–1.01, p = 0.25]. Other MR complementary methods revealed consistent results. Additionally, no evidence for heterogeneity and horizontal pleiotropy was found. Significance This MR study revealed no genetically predicted causal relationship between COVID‐19 phenotypes and epilepsy.

Background: Epilepsy is one of the most common chronic brain diseases. Almost one-third of patients have drug-resistant epilepsy (DRE). Cannabidiol is being considered as a potential novel drug for treating DRE. Objectives: To investigate long-term efficacy and safety of cannabidiol in treatment of DRE and the differences in cannabidiol treatment among patients with different characteristics. Design: Systematic review and meta-analysis. Data sources and methods: Medline, Embase, and CENTRAL were searched for literature. RevMan5.4 was used for meta-analysis. The Intention-to-treat set and the random effect were used as the main analysis. Subgroup analyses were performed according to age, dose, concomitant antiseizure medications (ASMs), epilepsy syndromes, and study designs. Results: Fifty studies were included in this systematic review. A total of 4791 participants were collected. The responder rates (seizure frequency reduced at least 50%) at 12-, 24-, 48-, 72-, 96-, and 144-week were 0.40 [0.36, 0.45], 0.39 [0.34, 0.44], 0.37 [0.30, 0.44], 0.27 [0.17, 0.37], 0.22 [0.14, 0.30], and 0.38 [0.23, 0.53]. Seizure-free rates were 0.04 [0.03, 0.06], 0.04 [0.03, 0.05], 0.03 [0.02, 0.05], 0.03 [0.02, 0.03], 0.02 [0.01, 0.03], and 0.04 [0.01, 0.06]. Proportion of adverse events were 0.72 [0.61, 0.83], 0.62 [0.42, 0.81], 0.60 [0.41, 0.79], 0.35 [0.14, 0.56], 0.83 [0.75, 0.90], and 0.96 [0.94, 0.99]. The pooled 12-, 24-, 48-, 96-, and 144-week proportion of serious adverse events were 0.15 [0.09, 0.21], 0.23 [0.14, 0.31], 0.10 [0.06, 0.15], 0.31 [0.24, 0.38], and 0.40 [0.35, 0.45]. Subgroup analyses showed that there was no significant difference on efficacy and safety among age subgroups and epilepsy syndromes subgroups. For most periods, there were no significant difference on efficacy among subgroups of dose and concomitant ASMs. However, higher doses and more concomitant ASMs were associated with higher proportion of adverse events. Conclusion: Cannabidiol treatment of DRE has stable efficacy and fewer adverse events in early period. Long-term use may have decreased efficacy and increased adverse events. Dose escalation may not increase efficacy, but may increase adverse events. Furthermore, cannabidiol use may reduce dosage of other ASMs without reducing efficacy, thereby reducing adverse effects. Cannabidiol may have similar effects in various epilepsy syndromes. Trial registration: PROSPERO (CRD42022351250).

Epilepsy is a chronic neurological disorder associated with severe social and psychological effects, and most epilepsy patients often report at least one comorbidity. Accumulating evidence have suggested that lacosamide, a new generation of anti-seizure medications, may exhibit efficacy in the management of both epilepsy and its related comorbidities. Therefore, this narrative review aimed to elucidate the recent advancements regarding the therapeutic role of lacosamide in epilepsy-associated comorbidities. The possible pathophysiological mechanisms between epilepsy and epilepsy-associated comorbidities have been also partially described. Whether lacosamide improves cognitive and behavioral functions in patients with epilepsy has not been conclusively established. Some studies support that lacosamide may alleviate anxiety and depression in epilepsy patients. In addition, lacosamide has been found to be safe and effective in the treatment of epilepsy in people with intellectual disabilities, epilepsy of cerebrovascular etiology, and epilepsy associated with brain tumors. Moreover, lacosamide treatment has demonstrated fewer side effects on other systems. Hence, future larger and higher quality clinical studies are needed to further explore both the safety and efficacy of lacosamide in the treatment of epilepsy-associated comorbidities.