Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study.
Dawn F. Ionescu, Michaela B Swee, Kara J. Pavone, Norman E. Taylor, Oluwaseun Akeju, Lee Baer, Maren Nyer, Paolo Cassano, David Mischoulon, Jonathan E. Alpert, Emery N Brown, Matthew K. Nock, Maurizio Fava, Cristina Cusin
The Journal of Clinical Psychiatry June 2016 DOI: 10.4088/jcp.15m10056 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label secondary analysis of a clinical trial Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Outpatients with DSM-IV-diagnosed treatment-resistant major depressive disorder and current, stable (at least 3 months) suicidal thoughts |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3 |
| Duration | 6 infusions over 3 weeks, with assessments at 240 minutes postinfusion and naturalistic follow-up for 3 months |
| Measures | Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation scale, C-SSRS Intensity scale, Suicide Item of the 28-item Hamilton Depression Rating Scale (HDRS28-SI), 6-item Hamilton Depression Rating Scale (HDRS6) |
| Topics | Esketamine Ketamine |
| Registration | NCT01582945 |
| Key findings | Repeated open-label ketamine infusions were associated with rapid remission of suicidal ideation in 7 of 14 patients (50%) during the acute treatment phase, even among those whose depression did not remit, with significant linear decreases on the C-SSRS Ideation, C-SSRS Intensity, and HDRS28-SI scales. Two of the seven remitters (29%) maintained remission through a 3-month naturalistic follow-up. |
Abstract
Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥ 3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS₂₈-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P < .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS₆) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P < .01) and HDRS₂₈-SI (P < .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up. In this preliminary study, repeated doses of open-label ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients. ClinicalTrials.gov identifier: NCT01582945.
Comparable studies
Other non-randomized and open-label trials on ketamine, most cited first.
Citations in the library
Cited by 49
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial American Journal of Psychiatry December 5, 2017
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
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