Effects of Low-Dose Ketamine Infusion on the Positive and Negative Domains of Hopelessness and Suicidal Thoughts.
Wei-Chen Lin, Mu-Hong Chen, Tung-Ping Su, Cheng-Ta Li, Hui-Ju Wu, Shih-Jen Tsai, Ya-Mei Bai, Wei-Chung Mao, Pei-Chi Tu
The Journal of Clinical Psychiatry July 8, 2024 DOI: 10.4088/JCP.24m15257 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 84 |
| Population | Patients with treatment-resistant depression and strong suicidal ideation |
| Interventions | Ketamine Midazolam |
| Dose | 0.5 mg/kg ketamine or 0.045 mg/kg midazolam |
| Duration | Single infusion, assessments at 240 minutes and days 2, 3, 7, and 14 postinfusion |
| Topics | Esketamine Ketamine |
| Keywords | Mental health Ketamine therapy Suicide prevention Depression treatment Clinical research |
| Citations | 4 |
| Key findings | A single low-dose ketamine infusion produced a brief reduction in hopelessness at four hours and antisuicidal effects on day two postinfusion, with the early hopelessness reduction associated with the later antisuicidal effect. |
Abstract
Background: Low-dose ketamine infusion has been demonstrated to exert antisuicidal effects on patients with treatment-resistant depression (TRD) and strong suicidal ideation. Although evidence suggests an association between hopelessness and suicidality, very few studies have investigated the antihopelessness effects of ketamine.
Methods: This study included 84 patients with TRD and strong suicidal ideation. The diagnosis of depression was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for major depressive disorder. They were randomly assigned to receive a single infusion of either 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. Hopelessness and suicidal symptoms were assessed at baseline, at 240 minutes postinfusion, and on Days 2, 3, 7, and 14 postinfusion. The assessments were performed using the self-report Beck Hopelessness Scale (BHS) and Positive and Negative Suicide Ideation Inventory (PANSI). The analysis focused on the positive and negative domains of the BHS and PANSI, respectively. The clinical trial was conducted between August 15, 2018, and November 30, 2021.
Results: Statistical analyses performed using a generalized linear model revealed that the ketamine group had significantly higher PANSI-positive (P = .008) and lower PANSI-negative (P = .015) suicidal ideation scores on Day 2 postinfusion than did the midazolam group. At 240 minutes postinfusion, the ketamine group had significantly lower BHS-negative domain scores than did the midazolam group (P = .031). Notably, the observed ketamine-induced reduction in hopelessness at 240 minutes postinfusion was associated with its antisuicidal effect on Day 2 postinfusion.
Discussion: A single infusion of low-dose ketamine resulted in a brief (∼4 hours) yet significant reduction in hopelessness. Subjective antisuicidal effects of ketamine were noted on Day 2 postinfusion. Further studies are needed to elucidate the neuromechanisms underlying the antihopelessness and antisuicidal effects of ketamine.
Trial Registration: UMIN Clinical Trials Registry identifiers: UMIN000033916 and UMIN000033760.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 2
- Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode: A Systematic Review and Meta-Analysis. JAMA Psychiatry July 1, 2026
- Ketamine infusion therapy for treatment-resistant major depressive disorder and suicidal ideation: Nursing care and considerations. Nursing December 1, 2025