Inflammatory response to repeated subcutaneous esketamine in treatment-resistant depression: The role of baseline C-reactive protein.
Journal of Affective Disorders March 15, 2026 Patrícia Cavalcanti-Ribeiro, Lara Carvalho Araújo Melo De Souza, Vagner Deuel O de Tavares et al.
In a small open-label trial of 22 patients with treatment-resistant depression who received seven weekly subcutaneous doses of esketamine, those with elevated baseline C-reactive protein (CRP > 1 mg/L) showed significant reductions in CRP by week 4 and week 8, while patients without inflammation showed no change. By week 8, CRP levels in both groups were comparable. Although the inflammation group had a greater average reduction in depression severity (15.88 points on the MADRS scale versus 11.14 points), this difference was not statistically significant, and changes in CRP did not predict symptom improvement. Larger controlled studies are needed.