OBJECTIVE: Ketamine has disputed effects on suicidal ideation scores in depressed populations. This study assessed effectiveness of ketamine in adults with treatment resistant depression, examining a secondary outcome of suicidal ideation.
METHODS: Phase III, double-blind, randomized, active-controlled, multicenter trial. Participants were randomized to twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks; cohort 1 (n = 68) fixed-dose and cohort 2 (n = 106) flexible-dose. Analyses were cumulative link mixed models for change scores (baseline to treatment end), comparing ketamine versus midazolam (active control) for suicidal ideation, using the MADRS item 10 (planned) and C-SSRS (). post hoc
RESULTS: Mean baseline ideation scores were low (MADRS-10 cohort 1: 1.93 and cohort 2: 2.0). Cohort 1 had no significant difference between intervention and control: MADRS-10 β = 0.97, (95% CI=-0.95 to 2.90, p = 0.32), C-SSRS β = 0.64, (95% CI=-1.27 to 2.55, p = 0.51). Cohort 2 had a non-significant reduction for MADRS-10: β -0.61 (95% CI=-1.65 to 0.44, p = 0.25), but a significant reduction for C-SSRS: β-1.32 (95% CI=-2.51 to -0.12, p = 0.03). Participants had a higher C-SSRS score than the previous session, each of which triggered a clinical review, in 13.8% of all treatment sessions.
CONCLUSIONS: Subcutaneous, flexible-dosed, racemic ketamine over four weeks showed beneficial effects on suicidal ideation scores. Future studies should use suicidal ideation powered as a primary outcome, sample the full range of ideation scores, use consensus instruments, and explore treatment discontinuation, in various depressed populations.
