Trial PaperDepressive DisordersSuicidalityKetaminePlacebo

Single, Fixed-Dose Intranasal Ketamine for Alleviation of Acute Suicidal Ideation. An Emergency Department, Trans-Diagnostic Approach: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial

This double-blind placebo-controlled study study (n=30) with intranasal ketamine (40mg) found significant reductions in suicidal ideation (SI, 80 vs 33% remission) and depressive symptoms (MADRS) 4 hours after administration for those with SI in the emergency department.

Authors

  • Domany, Y.
  • McCullumsmith, C. B.

Published

Archives of Suicide Research
individual Study

Abstract

Background

Suicidal patients often present to the emergency department, where specific anti-suicidal treatment is lacking. Ketamine, a Glutamate modulator and a rapidly acting antidepressant with anti-suicidal properties, might offer relief.

Aims

Evaluation of single, fixed-dosed intranasal ketamine for acute suicidal ideation in the emergency department.

Methods

Between August 2016 and April 2018, 30 eligible suicidal subjects, scheduled for psychiatric hospitalization, independently of their psychiatric diagnosis, were randomized to intranasal ketamine 40 mg or saline placebo. Safety and efficacy evaluations were scheduled for 30, 60, 120, and 240 min post administration and on days 1, 2, 3, 4, 5, 7, 21, and 28. Primary outcome was suicidal ideation.

Results

Fifteen subjects were randomized for each study group. All were analyzed for primary and secondary outcomes. Four hours post administration, the mean difference in suicidal symptoms between the groups, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) item of suicidal thoughts (MADRS-SI), was 1.267 (95% confident interval 0.1-2.43, p < 0.05) favoring treatment. Remission from suicidal ideation was evident in 80% for the ketamine group compared with 33% for the controls (p < 0.05). The mean difference in depressive symptoms, measured by MADRS, at the same time was 9.75 (95% confident interval 0.72-18.79, p < 0.05) favoring ketamine. Treatment was safe and well-tolerated.

Conclusions

Single, fixed-dose, intranasal ketamine alleviated suicidal ideation and improved depressive symptoms four hours post-administration. We present here an innovative paradigm for emergency department management of suicidal individuals. Future larger-scale studies are warranted.

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Research Summary of 'Single, Fixed-Dose Intranasal Ketamine for Alleviation of Acute Suicidal Ideation. An Emergency Department, Trans-Diagnostic Approach: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial'

Introduction

Acute suicidal patients frequently present to emergency departments but lack rapid, specific pharmacological options; these individuals are often hospitalised for short stabilisation and discharged before conventional treatments have time to act. Suicide can cut across diagnostic categories, and a trans-diagnostic framing—treating suicidal ideation as a separable clinical target—may be especially useful in the emergency setting where immediate management is required. Earlier research indicates that ketamine, a glutamatergic modulator with a rapid antidepressant effect, can reduce suicidal ideation for hours to days after administration, and intranasal esketamine has been studied and approved for resistant depression, motivating investigation of intranasal routes for acute suicidality. Domany and colleagues set out to evaluate whether a single fixed dose of intranasal racemic ketamine is feasible, tolerated and efficacious for rapidly reducing acute suicidal ideation in adults presenting to an emergency department who required psychiatric hospitalisation, irrespective of their diagnostic category. The study aimed to test a practical emergency-department intervention (40 mg intranasal ketamine) and to assess suicidal ideation, depressive symptoms, remission rates and safety across a 28-day follow-up period.

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Study Details

  • Study Type
    individual
  • Journal
  • Compounds
  • Topics
  • APA Citation

    Domany, Y., & McCullumsmith, C. B. (2022). Single, Fixed-Dose Intranasal Ketamine for Alleviation of Acute Suicidal Ideation. An Emergency Department, Trans-Diagnostic Approach: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial. Archives of Suicide Research, 26(3), 1250-1265. https://doi.org/10.1080/13811118.2021.1878078

References (12)

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