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

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. ClinicalTrials.gov Identifier: NCT02183272.

Keywords:

• Ketamine
• intra-nasal
• suicidal ideation
• emergency department

ACKNOWLEDGEMENTS

First of all, we would like to acknowledge our participants and their families, we would like to thank AFSP for their support. Special gratitude to Caleb Adler, Eric Nelson, Jadienne Lord, Shaul Schrieber, Mark Wieser, Rebeca J. Ackerman-Raphael, Ricardo Tarrasch, and Keren Armoni-Domany for their help and support.

Additional information

Funding

This study was supported by the American Foundation for Suicide Prevention (AFSP), 2015 Standard Research Innovation Grant for Chery B. Mccullumsmith.

Notes on contributors

Yoav Domany

Yoav Domany, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA; Department of Psychiatry, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Cheryl B. McCullumsmith

Cheryl B. McCullumsmith Department of Psychiatry, College of Medicine & Life Sciences, University of Toledo, Toledo, OH, USA