BACKGROUND: Major depressive disorder (MDD) is a growing global health concern, with its economic impact projected to reach USD 6.0 trillion by 2030. Treatment-resistant depression (TRD), characterized by non-responsiveness to initial treatments, adds a significant cost burden. In Malaysia, the National Health and Morbidity Survey 2023 reported a rising prevalence of depression in Malaysia, affecting approximately one million individuals. RESEARCH DESIGN AND METHODS: A combined retrospective chart review and cross-sectional survey was conducted at the Psychiatry and Mental Health Clinic of Hospital Kuala Lumpur (HKL) over an 18-month period, examining 286 patients diagnosed with MDD or TRD. Data were analyzed from governmental and societal perspectives, including direct medical costs, indirect costs, and other resource utilization. RESULTS: TRD patients exhibited significantly higher health-care utilization, including a fivefold increase in the likelihood of attending more than 10 consultations ( CONCLUSION: Early and effective management of MDD is essential to prevent progression to TRD, reducing healthcare resource utilization and costs. Adequate resource allocation for early intervention is critical to mitigate the economic impact of depression.