A Meta-Analysis of Multimodal Non-Drug Interventions for Depression in Adults

Background: Depression affects over 264 million people globally and is projected to become the leading cause of disease burden by 2030. While pharmacotherapy remains a cornerstone of treatment, limitations including side effects, adherence issues, and treatment resistance necessitate exploration of alternative therapies. Multimodal non-pharmacological interventions encompassing psychological, behavioral, and lifestyle approaches—are increasingly recognized as valuable components of depression care. Objectives: This meta-analysis evaluated the effectiveness of non-drug interventions, including exercise therapy, cognitive behavioral therapy (CBT), nature-assisted therapy, and psychosocial rehabilitation, in reducing depressive symptoms among adults. Methods: Following PRISMA 2020 guidelines, a systematic search of six databases identified randomized controlled trials and controlled cohort studies published between 2013 and 2024. Studies included adult participants diagnosed with depression and compared structured non-pharmacological interventions to treatment-as-usual or minimal intervention. Standardized mean differences (SMD) were calculated using a random-effects model. Results: Five studies met inclusion criteria (N = 965). The pooled SMD was –0.27 (95% CI: –0.40 to –0.14), indicating a small-to-moderate but statistically significant effect favoring intervention groups. Exercise-based therapies showed the strongest and most consistent effects (SMD = –0.39), followed by psychosocial rehabilitation (–0.25), nature-assisted therapy (–0.20), and digital CBT (–0.10). Heterogeneity was moderate (I² = 48.1%), and no significant publication bias was detected. Conclusion: Non-pharmacological interventions can effectively reduce depressive symptoms, particularly when exercise is incorporated. These therapies offer viable alternatives or complements to medication, supporting holistic and patient-centered approaches in psychiatric rehabilitation. Further research should explore long-term outcomes and optimize intervention integration in diverse healthcare settings