Case report: Effectiveness of brexpiprazole and esketamine/ketamine combination: A novel therapeutic strategy in five cases of treatment-resistant depression

For patients with treatment-resistant depression who do not achieve functional recovery after multiple pharmacotherapies, combining brexpiprazole with esketamine or ketamine may offer a more rapid and effective augmentation strategy. This case series describes five complex cases of unipolar and bipolar treatment-resistant depression where conventional treatments failed to manage high-risk suicidal behavior or restore function. The authors discuss potential synergistic mechanisms of this novel combination, patient and clinical factors affecting response, challenges encountered, and implications for future practice and research.

Study at a glance

Abstract

A 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.