Paradoxical Depressive Response to Intranasal Esketamine in Treatment-Resistant Depression: A Case Series

A clinical case report documents two patients with treatment-resistant depression who initially responded to intranasal esketamine but subsequently experienced rapid deterioration in depressive symptoms and increased suicidal ideation, which improved upon discontinuation. The authors use validated psychiatric rating scales to assess outcomes and acknowledge that the mechanism underlying these paradoxical adverse reactions remains unclear.