Distinct therapeutic profiles of ketamine in treatment-resistant depression: an exploratory analysis.
The international journal of neuropsychopharmacology May 3, 2026 Kuan-I Liu, Wei-Chen Lin, Cheng-Ta Li et al.
Intravenous ketamine rapidly reduces depressive symptoms in treatment-resistant depression, but its effects vary by symptom. In a pooled analysis of two randomized controlled trials involving 154 adults, ketamine significantly improved total depression scores and seven individual symptoms, including suicidal thoughts. However, the degree of treatment resistance, measured by the Maudsley Staging Method, moderated improvements in apparent sadness and inner tension: patients with higher resistance showed less benefit. In contrast, the anti-suicidal effect of ketamine remained robust regardless of resistance severity. These exploratory findings suggest that symptom-specific treatment strategies may be needed, with ketamine potentially serving as an acute intervention for suicidal crises across resistance levels, while highly refractory patients may require augmentation for certain affective symptoms.