Authors :
Presenting Author: Ali Rafati, MD, MPH – Johns Hopkins University
Yeganeh Pasebani, MD – Columbia University
Aditya Mittal, Student – Columbia University
Churl-Su Kwon, M.D., M.P.H., FRSPH. – Columbia University Irving Medical Center
Rationale:
Depression and epilepsy share a complex, bidirectional relationship. While it is well established that individuals with epilepsy often experience psychiatric comorbidities, less is known about whether depression itself predisposes individuals to develop epilepsy. Understanding this relationship is critical for improving early identification and intervention strategies. This systematic review and meta-analysis synthesize the best available evidence to quantify the incidence of epilepsy among individuals with and without depression.
Methods:
A comprehensive literature search was conducted across MEDLINE, Embase, and PsycINFO, last updated on March 9, 2025, following PRISMA guidelines. Eligible studies included prospective cohort and case-control studies that examined epilepsy incidence in individuals with and without depression. The primary outcome measure was the pooled hazard ratio (HR) for epilepsy among individuals with a history of depression. A secondary analysis examined the pooled odds ratio (OR) from case-control studies. Meta-analyses were performed using R (‘meta’ package).
Results:
From an initial 5781 records, 634 duplicates were removed. After screening 5147 studies, 5140 were excluded, leaving 7 studies for full-text review. One additional study was identified through hand-searching, bringing the total to 8 included studies.
The meta-analysis of two large cohort studies found a pooled hazard ratio of 2.39 (95% CI: 2.35–2.43, p< 0.001-Figure 1), suggesting a significant increase in epilepsy risk among individuals with prior depression, with low heterogeneity (I² = 0%). In contrast, a secondary analysis of four case-control studies assessing depression history in individuals with and without incident epilepsy produced a pooled odds ratio of 2.09 (95% CI: 0.92–4.76, p=0.08-Figure 2), showing a not statistically significant association with high heterogeneity (I² = 99%).
Conclusions:
Our findings strongly support that depression is associated with an increased risk of epilepsy, as demonstrated by the robust findings from large-scale population-based prospective cohort studies. Case-control studies are retrospective and may be more prone to recall and selection biases and issues with exposure misclassification, potentially weakening or obscuring the association. The underlying mechanisms remain to be fully elucidated but may involve shared neurobiological pathways, chronic stress responses, or inflammatory processes. Further research should investigate potential causal mechanisms and evaluate whether early identification and management of depression could reduce epilepsy risk. These findings underscore the importance of integrating psychiatric and neurological care to optimize patient outcomes.
Funding: None.