Strengths and limitations
MDD, toxicity, psychiatric
REGRESSION
To the authors’ knowledge, this study is the first prospective study providing key feasibility, safety, tolerability and potential antidepressant activity data for future definitive trial design exploring subcutaneous ketamine for MDD at dosages lower than the conventional psychiatric dose of 0.5mg/kg in a population with extremely short prognoses. It recruited despite multiple trial closures due to COVID-19. It included generous study eligibility criteria to allow for improved generalisability towards the palliative care population with significant co-morbidities and frailty. The individualised dose-titration study design minimised drug toxicity to participants. The monitoring of toxicity using standardised measures in psychiatry (i.e. BPRS and CADSS) and palliative care research (NCI CTCAE) allowed meaningful comparison of this study with the relevant literature.There were several limitations of the study for this study. Due to ethical and feasibility concerns, the study was designed as an open-label single-arm design without a placebo or an active comparator arm. This could inflate the true effect size of ketamine through potential assessor bias, Hawthorne effect, and regression to the mean [