Table 1 Study characteristics: randomized controlled trials.
Reference | Study Design; Country; Registration | Sample size (intervention vs control, if applicable) | Control Drug (if applicable) | Population | Intervention | Measure of suicidal ideation (SI) or behavior | Main Findings |
|---|---|---|---|---|---|---|---|
Zhou et al. [46] | Randomized double blind controlled trial; China; ChiCTR2000041232 | n = 54 (n = 27 vs n = 27) | IV midazolam (0.02 mg/kg) | 13–18 y/o inpatient adolescents with MDD and SI (C-SSRS Ideation score ≥ 1 and a SSI Item 4 or 5 score ≥2) | 3 infusions of IV S-ketamine (0.25 mg/kg) administered at Day 1, Day 3, and Day 5, along with standard inpatient treatment | Mean change in C-SSRSa and SSIb-5 | Based on C-SSRS score, S-ketamine improved SI from Day 2 till Day 6. According to the SSI-5, the S-ketamine group had more participants free of suicidal ideation up to Day 12. antidepressant effect was not as rapid as reported in adults. |
Leal et al. [23] | crossover, double-blind, placebo-controlled clinical trial; South America; UMIN000038347 | 10 (n = 10 vs n = 10 with a one-week interval) | IV saline (0.5 mg/kg) | 18–65 y/o participants with current MDD, without psychotic features, as assessed by the Mini International Neuropsychiatric Interview and depression (MADRS score of at least 25 at screening) | Participants received both interventions with a one-week interval. 5 participants received saline first, followed by R-ketamine (0.5 mg/kg). The other 5 received arketamine first, followed by placebo | No assessment of SI. Change in depression severity measured by the MADRSc | Arketamine was not superior to placebo in reducing depressive symptoms |
Fineberg et al. [42] | Exploratory, Parallel assignment, double-blind randomized control trial; US; NCT03395314 | 22 (n = 10 vs n = 12) | IV midazolam (0.04 mg/kg) | 21–60 y/o participants with a current mental health treater, SI, and current Borderline Personality Disorder | Single infusion of IV ketamine (0.5 mg/kg) | Change in BSSd total score | Ketamine was not superior to midazolam in reducing SI; the greatest magnitude of group effect on change in SI from baseline was observed at Day 1. |
Su et al. [44] | Randomized double blind controlled trial; Taiwan; UMIN000033916 and UMIN000033760 | 84 (n = 42 vs n = 42) | IV midazolam (0.045 mg/kg) | 20–64 y/o outpatients with TRD and SI (score of ≥ 4 on the MADRS item 10) | Single infusion of IV ketamine (0.5 mg/kg) | Total score for C-SSRSa-ISS subscale, MADRSc item 10, and PANSIe | The anti-SI effect of ketamine persisted to day 5. Ketamine’s anti-SI effects greater in patients with moderate and low refractoriness, whose current depressive episode lasted < 24 months or whose number of failed antidepressants was ≤4. |
Ahmed et al. [40] | randomized double-blind parallel-arm controlled trial; Egypt; NCT04101474 | 36 (n = 18 vs n = 18) | IV saline | 18+ y/o pts with TRD and current suicidal risk “based on psychiatric interview” (no cutoff provided) | 2 infusions of IV ketamine (0.5 mg/kg in 50 ml saline) administered each week for 2 consecutive weeks | Total SPSf score | Significant decrease in total SPS scores in ketamine compared to the control group up to 2 weeks; anti-SI response not influenced by other psychiatric symptoms or disorders |
Abbar et al. [39] | Double blind RCT, Prospective, superiority, placebo-controlled; France; NCT02299440 | 156 (n = 73 vs n = 83) | IV saline | 18–76 y/o inpatients with SI (SSI score > 3); stratified by diagnosis: bipolar disorder, depressive disorders or others | 2 infusions of IV ketamine (0.5 mg/kg) administered at baseline and 24 h, along with standard treatment | Remission evaluated by SSIb(total score ≤ 3 at follow-up) | Significantly greater remission of SI in ketamine group at Day3 compared to control group. Effect stronger in patients with bipolar disorder. Non-significant persistence of effect up to week 6 (p = 0.7) |
Domany et al. [48] | A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial; US; NCT02183272 | 30 (n = 15 vs n = 15) | Saline placebo | 18–65 y/o subjects, with SI (score ≥ 2 on the C-SSRS) and in need of psychiatric hospitalization | 4 IN applications of ketamine (10 mg each) in each nostril separated by 10 min each | Change in BSSb score; Remission evaluated by MADRSc-SI (score of 0) | At 4 h post-infusion, SI decreased in the treatment group. The between group difference was significant in the MADRS-SI scale but not the self-reported BSS scale. Remission from SI evident in 80% of the ketamine group compared with 33% for the controls. |
Ionescu et al. [51] | Double-blind, Randomized, Placebo-controlled multicenter study; US; Argentina; Austria; Belgium; Brazil; Canada; Czechia; France; Lithuania; Poland; Spain; Turkey; NCT03097133 | 230 (n = 115 vs n = 115) | Placebo nasal spray | 18–64 y/o subjects with MDD, active SI with intent (Responded “yes” to Mini International Neuropsychiatric Interview questions B3 and B10), and receiving standard care | Self-administered S-ketamine (84 mg) twice weekly for 4 weeks | SIBATg (includes CGIh–Severity of Suicidality–revised and of Imminent Suicide Risk and FoSTi) | Both groups experienced reduction in SI through Day 25 but between-group difference was not significant. |
Fu et al. [50] | Same as Canuso et al. [49] (see above); secondary analysis of pooled data from Aspire 1 & 2 | Same as Canuso et al. [49] | Same as Canuso et al. [49] | Same as Canuso et al. [49] | Same as Canuso et al. [49] | Same as Canuso et al. [49] | Based on the CGI-SS, there was no significant difference on SI at 24-hour endpoint throughout 4-week treatment |
Vieira et al. [45] | randomized, controlled, double-blind trial,naturalistic sample; South America UMIN000032355 | 59 (S-ketamine: n = 30; ketamine: n = 29) | No Placebo | 18+ y/o subjects with TRD and SI (score ≥ 1 for MADRS item 10) | Single IV infusion of S-ketamine (0.25 mg/kg) or racemic ketamine (0.5 mg/kg) over 40 min | Total MADRSc item 10 score | Ketamine and S-ketamine were equally effective in rapidly reducing SI in TRD subjects at 24 h and up to 7 days following infusion |
Kheirabadi et al. [47] | Randomized, Not blinded, No placebo, Parallel assignment; Iran; IRCT20090801002266N8 | 45 (ECT: n = 15; oral ketamine: n = 15; IM ketamine: n = 15) | No Placebo | 18–70 y/o pts with MDD referred for ECT; pts had one of the symptoms of SI, treatment resistance, severe symptoms, or agitation | 3 groups: 0.5 mg/kg of racemic IM ketamine; 1 mg/kg of racemic oral ketamine; or ECT in 6–9 sessions during 3 weeks. | SSIb | SI significantly improved in all groups compared to baseline with no between-group differences. Strongest anti-SI effect was at 24 h after first intervention in all groups. |
