Non-Pharmacological Effects of Ketamine for Depressed Patients in the Perioperative Period

Major Depressive Disorder (MDD) is a severe mental illness, ranking in the top contributors to global disease burden. Moreover, during a perioperative period, a diagnosis of MDD increases risk of negative surgical outcomes. While several trials have explored the hallucinogen ketamine for its antidepressant effects, there is limited research into its efficacy when administered during general anesthesia. Our subsequent randomized controlled trial indicates that postoperative mood is influenced not only by ketamine infusion, but rather strongly by expectancy bias, quality of recovery, and other non-pharmacological effects. We employed a dataset of similar surgical patients not enrolled in any trials to investigate expectancy and examine whether current measurement tools are appropriately quantifying mood in this setting. We suggest that, in the perioperative period of a clinical trial, expectancy bias might drive the positive effects of ketamine, clinicians and patients report symptoms of depression differently, and patient-rated data on mood is unreliable.