521 - A Pilot Randomized Controlled Trial of Ketamine Infusion for Rapid Reduction of Suicidal Ideation in a Pediatric Emergency Department

Publication Number: 521.3617

Yury Onikashvili, University of British Columbia Faculty of Medicine, Maple Ridge, BC, Canada; Heather Burt, University of British Columbia Faculty of Medicine, Toronto, ON, Canada; Garth D. Meckler, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Jeffrey N.. Bone, BC Children's Hosiptal Research Institute, Vancouver, BC, Canada; Roberto Sassi, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Kendra Sih, British Columbia Children's Hospital, Vancouver, BC, Canada; Karly Stillwell, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Tyler Black, University of British Columbia, Vancouver, BC, Canada; Tatsuma Hind, Queen's University Faculty of Health Sciences, Vancouver, BC, Canada; Quynh Doan, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada

Background: Emergency department (ED) visits by youth with suicidal ideation (SI) have risen disproportionately, significantly impacting health resources. Though a few randomized control trials (RCTs) provide promising evidence of low-dose ketamine efficacy for rapid reduction of SI, as of writing, none have been published on youth in the ED.

Objective: This pilot study explored the feasibility of a ketamine-for-SI RCT in the pediatric ED.

Design/Methods: Single-center, 3-arm, triple-blind, pilot RCT comparing intravenous ketamine (0.5mg/kg), midazolam (active placebo, 0.03mg/kg), and saline (0.9%) in youth 10-17, requiring hospitalization and endorsing SI on the Columbia Suicide Severity Rating Scale, Severity Subscale (C-SSRS-SS). Participants were excluded if they had recent (3 month) ketamine or benzodiazepine use, conditions contraindicating trial interventions, or lacked a parent to consent. The primary outcome was distribution of SI scores on the C-SSRS-SS questions 3-5, Montgomery-Åsberg Depression Rating Scale SI item (MADRS10), and a pragmatic SI question (PQ) at 90 minutes post-infusion. Secondary outcomes of feasibility included reasons for non-enrolment, follow-up retention, adverse events, and assessment of blinding.

Results: Of 254 screened subjects, 40 were eligible (15.7%), of whom 15 were randomized (37.5%). Top 3 reasons for individuals screened but not enrolled were: staff/drug availability, no parent, and conditions contraindicating intervention (figure 1). Demographic characteristics and baseline SI scores are reported in table 1. The median [IQR] C-SSRS-SS, MADRS10 and PQ scores at 90 minutes were 0 [0, 2], 4 [2, 4], 5 [5, 6] for ketamine; 0 [0, 3], 3 [3, 6], 6 [3, 7] for midazolam; and 3 [2, 3], 4 [4, 5], 6 [6, 7] for saline. Retention rate at 7, 14, 21, 28-days was 93%, 87%, 73%, and 73%. No serious/unexpected adverse events occurred. Nurses, participants, and researchers correctly identified treatment arm 33%, 13% and 47% of the time.

Conclusion(s): This pilot demonstrates the feasibility of conducting a RCT of ketamine for the treatment of acute SI in youth in the ED and provides useful insights into future trial considerations. The pilot identified no safety events, had high rates of follow-up, and suggested the necessity/feasibility of an active placebo. Considering dedicated research nurses and a mature-minor consent process could help overcome two main barriers to enrolment. Within-group variability of different SI measures and the high proportion of non-cisgender participants highlight additional areas for consideration. Small sample size precludes inferences regarding treatment efficacy.

Figure 1. CONSORT study flow diagram
Reasons for not enrolling included top right. PED: Pediatric Emergency Department.

Table 1. Participant characteristics and baseline scores by each arm


Figure 2. Median participant scores, all time points
C-SSRS-SS: Columbia Suicide Severity Rating Scale, Severity Subscale. MADRS: Question 10 from the Montgomery-Asberg Depression Rating Scale. Pragmatic (0-10): a pragmatic questionnaire asking participants to rate suicidal ideation from 0-10. C-SSRS-SS scores were not collected past the 24 hour time-point, as it required a rater to ask structured interview questions, and the later follow-ups were self-reported data collections via email survey.

Figure 1. CONSORT study flow diagram
Reasons for not enrolling included top right. PED: Pediatric Emergency Department.

Table 1. Participant characteristics and baseline scores by each arm


Figure 2. Median participant scores, all time points
C-SSRS-SS: Columbia Suicide Severity Rating Scale, Severity Subscale. MADRS: Question 10 from the Montgomery-Asberg Depression Rating Scale. Pragmatic (0-10): a pragmatic questionnaire asking participants to rate suicidal ideation from 0-10. C-SSRS-SS scores were not collected past the 24 hour time-point, as it required a rater to ask structured interview questions, and the later follow-ups were self-reported data collections via email survey.