Efficacy of psychological and behavioral interventions for depressive symptoms in people with epilepsy: a systematic review and meta-analysis.

Background: Depression is a common and clinically important comorbidity in people with epilepsy and is associated with poorer quality of life, impaired treatment adherence, increased disease burden, and worse clinical outcomes. Psychological and behavioral interventions have been increasingly applied in this population; however, the overall efficacy and consistency of evidence across different intervention categories remain uncertain. Objective: This systematic review and meta-analysis aimed to evaluate the effects of psychological and behavioral interventions on depressive symptoms in people with epilepsy, with particular attention to cognitive behavioral therapy, mindfulness-based interventions, self-management or collaborative-care programs, and relaxation-based interventions. Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library for studies published between January 2005 and May 2026. Randomized controlled trials and controlled clinical studies evaluating eligible interventions for depression-related outcomes in people with epilepsy were included. The primary outcome was depression severity measured using validated rating scales. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for continuous outcomes. Random-effects models were used to account for clinical and methodological heterogeneity. Risk of bias and certainty of evidence were assessed using the Cochrane RoB 2 tool and the GRADE framework, respectively. Results: Twenty-two studies were included in the systematic review, of which 11 contributed data to the quantitative synthesis of continuous depression severity outcomes. Overall, active psychological and behavioral interventions were associated with significantly greater reductions in depressive symptoms compared with treatment as usual or control conditions (SMD = -0.63, 95% CI: -0.90 to -0.36). In subgroup analyses, cognitive behavioral therapy showed a significant beneficial effect (SMD = -0.55, 95% CI: -0.90 to -0.21), as did mindfulness-based interventions (SMD = -0.46, 95% CI: -0.86 to -0.07) and self-management or collaborative-care interventions (SMD = -0.43, 95% CI: -0.74 to -0.12). Progressive muscle relaxation showed a large effect in a single small study (SMD = -1.65), but this finding should be interpreted cautiously because of limited evidence. Most studies were judged as having some concerns regarding risk of bias, mainly due to lack of blinding, reliance on self-reported outcomes, and incomplete outcome reporting. The certainty of evidence ranged from low to very low across intervention categories. Conclusion: Psychological and behavioral interventions may help reduce depressive symptoms in people with epilepsy. Among the available intervention categories, cognitive behavioral therapy and self-management or collaborative-care interventions showed the most consistent and clinically interpretable evidence. Mindfulness-based interventions may also be beneficial, although the overall certainty of evidence remained low. Findings for progressive muscle relaxation remain preliminary. Further well-designed, adequately powered randomized trials with standardized outcome measures and longer follow-up are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261403546, PROSPERO CRD420261403546.