Fluoxetine for Bodily Trauma Recovery

Overseen By MaryBeth Horodyski, EdD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Florida

Must not be taking: SSRIs

Disqualifiers: Severe TBI, Incarceration, Pregnancy, 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

Compensation: Varies

Number of Visits: 14

Duration: 9 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Fluoxetine can aid recovery after serious physical injuries. Researchers aim to determine if taking Fluoxetine soon after an injury reduces the risk of developing mental health issues like PTSD and depression, as well as lowers pain levels and the need for opioids. Participants will be randomly assigned to receive either Fluoxetine or a placebo (a pill with no active medicine) during their hospital stay. The trial seeks individuals admitted to UF Health with severe injuries, such as broken bones requiring surgery or chest injuries needing an operation. As a Phase 4 trial, Fluoxetine is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are currently on an SSRI (a type of antidepressant), you cannot participate in the trial.

What is the safety track record for Fluoxetine and Placebo?

Research shows that fluoxetine is generally well-tolerated by patients. In a study with 123 people who had posttraumatic stress disorder (PTSD), fluoxetine significantly reduced the recurrence of PTSD symptoms from 50% to 22%. This suggests it may help improve mental health after trauma.

However, studies have also identified some risks. Fluoxetine increased the chances of seizures, falls with injury, and bone fractures in some patients. Despite these risks, it effectively reduced symptoms of depression, which is one of the main reasons for using fluoxetine.

Overall, fluoxetine has been safely used for many years to treat various conditions. While some side effects are possible, the mental health benefits might outweigh these for many people. Always consult medical professionals to determine if it's the right choice. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using fluoxetine for bodily trauma recovery because it offers a novel approach compared to traditional pain management and physical therapy. Unlike standard treatments that primarily focus on physical rehabilitation and pain relief, fluoxetine, commonly known as an antidepressant, may aid recovery by influencing serotonin levels, which could improve mood and reduce stress. This unique mechanism of action might enhance the overall recovery process by addressing both the physical and psychological aspects of trauma recovery.

What evidence suggests that Fluoxetine might be an effective treatment for bodily trauma recovery?

Research shows that fluoxetine, which participants in this trial may receive, can help reduce symptoms of PTSD and depression in people who have experienced trauma. In a study with 123 people who had PTSD, those taking fluoxetine were less likely to experience a return of symptoms, with a relapse rate of 22% compared to 50% for those not taking it. Other studies suggest that fluoxetine may also help reduce depression, anxiety, and PTSD symptoms. Although some research did not find it helpful for stroke recovery, fluoxetine's success in mental health makes it a promising option for preventing negative mental health symptoms after physical trauma. ^{1 2 3 5 6}

Who Is on the Research Team?

Jennifer Hagan, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for trauma patients at UF Health with injuries like fractures needing surgery, pelvic or chest/abdominal injuries requiring OR intervention, polytrauma, or those feeling moderately depressed (BDI-II ≥ 14). It's not for those with severe brain injury, pregnant/in jail individuals, people who can't consent due to language/cognitive barriers, on SSRI treatment for other psychiatric conditions, unlikely to survive past 90 days or with a history of substance abuse.

Inclusion Criteria

You have multiple injuries affecting different parts of your body or you have severe depression according to a specific questionnaire.

I need surgery for one or more broken bones in my arms or legs.

I have had a pelvic fracture.

Exclusion Criteria

Severe Traumatic Brain Injury or cognitively not able to participate in surveys (Glasgow Coma Scale 3-8)

Incarceration or Pregnancy

Unable to provide informed consent due to language or other barriers

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Fluoxetine or placebo starting at their index hospitalization, with dosage adjustments over 9 months

9 months

Visits at 2 weeks, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pain and depression

3 months

Final follow-up visit at 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Fluoxetine
• Placebo

Trial Overview The study tests if Fluoxetine given right after bodily trauma can help prevent PTSD and depression. It also looks at whether it reduces pain and the need for opioids without changing usual pain treatments. Participants are randomly assigned to get either Fluoxetine or a placebo during their initial hospital stay.

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 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

Group II: Subjects randomized to Placebo Active Control 1 Intervention

When a patient is enrolled, the inpatient research pharmacy will dispense the appropriately randomized medication in a visually similar, over-encapsulated form as Fluoxetine

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 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]

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]

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 study involving male mice subjected to cardiac arrest and resuscitation, a high dose of fluoxetine (10 mg/kg) was found to protect neurons in the caudate putamen and reduce sensorimotor deficits when administered after global cerebral ischaemia.

The lower dose of fluoxetine (5 mg/kg) did not provide protective effects, indicating that the efficacy of fluoxetine in reducing neuronal damage may depend on the dosage used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine has neuroprotective effects after cardiac arrest and cardiopulmonary resuscitation in mouse. Taguchi, N., Nakayama, S., Tanaka, M.[2022]

In a 5-week study involving 64 participants with PTSD, fluoxetine significantly reduced overall PTSD symptoms compared to placebo, particularly in arousal and numbing symptoms.

Fluoxetine was found to be an effective treatment for PTSD, especially in non-veteran patients, and demonstrated antidepressant effects regardless of its impact on PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine in posttraumatic stress disorder. van der Kolk, BA., Dreyfuss, D., Michaels, M., et al.[2013]

Chronic fluoxetine treatment significantly reduced fear and depression symptoms in mice subjected to footshock-induced PTSD, indicating its efficacy in alleviating PTSD-related behaviors.

The study found that while fluoxetine treatment decreased c-Fos expression in the basolateral amygdala (BLA), it did not affect the medial prefrontal cortex (mPFC) areas, suggesting that the BLA plays a key role in the mechanism by which fluoxetine alleviates PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basolateral Amygdala but Not Medial Prefrontal Cortex Contributes to Chronic Fluoxetine Treatments for PTSD Symptoms in Mice. Yu, YH., Ou, CY., Shyu, BC., et al.[2021]

Fluoxetine is proven to be safe and effective for treating depression, showing benefits from the first week of therapy in a review of 9087 patients across 87 clinical trials.

It has a favorable safety profile compared to older antidepressants, leading to lower dropout rates and better patient compliance, and is also effective in treating conditions like bulimia nervosa and OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine: a review on evidence based medicine. Rossi, A., Barraco, A., Donda, P.[2020]

A retrospective review of 44 fluoxetine exposure cases over one year found that overdose presents minimal risk of serious cardiovascular or neurological complications, with most cases being asymptomatic or experiencing mild symptoms.

Among the cases reviewed, no seizures were recorded, and adverse reactions were primarily linked to coingestants rather than fluoxetine itself, suggesting that fluoxetine is relatively safe even in overdose situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine ingestion: a one year retrospective study. Spiller, HA., Morse, S., Muir, C.[2022]

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

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Can fluoxetine mitigate mental health decline in ... This is a single-center, repeated measures, randomized controlled pilot study including up to 100 orthopedic trauma patients aged between 18 and 85 years of ...

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Fluoxetine for Bodily Trauma Recovery In a one-year trial involving 123 subjects with posttraumatic stress disorder, fluoxetine (FLU) significantly reduced relapse rates to 22% compared to 50% for ...

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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 ...

4. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.120.033070

Twelve-Month Outcomes of the AFFINITY Trial ... Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 ...

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Fluoxetine treatment is effective in a rat model of childhood ... Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder | Translational Psychiatry.

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Individual patient data meta-analysis of the effects of ... Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression ...