Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression

Abstract

Background: Intravenous ketamine has shown rapid antidepressant effects in early trials, making it a potentially attractive candidate for depressed patients at imminent risk of suicide. The Implicit Association Test (IAT), a performance-based measure of association between concepts, may have utility in suicide assessment.

Methods: Twenty-six patients with treatment-resistant depression were assessed using the suicidality item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) 2 hours before and 24 hours following a single subanesthetic dose of intravenous ketamine. Ten patients also completed IATs assessing implicit suicidal associations at comparable time points. In a second study, nine patients received thrice-weekly ketamine infusions over a 12-day period.

Results: Twenty-four hours after a single infusion, MADRS-SI scores were reduced on average by 2.08 points on a 0 to 6 scale (p < .001; d = 1.37), and 81% of patients received a rating of 0 or 1 postinfusion. Implicit suicidal associations were also reduced following ketamine (p = .003; d = 1.36), with reductions correlated across implicit and explicit measures. MADRS-SI reductions were sustained for 12 days by repeated-dose ketamine (p < .001; d = 2.42).

Conclusions: These preliminary findings support the premise that ketamine has rapid beneficial effects on suicidal cognition and warrants further study.

Trial registration: ClinicalTrials.gov NCT00419003 NCT00548964.

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 (Day 12 of study; Panel 2 only).

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. D-scores calculated as D = [(mean response latency during Escape/Me block − mean response latency during Escape/Not Me block) ÷ SD of response latency across all trials]. More positive D-score indicates stronger implicit self-identification with words related to “Escape,” in comparison to words related to “Stay.”