Fluoxetine for Post-Traumatic Mental Health in Musculoskeletal Injuries

Overseen By Mary Beth Horodyski, EdD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Antidepressants

Disqualifiers: Traumatic brain injury, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 6-12 months

150 Participants Needed

Trial Summary

What is the purpose of this trial?

Musculoskeletal trauma is one of the leading causes of disability in the United States and its negative quality of life impact extends beyond that of physical recovery. More than 50% of victims of musculoskeletal trauma suffer lasting mental health issues following their injury. These symptoms can develop across all spectrums of patients with a variety of injury severities. Previously, this research team developed a ten-step program with the aim of developing fostering coping mechanisms in trauma patients. We were unable to demonstrate a measurable benefit to their mental health or physical function. This has been mirrored in other studies as well; talk therapy and support groups are not a strong enough intervention for some patients. We hypothesize that a subset of the trauma population would benefit from medical treatment for their depressive and anxious symptoms in the early recovery period. Given the limited resources of mental health systems, it would be ideal for their surgical providers to be able to manage safely their post-injury mental health issues during their surgical follow up. This is a pragmatic pilot study to develop an effective, acceptable, time-limited treatment strategy that could be safely implemented by non-mental health care providers for victims of musculoskeletal trauma.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications. However, if you have a history of certain mental health conditions and are on medication for them, you may be excluded from participating.

What data supports the effectiveness of the drug fluoxetine for post-traumatic mental health in musculoskeletal injuries?

Research shows that fluoxetine can help improve symptoms of post-traumatic stress disorder (PTSD), as it was more effective than a placebo in reducing PTSD symptoms in veterans. Additionally, fluoxetine has been shown to reduce the risk of relapse in PTSD patients compared to a placebo. ^{1 2 3 4 5}

Is fluoxetine generally safe for humans?

Fluoxetine, also known as Prozac, is generally considered safe for long-term use in humans. It has a lower risk of side effects compared to some other antidepressants, is safe in overdose, and can be used safely during pregnancy without causing birth defects. ^{2 6 7 8 9}

How is the drug fluoxetine unique in treating post-traumatic mental health issues in musculoskeletal injuries?

Fluoxetine, commonly known as Prozac, is unique because it is a selective serotonin reuptake inhibitor (SSRI) that is primarily used to treat depression and anxiety disorders, but it is being explored for its potential to help with post-traumatic mental health issues in musculoskeletal injuries. This is novel as there are no standard treatments specifically for this condition, and fluoxetine's ability to improve mood and reduce stress may aid in recovery. ^{1 4 9 10 11}

Research Team

Jennifer Hagen, MD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults over 18 with musculoskeletal trauma needing surgery, under the care of UF Orthopedic Trauma Division. It's not for those with traumatic brain injury, bipolar disorder or other managed mental health conditions, or who live too far from Gainesville to follow up.

Inclusion Criteria

I am 18 or older with a fracture needing surgery, under UF Orthopedic Trauma care.

Exclusion Criteria

patients unlikely to follow up (live in at a distance from Gainesville, incarcerated etc.) will also be excluded.

I do not have a traumatic brain injury or a managed mental health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either Fluoxetine or Calcium supplementation during hospitalization and continue post-discharge

6-12 months

4 visits (in-person) at 2 weeks, 3 months, 6 months, and 12 months

Follow-up

Participants are monitored for safety, mental well-being, and post-operative complications

12 months

4 visits (in-person) at 2 weeks, 3 months, 6 months, and 12 months

Treatment Details

Interventions

• Fluoxetine

Trial Overview The study tests if Fluoxetine (an antidepressant) and Calcium can help improve mental health in patients recovering from musculoskeletal injuries. The goal is to find a treatment that surgical teams can manage without specialized mental health providers.

Participant Groups

Group I: Subjects randomized to get Fluoxetine therapy Experimental Treatment 1 Intervention

Subjects will be randomized to take Fluoxetine (10mg by mouth per day). The randomized drug will be prescribed by the orthopedic team on the day 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.

Group II: Subjects randomized to get Calcium Supplmentation Active Control 1 Intervention

Subjects will be randomized to take Calcium supplementation (1000mg by mouth per day). The randomized drug will be prescribed by the orthopedic team on the day 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.

Fluoxetine is already approved in United States, European Union for the following indications:

Approved in United States as Prozac for:

• Depression
• Anxiety
• Obsessive-compulsive disorder
• Bulimia nervosa
• Panic disorder

Approved in European Union as Prozac for:

• Major depressive episodes
• Obsessive-compulsive disorder
• Bulimia nervosa

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Findings from Research

In a one-year trial involving 123 subjects with posttraumatic stress disorder, fluoxetine (FLU) significantly reduced relapse rates to 22% compared to 50% for the placebo group, indicating its efficacy in preventing relapse.

The study found that fluoxetine was well tolerated, and the time to relapse was longer for those on FLU compared to those on placebo, suggesting it may provide a protective effect against relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy with fluoxetine in posttraumatic stress disorder: a placebo-controlled discontinuation study. Davidson, JR., Connor, KM., Hertzberg, MA., et al.[2019]

Fluoxetine has been shown to be an effective treatment for post-traumatic stress disorder (PTSD) based on a meta-analysis of 7 randomized controlled trials, indicating a relative risk of response of 1.21.

The medication is associated with only mild adverse effects, making it a safer option for individuals suffering from PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine as a treatment for post-traumatic stress disorder. Xu, JJ., Chan, MJ., Yang, YC.[2013]

In a study of 144 veterans with combat-related PTSD, fluoxetine (20-80 mg) showed significantly greater improvements in PTSD symptoms compared to placebo during both the acute treatment phase and the maintenance phase, with notable reductions in PTSD-specific scores.

Fluoxetine was well tolerated at an average dose of 65 mg, and it effectively reduced the risk of relapse compared to placebo, indicating its potential as a reliable long-term treatment for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine in the acute treatment and relapse prevention of combat-related post-traumatic stress disorder: Analysis of the veteran group of a placebo-controlled, randomized clinical trial. Martenyi, F., Soldatenkova, V.[2014]

Fluoxetine has demonstrated antidepressant efficacy in major depression and may also be effective for a variety of other psychiatric conditions, including obsessive-compulsive disorder, anorexia nervosa, and Tourette's syndrome.

The pharmacological profile of fluoxetine suggests potential applications beyond depression, such as pain relief in diabetics and management of conditions like premenstrual syndrome and migraine headaches, although further controlled studies are needed to confirm these uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine: a spectrum of clinical applications and postulates of underlying mechanisms. Messiha, FS.[2019]

In a 12-week trial involving 411 patients with posttraumatic stress disorder, fluoxetine at both 20 mg and 40 mg doses did not show a significant difference in effectiveness compared to placebo.

The study revealed a notably higher placebo response rate than in previous trials, suggesting that the perceived benefits of treatment may be influenced by psychological factors rather than the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failed efficacy of fluoxetine in the treatment of posttraumatic stress disorder: results of a fixed-dose, placebo-controlled study. Martenyi, F., Brown, EB., Caldwell, CD.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Maintenance therapy with fluoxetine in posttraumatic stress disorder: a placebo-controlled discontinuation study. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of fluoxetine on the 5-HT1A receptor and recovery of cognitive function after traumatic brain injury in rats. [2022]

3. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Fluoxetine as a treatment for post-traumatic stress disorder. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fluoxetine in the acute treatment and relapse prevention of combat-related post-traumatic stress disorder: Analysis of the veteran group of a placebo-controlled, randomized clinical trial. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Evaluation of suicidality during pharmacologic treatment of mood and nonmood disorders. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Evaluating suicide-related adverse events in clinical trials of fluoxetine treatment in adults for indications other than major depressive disorder. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Fluoxetine: a suitable long-term treatment. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Fluoxetine treatment in poststroke depression, emotional incontinence, and anger proneness: a double-blind, placebo-controlled study. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of social stress and fluoxetine treatment on fracture healing in a rat femur fracture model. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Fluoxetine: a spectrum of clinical applications and postulates of underlying mechanisms. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Failed efficacy of fluoxetine in the treatment of posttraumatic stress disorder: results of a fixed-dose, placebo-controlled study. [2013]