Trial Outcomes & Findings for Inpatient Single Dose Interventions for Alcohol Use Disorder (NCT NCT04562779)

NCT ID: NCT04562779

Last Updated: 2024-05-02

Results Overview

Binary outcome: any all-cause hospitalization ascertained by chart review (our EHR includes records from several local hospitals). Note that it is not dependent on study completion, so it is analyzed by intent to treat.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 44 participants
• Primary outcome timeframe: Within 30 days of index hospital discharge. The enrollment period is 12 months.
• Results posted on: 2024-05-02

Participant Flow

Hospital.

Participant milestones

Measure	XR Naltrexone Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Overall Study STARTED	14	13	17
Overall Study COMPLETED	5	6	7
Overall Study NOT COMPLETED	9	7	10

Reasons for withdrawal

Measure	XR Naltrexone Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Overall Study Lost to Follow-up	7	5	10
Overall Study Protocol Violation	2	2	0

Baseline Characteristics

Inpatient Single Dose Interventions for Alcohol Use Disorder

Baseline characteristics by cohort

Measure	XR Naltrexone n=14 Participants Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine n=13 Participants Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage n=17 Participants Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Total n=44 Participants Total of all reporting groups
Age, Continuous	44.9 years STANDARD_DEVIATION 12.5 • n=5 Participants	43.9 years STANDARD_DEVIATION 11.5 • n=7 Participants	46.2 years STANDARD_DEVIATION 9.5 • n=5 Participants	45.1 years STANDARD_DEVIATION 10.9 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants	35 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants	28 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants	25 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment United States	14 participants n=5 Participants	13 participants n=7 Participants	17 participants n=5 Participants	44 participants n=4 Participants

PRIMARY outcome

Timeframe: Within 30 days of index hospital discharge. The enrollment period is 12 months.

Binary outcome: any all-cause hospitalization ascertained by chart review (our EHR includes records from several local hospitals).

Note that it is not dependent on study completion, so it is analyzed by intent to treat.

Outcome measures

Measure	XR Naltrexone n=14 Participants Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine n=13 Participants Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage n=17 Participants Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Rate (%) of 30-day Hospital Re-admission	3 Participants	2 Participants	7 Participants

PRIMARY outcome

Timeframe: The enrollment period is 12 months

Number of participants recruited per month during the enrollment period

Outcome measures

Measure	XR Naltrexone n=44 Participants Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Feasibility - Recruitment Rate (# Per Month)	3.7 participants per month recruited Standard Deviation 2.8	—	—

PRIMARY outcome

Timeframe: 14 days

Percentage of patients who presented to follow-up appointment within 14 days

Outcome measures

Measure	XR Naltrexone n=14 Participants Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine n=13 Participants Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage n=17 Participants Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Feasibility - Follow-up Rate (%)	7 Participants	8 Participants	7 Participants

SECONDARY outcome

Timeframe: Within 30 days of index hospital discharge. The enrollment period is 12 months.

Binary outcome: any all-cause ED visit ascertained by chart review

Outcome measures

Measure	XR Naltrexone n=14 Participants Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine n=13 Participants Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage n=17 Participants Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Rate (%) of 30-day Emergency Department Visit	8 Participants	7 Participants	12 Participants

Adverse Events

XR Naltrexone

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

IV Ketamine

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Linkage

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	XR Naltrexone n=14 participants at risk Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	IV Ketamine n=13 participants at risk Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up	Linkage n=17 participants at risk Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Gastrointestinal disorders diarrhea	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	7.7% 1/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Gastrointestinal disorders constipation	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Gastrointestinal disorders dry mouth	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Gastrointestinal disorders nausea/vomiting	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Gastrointestinal disorders abdominal pain	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Gastrointestinal disorders increased appetite	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Gastrointestinal disorders decreased appetite	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Cardiac disorders palpitations	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Cardiac disorders dizziness on standing	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Cardiac disorders chest pain	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Respiratory, thoracic and mediastinal disorders shortness of breath	14.3% 2/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	15.4% 2/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Respiratory, thoracic and mediastinal disorders cough	14.3% 2/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	7.7% 1/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Reproductive system and breast disorders cough	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Respiratory, thoracic and mediastinal disorders pain with breathing	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Skin and subcutaneous tissue disorders injection site reaction (naltrexone)	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Skin and subcutaneous tissue disorders injection site reaction	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Skin and subcutaneous tissue disorders rash	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Skin and subcutaneous tissue disorders increased perspiration	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Skin and subcutaneous tissue disorders itching	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Skin and subcutaneous tissue disorders dry skin	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	7.7% 1/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Nervous system disorders headache	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Nervous system disorders tremor	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	7.7% 1/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	11.8% 2/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Nervous system disorders poor coordination	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Nervous system disorders dizziness or lightheadedness	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Nervous system disorders numbness or tingling	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Nervous system disorders speech difficulty	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Eye disorders blurred vision	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	11.8% 2/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Ear and labyrinth disorders ringing in ear	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Renal and urinary disorders difficulty urinating	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Renal and urinary disorders painful urination	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Renal and urinary disorders frequent urination	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Reproductive system and breast disorders menstrual irregularity	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Reproductive system and breast disorders increased libido	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Reproductive system and breast disorders decreased libido	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	7.7% 1/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Psychiatric disorders difficulty sleeping	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	7.7% 1/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Psychiatric disorders abnormal dreams	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Psychiatric disorders anxiety	28.6% 4/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	15.4% 2/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Psychiatric disorders hallucinations	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Psychiatric disorders memory loss	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	7.7% 1/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	5.9% 1/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Psychiatric disorders poor concentration	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	15.4% 2/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
General disorders fatigue or decreased energy	28.6% 4/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	17.6% 3/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
Psychiatric disorders fatigue or decreased energy	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	15.4% 2/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
General disorders restlessness	7.1% 1/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	15.4% 2/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.
General disorders other	0.00% 0/14 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/13 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.	0.00% 0/17 • Immediate effects of IM naltrexone or IV ketamine were assessed immediately after administration in the hospital. Adverse events by PRISE questionnaire were assessed at follow-up visit (targeted at 1 week post-discharge) for those who attended. Deaths and serious adverse events would be detected at any point within 30 days post-discharge from electronic health record alerts, direct patient communication with study team, or other staff communication. Hospital admission or emergency department visits were not automatically considered serious adverse events. This is because these were the primary/secondary outcomes targeted by the intervention itself.

Additional Information

Dr. Dale Terasaki

Denver Health & Hospital Authority

Phone: 303-602-6922

Email: dale.terasaki@dhha.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place