This open-label study (n=14) finds that ketamine (35mg/70kg) infusion significantly reduced suicidal ideation (SI) in patients in the emergency department (ED). The acceptability (willingness to try treatment) was also high (>70%) among patients and physicians. The study is the first to test this in the ED.
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Objective
Mood disorders complicated by suicidal ideation (SI) frequently present to the emergency department (ED) for care. Currently, patients with SI in the ED do not typically receive targeted interventions. Ketamine may have a role in treating SI within the ED because subanesthetic doses have rapid-acting antidepressant and antisuicidal properties.
Methods
This single-arm, open-label feasibility study enrolled 14 participants from the ED with acute SI who were awaiting voluntary admission to inpatient psychiatry to receive ketamine at 0.5 mg/kg, administered intravenously. Participants were assessed post administration to evaluate feasibility of administration in the ED and short-term effectiveness. Feasibility was determined by acceptability by patients and physicians as well as tolerability and ability to recruit participants into the study. Efficacy was assessed based on changes in (1) self-reported mood and (2) suicidal ideation pre- and postinfusion of ketamine.
Results
All patients reported severe depression and active SI at baseline. No serious adverse events were reported, and acceptability was rated highly by both participants and physicians (>70%). Two hours after receiving ketamine 0.5 mg/kg, the mean SI and somatic symptom burden were decreased compared to baseline (P < 0.001 and P = 0.005, respectively), and the mean self-reported mood was increased (P = 0.006). Improvements in mood and decreases in suicidality persisted at 6 hours.
Conclusions
Overall, ketamine was well tolerated, considered feasible by both participants and physicians, and demonstrated short-term efficacy. There is a growing body of evidence demonstrating the feasibility of ketamine administration in the ED, and larger randomized trials should be conducted to establish treatment recommendations for patients with SI in the ED.
L. and colleagues conducted a single-arm, open-label feasibility pilot in an emergency department (ED) setting. The study enrolled 14 participants presenting to the ED with acute suicidal ideation (SI) who were awaiting voluntary admission to inpatient psychiatry. Each participant received an intravenous infusion of ketamine at 0.5 mg/kg. Feasibility was defined primarily by acceptability of ketamine to participants and treating physicians, together with tolerability (for example adverse events and any infusion discontinuations) and the practical ability to recruit eligible patients in the ED. The trial’s primary efficacy endpoints were within-subject changes in self-reported mood and suicidal ideation from baseline (pre-infusion) to 2 hours post-infusion. Mood was measured with the Immediate Mood Scaler (IMS) and suicidality with the Columbia Suicide Severity Rating Scale (C-SSRS). Ketamine-related side effects and dissociative symptoms were measured with the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). Assessments were performed at baseline, 2 hours and 6 hours after infusion, and then daily while patients remained in the ED until inpatient disposition. Assessments were administered both by research assistants and self-report, and data were collected in REDCap. The extracted text does not clearly report further details of statistical analysis methods (for example models or handling of missing data).
The study enrolled 14 participants. At baseline all participants reported severe depression and active suicidal ideation. No serious adverse events were reported. Acceptability of the ketamine intervention was rated highly by both participants and physicians (reported as >70%). On the primary efficacy measures, two hours after receiving ketamine 0.5 mg/kg the mean suicidal ideation score and mean somatic symptom burden were reduced compared with baseline (reported P < 0.001 and P = 0.005, respectively), and mean self-reported mood increased (P = 0.006). The authors report that improvements in mood and reductions in suicidality persisted at 6 hours post-infusion. Reported side effects and physical symptoms measured by SERSDA decreased after receiving ketamine compared with baseline. Treatment response was heterogeneous: roughly half of participants experienced marked improvements in mood and suicidality, while the remainder remained relatively stable over the observation period. The extracted text notes one participant died by suicide two months after participation; this event was determined by the authors to be unrelated to the ketamine intervention. The Results section indicates that assessments were completed using REDCap and that feasibility and efficacy were the trial’s two primary endpoints.
This pilot study had 2 primary end points: feasibility and efficacy. Feasibility was determined primarily by acceptability of ketamine by participants and physicians, with tolerability (eg, adverse events [AEs], discontinuation of the infusion due to AEs) and ability to recruit participants into the study also considered. The primary efficacy outcome was the change in mood and suicidality scores pre infusion (baseline) and 2 hours post infusion, specifically changes in (1) self-reported mood and (2) suicidal ideation pre and post infusion of ketamine using the Immediate Mood Scaler (IMS) and the Columbia Suicide Severity Rating Scale (C-SSRS), respectively.Ketamine side effects were assessed pre and post infusion using the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA).Participants completed the IMS, C-SSRS, and SERSDA at baseline (pre infusion), 2 and 6 hours post infusion, and daily while in the ED until inpatient disposition. Assessments were both RA-and selfadministered and were completed in REDCap software.
In this small open-label pilot, ketamine was tolerated, acceptable to patients and physicians, and had promising short-term efficacy. To our knowledge this is also the first study to evaluate an infusion of 0.5 mg/kg.These study findings add to the growing and compelling evidence on the effectiveness of ketamine for acute SI. On average, participants had substantial and sustained improvements in mood and suicidality over 6 hours when compared to baseline. Reported side effects and physical symptoms associated with ketamine administration actually decreased after receiving ketamine. A plausible explanation is that high somatic symptomatic burden at baseline is driven by the mood disturbance and SI and thus relieved by ketamine.Interestingly, treatment response was not uniform across the participants (Figure); roughly half the participants had marked improvements, whereas the remainder remained relatively stable over time. Future studies might further evaluate heterogeneity of treatment effect-whether there is a subgroup of patients who would particularly benefit from receiving ketamine in the ED. One participant completed suicide 2 months after their participation in the study. Although this event was determined to be unrelated to the ketamine intervention, it underscores that we identified patients at the highest risk of suicide for inclusion in the study. It also highlights the importance of long-term follow-up for patients with acute SI, particularly because these symptoms are often chronic.This study adds to the existing evidence that low-dose ketamine is effective for acute SI management and crisis stabilization. Currently, ketamine should not be viewed as a curative treatment in the ED, but as a bridging therapy to definitive care. Ketamine intervention should be considered a first step that assists suicidal individuals in getting connected with longterm care and ongoing supports like psychotherapy and antidepressant medications to address their underlying mood disorders. Overall, this promising feasibility study of low-dose ketamine lays the foundation for future larger studies that further establish safety
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Burger, J., Capobianco, M., Lovern, R. et al. · Military Medicine (2016)
Domany, Y., McCullumsmith, C. B. · Archives of Suicide Research (2021)
The authors interpret the findings as supporting the feasibility, tolerability and short-term efficacy of low-dose ketamine (0.5 mg/kg IV) for acute management of suicidal ideation in the ED. They state that ketamine was acceptable to both patients and physicians, produced rapid improvements in mood and reductions in suicidality within 2 hours that were sustained to 6 hours, and was not associated with serious adverse events in this small sample. L. and colleagues position these results as adding to a growing body of evidence that ketamine can be administered in ED settings for crisis stabilisation, while emphasising that ketamine should not be regarded as a curative intervention in the ED but rather as a bridging therapy to connect patients to longer-term care (for example psychotherapy and antidepressant medications). The authors suggest a possible explanation for the observed reduction in somatic symptoms is that somatic burden at baseline was driven by mood disturbance and SI and thus improved as mood improved. Key limitations acknowledged by the authors include the small, open-label single-arm design and heterogeneity of treatment response across participants. They note the need to further evaluate whether particular subgroups derive larger benefits and to establish longer-term safety and effectiveness through larger studies. The authors also highlight the one-post study suicide as a reminder that participants were a high-risk group and that long-term follow-up is important, although they report this death was judged unrelated to study treatment. Future research priorities they state are larger controlled trials to confirm safety and efficacy and investigations into heterogeneity of treatment effect and longer-term outcomes.
The authors conclude that low-dose ketamine (0.5 mg/kg IV) administered in the ED was feasible, well tolerated and showed promising short-term efficacy for reducing suicidal ideation and improving mood. They recommend viewing ketamine as a bridging intervention to support connection to definitive, longer-term psychiatric care rather than as a curative treatment, and call for larger studies to further establish safety, effectiveness and which patients are most likely to benefit.