The SAFE-study: comparative treatment effect, side effect and health evaluation of allopathic versus ayurvedic treatments for major depressive disorder: a naturalistic real-world study

Background: Major Depressive Disorder (MDD) is a prevalent mental health condition with diverse treatment modalities. There is an unmet need in the treatment of major psychiatric disorders such as depression and naturalistic treatment options which are desirable particularly for chronic and severe courses of mental illness. In addition, there is an evidence gap for naturalistic treatment options for depression. This study compares the treatment effects and side effects of allopathic and ayurvedic treatments for MDD within a real-world setting. Allopathic approaches typically involve antidepressants and psychotherapy, while ayurvedic treatments may encompass herbal remedies, panchakarma, manual therapies, dietary modifications, yoga, meditation and lifestyle interventions. Methods: This six-month, naturalistic observational study will involve 105 adult participants (18-65 years) diagnosed with MDD according to DSM-5 criteria. Participants will be categorized to one of three groups: allopathic-only treatment (n=35), ayurvedic-only treatment (n=35), or a combination of both (n=35). Depressive symptom severity will be assessed as primary endpoint using primarily the MDRS, and secondarily HAMD and PHQ-9 scales at baseline, every 2 weeks until week 8, followed by monthly assessments until months 6. Secondary outcomes will exploratively include side effects (UKU, GASE, MARS), quality of life and daily functioning (WHOQoL-BREF, GAF, FAST) as well as general health measures (e.g. lab tests). Results: The study will compare changes in primary and secondary outcome measures across the three treatment groups over time (baseline vs. week 8, month 3 and month 6) using appropriate statistical models for longitudinal data (e.g., repeated measures ANOVA, mixed-effects models. Conclusions: This study will provide valuable real-world evidence on the comparative treatment effects and side effects of allopathic and ayurvedic treatments for MDD, informing clinical practice and future research directions in this area. Findings will contribute to a more nuanced understanding of treatment options for individuals with MDD.