Can Immediate Post-injury Fluoxetine Improve the Recovery Trajectories of Victims in Bodily Trauma?

With this prospective double-blinded, placebo controlled clinical trial we hypothesize that immediate (post-injury) intervention with Fluoxetine will prevent/mitigate the development of negative psychiatric symptomology such as PTSD and depression for victims of bodily trauma. We also hypothesize that immediate use of Fluoxetine will decrease subjects' pain, pain interference and opioid use without changing our standard of care post-injury pain medication regimen. Enrolled subjects will be randomized to Fluoxetine or placebo at their index hospitalization.

Study Overview

• Status: Recruiting
• Conditions: Musculoskeletal Injury
• Intervention / Treatment: Drug: Fluoxetine; Drug: Placebo

Detailed Description

Upwards of 40-85% survivors of bodily trauma (in the civilian world most commonly motor vehicle accidents, falls and assaults), develop moderate to severe negative psychiatric symptomology following their injuries. (2,7) This symptomology can persist for years; at least 20% of patients with musculoskeletal trauma, specifically, display symptomology consistent with post-traumatic stress disorder (PTSD) symptomology up to three years following their injury. (8) Poor mental health outcomes are an independent risk factor for poor physical and social outcomes. (9,10) These symptoms, which are highly impairing, are complicated and heightened by loss of work/income following trauma, limited financial and social resources, and a large percentage of the population being uninsured/underinsured. Research has demonstrated that the pressures of poverty and low socioeconomic status alone predispose to PTSD symptomology and poor coping mechanisms, and this is compounded by decreased ability to obtain and pay for mental health care by those impoverished. There are significant barriers to mental health care for many adults, and these hurdles are even more insurmountable for those under or uninsured, minorities, and those in rural communities. (11) Very few victims of trauma who screen positive for psychological disorder receive mental health services following injury (12% at 3-months from injury), and if so, it is far removed from the injury (22% at 24-months from injury).

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jennifer Hagen, MD; Phone Number: 352-273-7016; Email: hagenje@ortho.ufl.edu
• Study Contact Backup: Name: MaryBeth Horodyski, EdD; Phone Number: 352-273-7074; Email: horodmb@ortho.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • Recruiting
      • University of Florida
      • Principal Investigator: Jennifer Hagen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Admitted to UF Health for trauma resulting in:

  • One or more extremity fractures requiring surgery
  • Pelvic Fracture
  • Chest/abdominal Injury requiring intervention in operating room
• Polytrauma (multiple organ systems/multiple fractures) or Beck Depression Inventory (BDI-II) ≥ 14

Exclusion Criteria:

• Severe Traumatic Brain Injury or cognitively not able to participate in surveys. (Glasgow Coma Scale 3-8)
• Other psychiatric conditions on current medical management (SSRI)
• Incarceration or Pregnancy
• Expected Injury Survival of less than 90 days
• Medical or physical condition in opinion of investigators that would preclude safe study participation
• Unable to provide informed consent due to language or other barriers
• Current or previous substance abuse (excluding cannabinoids and alcohol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects randomized to get Fluoxetine therapy; Subjects will be randomized to take Fluoxetine (10mg by mouth per day for first 14 days then 20 mg by mouth for 9 months). The randomized drug will be prescribed by the study team on the day of randomization so that the patient may be monitored for side effects during the remainder of their hospitalization. The patient will be prescribed the randomized medication on the day of discharge and a 90 day supply will be provided by the inpatient research pharmacy at the 2 week, 3 month, and 6 month follow-up visits	Drug: Fluoxetine; Subjects will be randomized to take Fluoxetine (10mg by mouth per day for first 14 days then 20 mg by mouth for 9 months). The randomized drug will be prescribed by the study team on the day of randomization so that the patient may be monitored for side effects during the remainder of their hospitalization. The patient will be prescribed the randomized medication on the day of discharge and a 90 day supply will be provided by the inpatient research pharmacy at the 2 week, 3 month, and 6 month follow-up visits
Active Comparator: Subjects randomized to Placebo; When a patient is enrolled, the inpatient research pharmacy will dispense the appropriately randomized medication in a visually similar, over-encapsulated form as Fluoxetine	Drug: Placebo; When a patient is enrolled, the inpatient research pharmacy will dispense the appropriately randomized medication in a visually similar, over-encapsulated form as Fluoxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Dression Inventory survey, in the post injury period for patients with musculoskeletal trauma.	BDI-II Beck Depression Inventory: higher score means worse outcome; 0-63.	Baseline up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported pain scores, PROMIS Pain Interference, will be recorded at each visit.	PROMIS PI: Pain Interference; A score of 50 is average; Adaptive so no minimum/maximum values.	Baseline up to 12 months

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Jennifer Hagan, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): March 17, 2027
• Study Completion (Estimated): March 17, 2027

Study Registration Dates

• First Submitted: September 5, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Organic Chemicals; Amines; Propylamines; Fluoxetine
• Other Study ID Numbers: IRB202301506

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No