The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: results from a randomized double-blind study
A. Feeney, R. Hock, Marlene P. Freeman, M. Flynn, B. Hoeppner, D. Iosifescu, M. Trivedi, G. Sanacora, S. Mathew, C. Debattista, D. Ionescu, M. Fava, G. Papakostas
European Neuropsychopharmacology June 2, 2021 DOI: 10.1016/j.euroneuro.2021.04.024 via Semantic Scholar
Summary
A single intravenous infusion of ketamine may reduce suicidal ideation in patients with treatment-resistant depression for up to 30 days, but early effects diminish rapidly. In a double-blind randomized trial, 40 patients received ketamine and 16 received midazolam placebo; all had clinically significant suicidal ideation at baseline. By day 30, the ketamine group had a lower mean suicide score (2.03) than the placebo group (3.00). However, among those whose suicidal ideation initially resolved by day 3, there was no significant difference between groups in later scores. Recurrence of suicidal ideation was common in both groups. The findings suggest a possible role for ketamine as an adjunct to standard treatments.
Study at a glance
| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 56 |
| Population | Patients with treatment-resistant depression and clinically significant suicidal ideation |
| Keywords | Medicine Psychology |
| Citations | 33 |
| Registration | NCT01920555 |
| Key finding | A single intravenous ketamine infusion was associated with lower suicidal ideation scores at 30 days compared to midazolam placebo, but early anti-suicidal effects diminished rapidly and recurrence was common. |
Abstract
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. Trial registration: NCT01920555.