Risk factors of psychiatric comorbidities among drug-resistant epilepsy patients: a network meta-analysis

Abstract

Drug-resistant epilepsy (DRE) is defined by International League Against Epilepsy (ILAE) as continued occurrence or persistence of seizures despite treatment with at least two syndrome-adapted antiseizure drugs (ASD) used at an adequate daily dose. This study aims to perform a network meta-analysis to identify and compare the relative contribution of various risk factors to psychiatric comorbidities among patients with DRE. This is a network meta-analysis study using 6 databases for searching the articles with certain PICO criterias. The risk of bias was assessed using ROBINS-E. The final results were analyzed using SUCRA analysis to rank the risk factors’ list. Four included studies were retrospective cohort and cross-sectional, with sample sizes ranging from 50 to 272 participants. Among the evaluated factors, “Onset age < 18 years” demonstrated the highest OR at 1.81 [95% CI 0.29 to 11.30, p = 0.525], suggesting a potential—though non-significant—association with increased depression risk. This risk had the highest SUCRA value at 0.7329. “Secondary” demonstrated the highest OR at 1.14 [95% CI 0.66 to 1.98, p = 0.640] and had the highest SUCRA value at 0.7177. These criterias are closely linked to the psychiatric comorbidities with depression and anxiety, respectively. For depressive outcomes, an earlier age of epilepsy onset (< 18 years) and a right-sided epileptogenic focus consistently emerged as the highest-ranked potential risk indicators, while focal onset and idiopathic etiologies exhibited subtle, descriptive protective trends. Conversely, for anxiety outcomes, a secondary epilepsy etiology and limbic system structural involvement demonstrated a stronger probability of being linked to increased symptom burden, whereas temporal and focal onsets trended toward a lower risk profile.