ASPIRED: Alleviating Suicidality by Combining Psychotherapy and IM Ketamine for Rapid Treatment in the Emergency Department – A Randomized Clinical Trial

Suicide prevention in military personnel is one of the Defense Department’s highest priorities, as the annual number of suicide deaths continues to outpace combat-related deaths. Suicidal ideation and suicide attempts also account for the vast majority of behavioral health evacuations out of theater. There is great concern among veterans and civilians as well, as suicide rates have risen steadily in these populations the last 20 years.

The hospital emergency department is a key place to intervene. It is often a first-line access point for active military, reservists, and veterans experiencing acute changes in their mental health status. In addition to those presenting with overt suicidal ideation, suicidal thoughts are often secondarily discovered during an ER assessment. On the civilian side, up to half of individuals who die by suicide visited an ER during the year before their death.

But crowded emergency rooms are in a crisis themselves, often having to board psychiatric patients for prolonged times while awaiting an available bed for admission into a psychiatric facility. New and innovative approaches are needed to stem the tide of suicides in military, veteran, and civilian populations and to mitigate this national crisis in emergency departments.

This is the goal of a STRONG STAR-affiliated study led by Robert DeLorenzo, MD, MSCI, MSM, FACEP, of The University of Texas at San Antonio Long School of Medicine. The study team is evaluating the combination of an intramuscular (IM) ketamine injection and a brief (i.e., about 30 minutes), evidence-based, cognitive-behavioral therapy called Crisis Response Planning (CRP) to see if it leads to both a rapid and sustained reduction in suicide risk among patients visiting the ER for acute suicide ideation. The hope is that this novel intervention could alleviate the need for the patient’s hospitalization in the short term and continue to help save lives in the long term.

Study rationale

Ketamine, already approved for treating depression, has been shown in depression trials to rapidly reduce suicide risk. IM ketamine injections also are already used safely by ER physicians to decrease agitation in psychiatric patients and to help alleviate severe pain. In addition, this low-cost, generic medication is widely available in the U.S. and in combat theaters. However, IM ketamine has not been carefully studied specifically for suicide risk, including how long the reported decrease in suicide ideation lasts or what happens when it wears off.

On the other hand, evidence supports CRP for its long-term effectiveness with acutely suicidal patients, but its immediate and short-term effects remain largely unknown.

For these reasons, Dr. DeLorenzo and his team have designed a randomized clinical trial to evaluate the feasibility, safety, and effectiveness of IM ketamine injection and CRP for patients presenting with acute suicide risk in the ER. The researchers want to see whether this combination creates a synergistic effect on both short- and long-term outcomes. Comparison will be done with a saline injection as a placebo to ketamine and Safety Planning—a current standard intervention used with suicidal patients—as a control for CRP.

How the trial works

The study will be conducted in collaboration with the ERs at University Hospital in San Antonio, Texas, and at Carl R. Darnall Army Medical Center at Fort Hood, Texas. After patients have been evaluated, assessed, and assigned an inpatient bed in the hospital’s psychiatric unit, they will be invited to participate in the study. Those who consent will then be randomized to one of four treatment arms:

• Ketamine plus Crisis Response Planning (CRP)
• Ketamine plus Safety Planning (control)
• Normal Saline (placebo) plus CRP
• Normal Saline (placebo) plus Safety Planning (control)

Following these interventions, patients will be assessed 24, 48 and 72 hours later and again after 7, 14, 21, and 28 days. Researchers expect IM ketamine to take effect quickly and be associated with a significant reduction in suicidal ideation up to 7 days post-treatment. They also expect that this effect will be transitory and taper off over one to two weeks, but that CRP will show evidence of a sustained reduction of suicidal ideation at one to two months post-treatment.

Expected benefit

If the researchers’ hypothesis holds true, patients undergoing an acute suicidal crisis may see dramatic benefits from the results of this study, with a novel treatment method available to rapidly reduce suicidal thoughts, urges, and associated distress. In the civilian population, this will help avoid the problem of patients being held indefinitely in psychiatric emergency departments while awaiting definitive care or transfer. In the military population, the intervention could allow for safer transfer from combat zones, shorter off-duty periods, as well as improved unit cohesion by lessening the significant difficulties posed by suicidal ideation in service members.  In the end, the long-term reduction in symptoms could help save lives for years to come.