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Principal Investigator: Peter R Chai
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $268,500
Funding agency: National Institute on Drug Abuse
Project summary
Emergency departments (ED) in the US have experienced a significant increase in admissions for opioid-related
overdoses and suicide attempts during the COVID pandemic. Individuals with opioid use disorder (OUD) have a
lifetime prevalence of suicide attempts exceeding 40%, along with elevated odds of a completed suicide. Among
the 100,000 drug-related overdose deaths in 2021—the largest number ever recorded in a 12-month period—
30% or more of such events may in fact be suicides. In 2017, there were over 960,000 ED visits in the US for a
non-fatal overdose, making the ED a critical setting in which to intervene. Behavioral interventions like Screening,
Brief Intervention, and Referral to Treatment (SBIRT) in the ED improve alcohol outcomes, but multiple trials
have failed to show any benefit of SBIRT for individuals with OUD. Structural barriers like ED crowding and lack
of follow up for addiction and psychiatric treatment also mar efforts to treat these diseases. Despite the increased
utilization of medications for OUD (MOUD) in the ED setting, most patients still do not receive MOUD in the ED,
and among those who do, the majority do not continue treatment after discharge. Therefore, there is a critical
need for research to identify treatments that can be delivered effectively and sustainably in the ED for individuals
with OUD particularly for those who are endorsing suicidal ideation. Ketamine has garnered interest due to its
potential in treating psychiatric disorders, rapidly diminishing depressive and suicidal symptoms among
individuals with treatment-resistant depression. Sub-anesthetic doses of ketamine administered in either single
or multiple sessions in conjunction with psychotherapy has shown beneficial effects for patients with alcohol,
opioid, and cocaine use disorders. A major advantage of ketamine is that it is already an accepted
pharmacotherapy used routinely in the ED for procedural sedation, agitation, and acute pain. If ketamine could
be used as an effective pharmacotherapy for OUD and suicidal ideation in the ED, the approach would be
consistent with Screening, Treatment Initiation, and Referral (STIR) which may be more beneficial than the
traditional SBIRT approach. However there remains a significant gap in understanding the safety of ED-initiated
ketamine for those with OUD in the ED. To fill this need, we propose to conduct a pilot, double-blind, placebo-
controlled randomized trial with the primary aim of assessing the safety of administering ketamine in the ED to
OUD patients who are endorsing suicidal ideation. Those who are eligible will be randomly assigned to receive
either a single infusion of ketamine or saline placebo. Vital signs, side effects, psychiatric adverse effects, opioid
withdrawal, and cravings for opioids and ketamine will be monitored closely throughout the ED admission. As a
secondary aim, we will determine the preliminary efficacy of ketamine on opioid- and suicide-related outcomes.
Mechanisms of behavior change will be explored. If successful, this line of research will help establish the safety
of ketamine administration for OUD in the ED, and facilitate the design of a larger efficacy trial.
Terms: <Accident and Emergency department><Active Follow-up><Acute><Acute Pain><Address><Admission><Admission activity><Adverse effects><Agitation><Alcohol Chemical Class><Alcohols><Anesthestic Drugs><Anesthetic Agents><Anesthetic Drugs><Anesthetics><Animals><Back><Behavior Conditioning Therapy><Behavior Modification><Behavior Therapy><Behavior Treatment><Behavioral Conditioning Therapy><Behavioral Mechanisms><Behavioral Modification><Behavioral Therapy><Behavioral Treatment><Blood Pressure><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cardiac Chronotropism><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Caring><Cocaine use disorder><Conditioning Therapy><Data><Diastolic Pressure><Diastolic blood pressure><Disease><Disorder><Dorsum><Dose><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Drug Therapy><Drugs><ED crowding><ED visit><ER visit><Eligibility><Eligibility Determination><Emergency Department><Emergency care visit><Emergency department crowding><Emergency department visit><Emergency hospital visit><Emergency room><Emergency room visit><Emotional Depression><Event><Face><Feeling suicidal><Foundations><Goals><Heart Rate><Heart Vascular><Human><Incidence><Individual><Infusion><Infusion procedures><Intervention><Intervention Strategies><Intravenous><Ketamine><Link><Mechanisms of Behavior and Behavior Change><Medication><Mental Depression><Mental disorders><Mental health disorders><Methods><Modern Man><Monitor><NIDA><National Institute of Drug Abuse><National Institute on Drug Abuse><Opiate Receptors><Opiates><Opioid><Opioid Receptor><Outcome><Outcome Assessment><Overdose><Pain><Painful><Participant><Patients><Pharmaceutical Preparations><Pharmacotherapy><Placebo Control><Placebos><Prevalence><Prevention><Protocol Screening><Psychiatric Disease><Psychiatric Disorder><Psychiatric therapeutic procedure><Psychomotor Agitation><Psychomotor Excitement><Psychomotor Hyperactivity><Psychomotor Restlessness><Psychotherapy><Public Health><Randomization trial><Randomized><Relapse><Reporting><Research><Restlessness><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SBIRT><Safety><Saline><Saline Solution><Sedation procedure><Serious Adverse Event><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Adverse Event><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Sham Treatment><Substance Use Disorder><Suicidal thoughts><Suicide><Suicide attempt><Symptoms><Tachycardia><Testing><Toxicology><Visit><active followup><addiction><addictive disorder><alcohol use disorder><anti-depressant effect><antidepressant effect><arm><behavior change><behavior intervention><behavior mechanism><behavioral intervention><circulatory system><co-morbid><co-morbidity><commit suicide><comorbidity><completed suicide><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><craving><depression><depression symptom><depressive><depressive symptoms><design><designing><drug misuse><drug treatment><drug/agent><efficacy trial><emergency settings><ethanol use disorder><experience><faces><facial><fatal attempt><fatal suicide><follow up><follow-up><followed up><followup><hemodynamics><hypertensive><improved><improved outcome><infusions><innovate><innovation><innovative><intent to die><interest><interventional strategy><medication for opioid use disorder><medication misuse><mental illness><non fatal attempt><nonfatal attempt><opiate consumption><opiate drug use><opiate intake><opiate overdose><opiate related overdose><opiate use><opiate use disorder><opiate withdrawal><opioid consumption><opioid detox><opioid detoxification><opioid drug overdose><opioid drug use><opioid induced overdose><opioid intake><opioid intoxication><opioid medication overdose><opioid overdose><opioid poisoning><opioid related overdose><opioid toxicity><opioid use><opioid use disorder><opioid withdrawal><overdose death><overdose fatalities><pharmacologic><placebo controlled><prevent><preventing><primary outcome><psychiatric care><psychiatric illness><psychiatric therapy><psychiatric treatment><psychological disorder><randomisation><randomization><randomized placebo control trial><randomized placebo controlled trial><randomized trial><randomly assigned><safety assessment><safety outcomes><screening><screening, brief intervention, and referral to treatment><screening, brief intervention, referral, and treatment><screenings><secondary outcome><sedation><serious adverse experience><serious adverse reaction><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sham therapy><side effect><substance misuse><substance use and disorder><suicidal><suicidal attempt><suicidal ideation><suicidal thinking><suicidality><suicide ideation><suicides><thoughts about suicide><timeline><treatment-refractory depression><treatment-resistant depression>