The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: Results from a randomized double-blind study

This randomized double-blind placebo-controlled study (n=56) found that a single dose of ketamine significantly reduced the level of suicidal ideation (SI). Still, in both groups, there was a high level of suicidal ideation, and the study showed diminishing results rapidly over the 30 days of the study (the effects being the largest at 3 days post-infusion).


This study aimed to assess the effect of a single infusion of intravenous (IV) ketamine on suicidal ideation in patients with treatment-resistant depression (TRD). Patients with TRD were randomized in a double-blind fashion to a single infusion of IV ketamine or IV midazolam placebo. Suicidal ideation was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) suicide item at 3, 5, 7, 14 and 30 days post infusion. Clinically significant suicidal ideation was defined as a MADRS suicide item score ≥2. Forty patients who received IV ketamine and 16 who received IV midazolam had suicide item scores of ≥2 at baseline (IV ketamine group mean 2.90±0.74; IV midazolam group 2.69±0.70). The mean suicide scores of these groups differed significantly from each other on day 30; the IV ketamine group had a lower mean score than controls (2.03±1.59 vs. 3.00±1.41, t-test p = 0.049; Hedges’ g 0.71). Among patients with a suicide score of ≥2 at baseline and <2 at day 3, the two groups did not differ significantly on mean scores changes at days 3, 5, 7, 14 or 30. Recurrence of suicidal ideation was extensive in both treatment groups. A single infusion of IV ketamine may reduce suicidal ideation in TRD out to 30 days post infusion, but early anti-suicidal effects appear to diminish rapidly. This post-hoc analysis was not powered to compare different doses of ketamine. A single infusion of IV ketamine might have a role as an adjunct to standard treatments in patients with TRD and suicidal ideation.

Authors: Anna Feeney, Rebecca S. Hock, Marlene P. Freeman, Martina Flynn, Bettina Hoeppner, Dan V. Iosifescu, Madhukar H. Trivedi, Gerard Sanacora, Sanjay J. Mathew, Charles Debattista, Dawn F. Ionescu, Maurizio Fava & George I.Papakostas


Author highlights:

  • “Patients with resistant depression and suicidal ideation got a single dose of ketamine or placebo.
  • Those who received ketamine had lower suicide scores 30 days after the infusion.
  • However, recurrence of suicidal ideation was extensive in both groups.
  • Ketamine may have a role as an adjunct to standard treatments in this patient group.”

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Study details

Compounds studied

Topics studied

Study characteristics
Placebo-Controlled Double-Blind Randomized


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