Esketamine Use and Postoperative Mental Health in Elderly Chinese Patients

High Prevalence of Postoperative Anxiety and Depression in Elderly Chinese Patients

A multicenter observational study published on October 24, 2026, in OpenAlex (source) reports that more than one in five elderly Chinese patients experience significant anxiety or depression symptoms following non-cardiac surgery. The research included 7,568 patients aged 65 and above, with a median age of 71, across multiple hospitals in China between April 2020 and April 2022. Using validated screening tools—the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9)—the study found 22.1% had anxiety and 23.6% had depression symptoms postoperatively. These rates are notably higher than previously reported in similar populations, suggesting a substantial and underrecognized mental health burden in the perioperative period for elderly patients in China.

Esketamine and Other Factors Linked to Lower Symptom Rates

Intraoperative administration of esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist with pharmacological similarities to both anesthetics and psychedelic agents, was independently associated with lower odds of postoperative anxiety and depression. The study also identified intraoperative dexmedetomidine and male sex as protective factors, while a history of malignant tumor and preoperative sleep disorder increased risk. The association between esketamine and reduced psychiatric symptoms is particularly noteworthy, as esketamine is approved for treatment-resistant depression in several jurisdictions and is being studied for rapid-acting antidepressant effects. This finding, while observational, suggests a possible perioperative mental health benefit that warrants further investigation in randomized controlled trials (RCTs).

Clinical and Policy Implications for Perioperative Mental Health

The high prevalence of postoperative anxiety and depression in elderly Chinese patients underscores a significant unmet need for perioperative mental health interventions. Currently, routine screening and proactive management of psychiatric symptoms are not standard practice in many surgical settings in China or globally. The potential role of esketamine, as suggested by this study, could inform future clinical trial designs targeting perioperative mental health, especially in populations at elevated risk due to age, comorbidities, or surgical complexity. Furthermore, these findings may prompt policymakers and hospital administrators to consider integrating mental health assessments into perioperative care protocols, particularly for elderly patients.

Importantly, the study also found that postoperative anxiety was associated with higher odds of infectious complications and acute pain, while depression was linked to delirium and acute pain. These associations highlight the broader clinical impact of untreated psychiatric symptoms, affecting not only quality of life but also recovery trajectories and healthcare resource utilization.

Risks, Limitations, and Unknowns

While the association between intraoperative esketamine and reduced psychiatric symptoms is compelling, the study's observational design limits causal inference. Confounding factors—such as surgical indication, anesthetic regimen, and patient selection—may influence both the use of esketamine and mental health outcomes. Additionally, the safety profile of esketamine in elderly surgical patients, particularly with respect to cardiovascular and neuropsychiatric side effects, remains incompletely characterized in this context. The study did not report on dosing, timing, or the potential for adverse events related to esketamine use.

Another limitation is the lack of longitudinal follow-up, leaving the duration and clinical significance of these psychiatric symptoms unclear. Cultural factors, stigma, and variability in mental health reporting may also affect prevalence estimates and generalizability to other populations. Notably, this study did not include a psychedelic intervention or assess psychedelic experiences, but rather focused on a pharmacologically adjacent agent.

Future Directions for Research and Practice

Future research should prioritize randomized controlled trials to evaluate the efficacy and safety of esketamine and related agents for perioperative mental health in elderly populations. Such studies should include detailed monitoring of adverse events, functional outcomes, and long-term psychiatric trajectories. There is also a need for implementation research to identify scalable, culturally appropriate mental health screening and intervention strategies in perioperative care.

For stakeholders in psychedelic and ketamine research, this study provides a concrete example of a large, real-world population with high unmet need and initial signals of benefit from NMDA antagonists. Integrating mental health outcomes into surgical care pathways could represent a new frontier for both clinical innovation and health policy, particularly in rapidly aging societies.

Byline: Dr. Alex Chen, MD, MPH. Reviewed by Dr. Lin Wang, PhD, on 2026-10-28. Research based on primary publication in OpenAlex and direct review of study methods and results.