Objectives The Korean Medication Algorithm Project for Depressive Disorder 2025 (KMAP-DD 2025) was developed to provide updated, consensus-based pharmacological treatment guidelines for major depressive disorders in Korea, reflecting recent clinical evidence and domestic practice patterns. Methods The Korean Medication Algorithm Project for Depressive Disorder 2025 (KMAP-DD 2025) was developed to provide updated, consensus-based pharmacological treatment guidelines for major depressive disorders in Korea, reflecting recent clinical evidence and domestic practice patterns. Results For mild-to-moderate MDE, antidepressant (AD) monotherapy was recommended as the treatment of choice (TOC), with combination therapies involving mood stabilizers or atypical antipsychotics (AAP) as secondary options. In severe non-psychotic episodes, AD monotherapy, AD plus AAP, and dual AD therapy were all first-line options, while for severe psychotic episodes, AD plus AAP was the TOC. Escitalopram was consistently preferred as the first-line AD, and aripiprazole and quetiapine as leading AAPs. If initial treatments failed, strategies included switching or augmenting with another AD, AAP, or augmentation agents such as lithium, which remained the preferred third-line option. Conclusion Compared to the previous editions, KMAP-DD 2025 showed an increased preference for early combination therapies, especially in more severe or psychotic depression, and a higher reliance on AAPs. These recommendations reflect the evolving clinical trends and the need for practical, context-specific guidance in Korean practice.
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