Lai Fong ChanLuke Sy-Cherng WoonNuur Asyikin Mohd ShukorChoon Leng EuNurazah IsmailSong Jie ChinNik Ruzyanei Nik JaafarAzlin Baharudin2024-05-282024-05-2820222022-7-27Chan LF, Woon LS-C, Mohd Shukor NA, Eu CL, Ismail N, Chin SJ, Nik Jaafar NR and Baharudin A (2022) Case report: Effectiveness of brexpiprazole and esketamine/ketamine combination: A novel therapeutic strategy in five cases of treatment-resistant depression. Front. Psychiatry 13:890099. doi: 10.3389/fpsyt.2022.8900991664-06401961-310.3389/fpsyt.2022.890099https://www.frontiersin.org/articles/10.3389/fpsyt.2022.890099/fullhttps://oarep.usim.edu.my/handle/123456789/6897Front. Psychiatry, 22 July 2022 Sec. PsychopharmacologyA significant proportion of patients with treatment-resistant depression do not attain functional recovery despite administration of multiple steps of pharmacotherapeutic strategies. This highlights the elusiveness of meeting unmet needs in existing pharmacotherapies for treatment-resistant depression. There is accumulating evidence that antidepressant agents involving the glutamatergic system such as brexpiprazole and esketamine/ketamine have more rapid onset of action and potentially improved effectiveness as an augmentation therapy in treatment-resistant depression. This case series aimed to report five complex cases of unipolar and bipolar treatment-resistant depression where conventional treatment strategies were inadequate in managing high risk suicidal behavior and achieving functional recovery. We discussed further the possible synergistic mechanisms of the novel combination strategy of brexpiprazole and esketamine/ketamine, clinical and patient factors that influenced treatment response, challenges with this combination strategy and implications for future practice and research.entreatment-resistant depression, effectiveness, ketamine, brexpiprazole, esketamineArticle11013890099