Single-dose Ketamine for the Reduction of Pain and Depression in the Emergency Department

Study Overview
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Brief Summary
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In this proposal, the investigators will determine if a single dose of intravenous (IV) ketamine (in combination with midazolam) reduces pain severity, depressive symptoms and need for opiate analgesics both in the ED and in the acute recovery period after ED discharge. The investigators will compare the ketamine arm to an active placebo-controlled arm (with midazolam).

Detailed Description
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The investigators will enroll 120 medically stable adult patients who present to two Emergency Departments with a chief complaint of acute pain. The investigators will randomly assign subjects using a blocked randomization schedule to either: 1) a single dose of IV ketamine (0.3 mg.kg) + midazolam, or 2) placebo + midazolam. ED providers and patients will be blind to treatment allocation. All participants will complete measures of pain and mood scores every 30 minutes, and the investigators will record any analgesics administered in the ED until discharge. At 7-days and 14-days post- discharge, the investigators will measure summary reports of pain severity, mood, and analgesic medication used.

Official Title
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Single-dose Ketamine to Reduce Pain Severity, Depressive Symptoms and the Need for Opiates Both During and After Emergency Department Care

Conditions
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Acute Pain, Depression

Intervention / Treatment
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* Drug: Ketamine
* Drug: Midazolam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults between the ages of 18-65 A chief complaint of painful condition (pain score ≥ 5 on the numeric rating scale [NRS] from 0-10 with anchors of 0 = no pain and 10 = worst pain imaginable) Expected to be in the ED for at least 2 hours Exclusion Criteria: Non-English speaking Not medically suitable for ketamine per treating MD (e.g. medical condition where ketamine is contraindicated); ketamine or midazolam may be unsafe (e.g., known sensitivity, glaucoma, or other concerns) Not alert and oriented Active psychosis, self-injury, suicidal/homicidal intentions on initial evaluation by treating team Seeking treatment due to a mental health or substance use disorder History of chronic opioid use Prescribed opioid use within the past 24 hours Any use of recreational narcotics throughout lifetime Sensitivity or allergy or intolerance to ketamine, opioids, and/or benzodiazepines Weight > 170kg (375 lbs) Current neurological disease (e.g., multiple sclerosis, stroke, brain tumor, seizure disorder, etc.) Pregnancy Prisoner

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to either the experimental condition (ketamine + midazolam) or the active control condition (placebo + midazolam)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Participants will be assigned to receive a single dose of IV ketamine (0.3 mg.kg) + midazolam | Drug: Ketamine<br>* Ketamine is a medication approved by the US Food and Drug Administration (FDA) for anesthesia, sedation, and post-surgical pain treatment. It is not approved for emergency patients complaining of pain but is often used off-label. Ketamine may be useful for acute pain management and in treatment of depressed mood. The purpose of this study is to determine whether a single low dose of ketamine can relieve pain and reduce negative mood for 2 weeks after emergency department (ED) treatment.<br>Drug: Midazolam<br>* In this study, all patients will also receive midazolam. Midazolam is a sedative that typically makes people feel relaxed and is intended to increase comfort with ketamine and reduce anxiety.<br>|
| Active Comparator: Active Placebo Arm<br>Participants will be assigned to receive a single dose of IV placebo + midazolam | Drug: Midazolam<br>* In this study, all patients will also receive midazolam. Midazolam is a sedative that typically makes people feel relaxed and is intended to increase comfort with ketamine and reduce anxiety.<br>Drug: Placebo<br>* In this study, patients in the active comparator group will receive midazolam first, then placebo. A placebo is an inactive solution that looks like the study drug, but contains no active ingredients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity in the ED | Pain Numeric Rating Scale (PNRS)- this item is anchored to pain intensity right now on a scale from 0(no pain)-10 (worst pain imaginable) | Pain intensity rating in the ED at 1-hour post-study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity at Follow-Up | Pain Numeric Rating Scale (PNRS): this item is anchored to pain intensity within the past 7-days on a scale from 0 (no pain) to 10 (worst pain imaginable) | Pain Intensity at 1-week post-ED Discharge |