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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether fluoxetine, a medication commonly used for depression, can improve mental health in individuals recovering from serious bone injuries. Such injuries often lead to ongoing mental health issues like anxiety and depression. Participants will be randomly assigned to receive either fluoxetine or a calcium supplement to determine which is more effective at improving mental health. The study seeks adults who require surgery for bone fractures in their arms, legs, or pelvis and are being treated at UF Health. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important mental health advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fluoxetine, a common antidepressant, is generally safe for people with post-traumatic stress disorder (PTSD). Studies indicate that most patients tolerate it well, meaning it usually doesn't cause serious side effects. For example, one study found that patients with PTSD did not experience major side effects that can sometimes occur with antidepressants. Another study demonstrated that fluoxetine is effective and well-tolerated for treating PTSD related to combat. While individual reactions can vary, the evidence suggests fluoxetine is a safe option for managing mental health symptoms after traumatic events. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for mental health in musculoskeletal injuries?

Unlike the standard treatments for post-traumatic mental health issues, which often include psychotherapy and medications like selective serotonin reuptake inhibitors (SSRIs) such as sertraline or paroxetine, fluoxetine offers a unique approach. Fluoxetine, another type of SSRI, is being explored for its potential benefits in patients with musculoskeletal injuries. Researchers are excited about fluoxetine because it might help manage the psychological stress associated with these injuries while also being well-tolerated. By targeting serotonin levels in the brain, fluoxetine could provide a dual benefit—addressing both mental health and the physical recovery process, which is an area current treatments haven't fully explored.

What evidence suggests that this trial's treatments could be effective for post-traumatic mental health in musculoskeletal injuries?

Research shows that fluoxetine, which participants in this trial may receive, can improve mental health after trauma. Studies have found that it reduces symptoms of depression and anxiety in people with post-traumatic stress disorder (PTSD). Specifically, by the fifth week of treatment, fluoxetine significantly lowered overall PTSD symptoms compared to a placebo. A review of seven studies confirmed its effectiveness in treating PTSD. Therefore, for those facing mental health challenges after a musculoskeletal injury, fluoxetine might provide some relief. Another group in this trial will receive calcium supplementation as a comparator. ^{3 6 7 8 9}

Who Is on the Research Team?

Jennifer Hagen, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9382753/

Can fluoxetine mitigate mental health decline in ... ° Hypothesis: patients randomized to fluoxetine will have less severe depression, anxiety, and post-traumatic stress symptoms, and improved self ...

2. pilotfeasibilitystudies.biomedcentral.com pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-022-01119-8

Can fluoxetine mitigate mental health decline in ... ° Hypothesis: patients randomized to fluoxetine will have less severe depression, anxiety, and post-traumatic stress symptoms, and improved self ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/7814344/

Fluoxetine in posttraumatic stress disorder Results: By Week 5 fluoxetine, but not placebo, significantly reduced overall PTSD symptomatology, as assessed by the Clinician-Administered PTSD Scale (CAPS) ...

4. withpower.com withpower.com/trial/early-phase-1-8-2021-f4cce

Fluoxetine for Post-Traumatic Mental Health in ... 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, ...

5. researchgate.net researchgate.net/publication/362748029_Can_fluoxetine_mitigate_mental_health_decline_in_musculoskeletal_trauma_patients_a_pilot_single-center_randomized_clinical_trial

(PDF) Can fluoxetine mitigate mental health decline in ... More than 50% of victims of musculoskeletal trauma suffer lasting mental health issues and post-traumatic stress disorder (PTSD) symptomology following their ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12171264/

Pharmacotherapy for post-traumatic stress disorder This meta-analysis supports antidepressants and antipsychotics have no significant difference in improving clinical symptoms and acceptabity, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584601002822

Tolerability of fluoxetine in posttraumatic stress disorder This systematic assessment of TES indicated that PTSD patients tolerated fluoxetine well without pronounced activating side effects.

8. ptsd.va.gov ptsd.va.gov/professional/treat/txessentials/clinician_guide_meds.asp

Clinician's Guide to Medications for PTSD The 2023 VA/DoD CPG recommends 2 SSRIs (sertraline and paroxetine) as having the most robust empirical evidence for reducing PTSD symptoms in randomized ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924977X05001781

Fluoxetine in the acute treatment and relapse prevention of ... Fluoxetine is effective and well-tolerated in acute treatment of combat-related PTSD. It provides sustained improvement during extended maintenance treatment ...