Repeated-dose ketamine infusions did not have a significant effect in reducing depressive symptoms and suicidal ideation when compared with placebo in patients with severe treatment-resistant depression and current, chronic suicidal ideation, according to a study published in the Journal of Affective Disorders.

The investigators of this double-blind, placebo-controlled study sought to examine the short- and long-term antidepressant and antisuicidal effects of repeated-dose ketamine augmentation in patients with treatment-resistant depression who reported current, chronic suicidal ideation.

The study sample included 26 patients with severe major depressive disorder with current, chronic suicidal ideation and a history of 3 or more failed antidepressant treatment trials; participants were randomly assigned to receive 6 ketamine infusions (0.5 mg/kg) or saline placebo over 3 weeks. All patients were maintained on a stable outpatient medication regimen prior to the start of study and through the infusion phase. Antidepressant efficacy outcomes were measured using the Hamilton Depression Rating Scale; secondary antisuicidal efficacy was measured using both the Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation score and intensity rating. The study investigators assessed depression and suicidal ideation at baseline, 240 minutes post-infusion, and every other week during a 3-month follow-up period.

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As a whole, the participants’ depression scores decreased significantly over time, as did their C-SSRS suicidal ideation scores; however, no significant differences in depression severity (P =.47) or suicidal ideation (P =.32) were observed between ketamine and placebo groups across the infusion phase. Of the 26 participants, a total of 14 (54%) completed all visits (7 in each group). At the end of follow-up, 2 patients in the ketamine group and 3 patients in the placebo group met criteria for both antidepressant response and remission. In the ketamine group, 5 patients achieved the absence of suicidal ideation at the last infusion, but only 1 patient continued to meet absence criteria for suicidal ideation at the end of follow-up. In the placebo group, 3 patients reported absence of suicidal ideation at the last infusion, but only 2 continued to meet absence criteria through the end of the study.

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Limitations of the study include a small sample size restricted to outpatients, which may have resulted in lower levels of suicidal ideation by excluding individuals with more acute suicidal ideation that warrants hospitalization. Furthermore, outpatient medication regimens were uncontrolled; researchers could not rule out the impact of concomitant treatments on ketamine’s effect.

The study investigators found that while ketamine infusions reduced depressive symptoms and suicidal ideation among patients with severe treatment-resistant depression, there was no significant difference in the proportion of responders or remitters between the ketamine and placebo groups. However, they suggested that these results merit further exploration of ketamine’s potential to improve treatments for this high-risk population.

Disclosures: Multiple authors declare associations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.


Ionescu DF, Bentley KH, Eikermann M, et al. Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trialJ Affect Disord. 2019; 243:516-524.