A single infusion of ketamine reduced scores on the MADRS-SI by an average of 2.08 points on a 0–6 scale (t25=6.42, p<.001; d=1.37), with 81% of patients achieving a rating of 0 or 1 24-hours post-infusion (; ). Of the 13 patients with clinically significant suicidal ideation at baseline (MADRS-SI scores ≥4), 8 (62%) received a rating of 0 or 1 24-hours post-infusion, 3 (23%) endorsed fleeting suicidal thoughts (ratings of 2 or 3), while 2 (15%) remained at or above a rating of 4. With change scores in non-suicide-related MADRS items (MADRS-totalnonSI) entered as a covariate, repeated-measures ANCOVA of baseline and 24-hour MADRS-SI scores was not significant (F1,24=.38, p=.54), suggesting ketamine’s anti-suicidal effects are mediated by depression reduction.
Ketamine effects on explicit and implicit suicidality
FIGURE 1 Individual patient scores on the Montgomery-Asberg Rating Scale—Suicide item at baseline (Day 1; 150 minutes prior to infusion), 24-hours following a single subanesthetic infusion of ketamine (Day 2), and 4-hours following the final repeated infusion (more ...)
In the TRD subsample completing baseline IATs (n=12), stronger “Escape=Me” implicit associations were associated with greater MADRS-SI scores (rho=.60; p=.04), and marginally with SIcomposite scores (rho=.57; p=.052), but not with non-suicide-related depression severity (MADRS-totalnonSI: rho=.24; p=.46). Baseline “Death=Me” associations were unrelated to other measures (ps >.34). In patients who repeated the measures 24-hours post-infusion (n=10), there was a reduction in “Escape=Me” associations (t9=3.76; p=.006; d=1.37)() and in BSI (t9=3.15; p=.012) and MADRS-SI (t9=5.24; p<.001). “Death=Me” associations were not significantly changed (t9=.658; p=.52). “Escape=Me” reductions were correlated with reductions in BSI (r=.65; p=.042), SIcomposite (r=.64; p=.048), and MADRS-SI at the trend level (r=.57; p=.09), but not with MADRS-totalnonSI changes (r=−.03; p=.94). “Death=Me” changes showed a trend-level association with BSI changes only (r=.60; p=.06). Most zero-order correlations were maintained or increased after controlling for change in MADRS-totalnonSI and baseline SIcomposite ().
FIGURE 2 Mean IAT-Escape D-scores (± SEM) representing the strength of association between words related to “Me” and words related to “Escape” at baseline and 24-hours following a single subanesthetic infusion of ketamine. (more ...)
Partial correlations between change scores (24-hours – baseline) in implicit and explicit suicidality measures, controlling for change in other depressive symptoms (MADRS, excluding suicidality item)
In patients who subsequently enrolled in the repeated-dose ketamine study (n=10), the first infusion again significantly reduced MADRS-SI scores (2.8-point mean decrease; t9=5.47, p<.001; d=2.17), with 90% of patients receiving a 24-hour rating of 0 (; ). Acute reductions were maintained throughout the 12-day treatment period by the 9 patients receiving repeated infusions (baseline-to-day-12 mean decrease=2.89; t8=5.12, p=.001; d=2.42), with no patient scoring >2 at any post-baseline assessment (before and after each infusion).