Discordant signals: How outcome measurement shapes interpretation of ketamine response in treatment-resistant depression.

BACKGROUND: Depression rating scales capture heterogeneous symptom domains, raising questions about the comparability of treatment response across instruments. This issue is particularly relevant for rapid-acting interventions such as ketamine. METHODS: We conducted a secondary analysis of a naturalistic cohort (N = 71) of patients with treatment-resistant depression treated with intravenous ketamine. Changes in depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory-II (BDI-II), and Clinical Global Impression-Severity (CGI-S). We examined correlations between change scores, magnitude of improvement across instruments, and changes in suicidality items. RESULTS: Change scores demonstrated variable associations across instruments. BDI-II and CGI-S change scores were strongly correlated (ρ = 0.69, p < 0.001), whereas MADRS showed weaker association with CGI-S (ρ = 0.13, p = 0.52) and moderate association with BDI-II (ρ = 0.46, p = 0.009). Mean percent reduction was greater for MADRS (54.2%) than BDI-II (41.9%), with correspondingly larger effect sizes (d = 1.78 vs d = 1.34). Suicidality improved on both measures, with a larger effect size for the clinician-rated MADRS item (d = 0.94) than the self-rated BDI-II item (d = 0.65). CONCLUSIONS: Depression rating scales provide non-equivalent estimates of ketamine treatment response. Outcome measurement influences effect size estimates and magnitude of improvement, supporting a multidimensional approach to characterizing antidepressant response.