Limitations and future work
depression
SECONDARY
As a secondary analysis, this investigation has several limitations. First, the original study was primarily designed to investigate dose optimization, resulting in between-group differences in dose that were not the central focus of this secondary analysis. To address this limitation, we conducted the main statistical analyses for the complexity data across doses and conducted post hoc analysis examining main effects of dose. However, due to the Bayesian adaptive randomization strategy which resulted in very few participants being given ketamine at 0.1 or 0.25 mg/kg doses, this limited our power to examine complexity values and antidepressant response across these differing treatment arms. Our lack of findings of correlations between complexity values and their change and depression changes could be due to mixing lower dose ketamine in seven patients with the larger group of patients with typical sub-anesthetic doses (dose mixing effects are explored in the Supplementary Material). Future studies should investigate the relationship between ketamine, depression, and other physiological markers in larger samples. Second, this sample had a narrow age range. Future studies should examine patients in a cohort with more variability in age. Third, complexity allows us to study the richness and meaningfulness of a signal [In addition, because our study was a secondary analysis, it was outside the scope of this study to investigate the psychological correlates of complexity. One such important psychological construct is dissociation. Dissociation may have an important role in the relationship between ketamine and altered complexity. Previous work in healthy subjects has shown that associations of ketamine with increased signal diversity correlate with altered states of consciousness [