Multimodal rapid anti-depression: Esketamine combined with dexmedetomidine patient-controlled sleep for treatment-resistant depression - A retrospective study.
Journal of affective disorders – January 30, 2026
Source: PubMed
Summary
Nearly 60% of patients with treatment-resistant depression experienced sustained improvement for six months using a novel multimodal rapid anti-depression approach. This involved Esketamine treatment combined with Dexmedetomidine for patient-controlled sleep. Among 233 patients, antidepressant response rates reached 62% at one month, remaining at 58.49% by six months. Patient-controlled sleep was consistently linked to better outcomes. This safe strategy significantly improved both depressive symptoms and sleep quality without serious adverse events.
Abstract
To evaluate the efficacy and safety of a multimodal rapid anti-depression therapy that combines esketamine treatment with dexmedetomidine patient-controlled sleep (PCSL) in patients with treatment-resistant depression (TRD). We retrospectively included 233 patients with TRD who received the multimodal treatment. Baseline clinical characteristics were collected. Follow-up assessments were conducted at 1, 3, and 6 months after the first esketamine infusion. Depressive symptoms were assessed using the Hamilton Depression Scale (HAMD), and subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Esketamine administration during the initial course, additional esketamine treatment during follow-up, and PCSL use during follow-up were recorded. Adverse events were documented. HAMD and PSQI scores decreased significantly from baseline at 1, 3, and 6 months. Antidepressant response rates at these time points were 62.00%, 59.73%, and 58.49%, respectively. In multivariable analyses, PCSL use remained associated with response at 1, 3, and 6 months. Additional esketamine treatment during follow-up was associated with response at 3 months; at 6 months, the effect estimate remained favorable, although it did not reach statistical significance. Among other variables, age and disease duration were also associated with response. No serious adverse events were observed during follow-up. In this retrospective cohort, the multimodal treatment was associated with sustained improvements in depressive symptoms and sleep quality over 6 months, with an acceptable safety profile.