Anhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials.
Elizabeth D. Ballard, Kathleen E. Wills, Níall Lally, Erica M. Richards, David A. Luckenbaugh, Tessa Walls, Rezvan Ameli, Mark J. Niciu, Nancy E. Brutsché, Lawrence T. Park, Carlos A. Zarate
Journal of Affective Disorders August 15, 2017 DOI: 10.1016/j.jad.2017.04.057 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post-hoc analysis of pooled clinical trial data Peer reviewed |
|---|---|
| Population | Treatment-resistant patients with major depressive disorder or bipolar disorder experiencing a major depressive episode, drawn from several clinical trials of ketamine |
| Intervention | Ketamine |
| Duration | One day post-ketamine administration (outcome assessment) |
| Measures | Beck Depression Inventory (BDI) anhedonia subscale, Snaith-Hamilton Pleasure Scale (SHAPS), Scale for Suicide Ideation (SSI5) subscale |
| Topics | Depression Ketamine Esketamine |
| Keywords | Anhedonia Rdoc Suicide |
| Key findings | Anhedonia measured by the Snaith-Hamilton Pleasure Scale was associated with suicidal thoughts independent of depressive symptoms both before and after ketamine administration; one day post-ketamine, SHAPS improvements accounted for an additional 13% of the variance in suicidal thought reduction beyond depressive symptoms. The Beck Depression Inventory anhedonia subscale was not significantly associated with suicidal thoughts after adjusting for depressive symptoms. The authors suggest these results have implications for ketamine's mechanisms of action on suicidal thoughts. |
Abstract
Identifying clinical correlates associated with reduced suicidal ideation may highlight new avenues for the treatment of suicidal thoughts. Anhedonia occurs across psychiatric diagnoses and has been associated with specific neural circuits in response to rapid-acting treatments, such as ketamine. This analysis sought to evaluate whether reductions in suicidal ideation after ketamine administration were related to reduced levels of anhedonia, independent of depressive symptoms. This post-hoc analysis included treatment-resistant patients with either major depressive disorder (MDD) or bipolar disorder (BD) from several clinical trials of ketamine. Anhedonia was assessed using a subscale of the Beck Depression Inventory (BDI) and the Snaith-Hamilton Pleasure Scale (SHAPS). The outcome of interest was suicidal ideation, as measured by a subscale of the Scale for Suicide Ideation (SSI5), one day post-ketamine administration. Anhedonia, as measured by the SHAPS, was associated with suicidal thoughts independent of depressive symptoms both before and after ketamine administration. One day post-ketamine administration, improvements on the SHAPS accounted for an additional 13% of the variance in suicidal thought reduction, beyond the influence of depressive symptoms. The BDI anhedonia subscale was not significantly associated with suicidal thoughts after adjusting for depressive symptoms. Data were limited to patients experiencing a major depressive episode and may not be generalizable to patients experiencing an active suicidal crisis. Suicidal thoughts may be related to symptoms of anhedonia independent of other depressive symptoms. These results have implications for the potential mechanisms of action of ketamine on suicidal thoughts.
Comparable studies
Other non-randomized and open-label trials on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder | 2010 | Open-label trial | n = 33 |
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression | 2020 | Open-label pilot trial | n = 7 |
| A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... | 2024 | Open label study | n = 17 |
| Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... | 2014 | Pooled analysis of three clinical trials | n = 97 |
Citations in the library
Cited by 29
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants The Annual Review of Pharmacology and Toxicology October 9, 2018
- Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β1 Translational Psychiatry January 27, 2020
and 24 more in the library
Cites 9
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial Psychological Medicine August 12, 2015
- Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression Translational Psychiatry October 14, 2014
- Neural correlates of change in major depressive disorder anhedonia following open-label ketamine Journal of Psychopharmacology February 17, 2015
and 4 more in the library