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Multimodal rapid anti-depression: Esketamine combined with dexmedetomidine patient-controlled sleep for treatment-resistant depression - A retrospective study.

Yao-Zu Li, Cai-Qun Zhao, Mu-Yan Zuo, Ruo-Guo Wang, John P Williams, Jian-Xiong An

Journal of affective disorders January 30, 2026 DOI: 10.1016/j.jad.2026.121311 via PubMed

Summary

AI-generated from the abstract

A multimodal therapy combining esketamine with dexmedetomidine patient-controlled sleep (PCSL) was associated with sustained improvements in depressive symptoms and sleep quality over 6 months in 233 patients with treatment-resistant depression. Antidepressant response rates were 62% at 1 month, 59.73% at 3 months, and 58.49% at 6 months. Use of PCSL was linked to response at all time points, while additional esketamine during follow-up was associated with response at 3 months but not statistically significantly at 6 months. Age and disease duration also influenced response. No serious adverse events occurred.

Study at a glance

Characteristics Retrospective cohort Peer reviewed
Sample size 233
Population Patients with treatment-resistant depression
Interventions Esketamine Dexmedetomidine patient-controlled sleep
Duration 6-month follow-up
Topics Depression Esketamine
Keywords Dexmedetomidine Multimodal rapid anti-depression Patient-controlled sleep
Key finding Multimodal therapy combining esketamine and dexmedetomidine patient-controlled sleep was associated with sustained improvements in depressive symptoms and sleep quality over 6 months, with an acceptable safety profile.

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.

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