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

Trial Summary

What is the purpose of this trial?

This trial tests whether using Fluoxetine soon after an injury can prevent or reduce PTSD and depression in people who have been physically hurt. The medication works by boosting a 'feel-good' chemical in the brain to help improve mood and reduce anxiety. Fluoxetine is an antidepressant that has been shown to be effective in treating PTSD.

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 data supports the effectiveness of the drug fluoxetine for bodily trauma recovery?

While fluoxetine did not show effectiveness in one study for posttraumatic stress disorder (PTSD), another study found that it helped prevent relapse in PTSD patients, with a lower relapse rate compared to placebo. Additionally, fluoxetine showed greater improvements in PTSD symptoms in veterans compared to placebo in another trial. ^{1 2 3 4 5}

Is fluoxetine generally safe for humans?

Fluoxetine is generally considered safe for humans, with studies showing it is well-tolerated and has a favorable safety profile compared to older antidepressants. It has been used safely in various conditions, including depression, PTSD, and bulimia, and is not associated with an increased risk of serious complications in overdose cases. ^{1 2 3 6 7}

How does the drug fluoxetine differ from other treatments for bodily trauma recovery?

Fluoxetine, commonly known as Prozac, is unique in its potential neuroprotective effects and anti-inflammatory properties, which may aid in recovery from bodily trauma by protecting the brain after events like cardiac arrest. This is different from other treatments that may not target these specific mechanisms. ^{1 2 3 8 9}

Research Team

Jennifer Hagan, MD

Principal Investigator

University of Florida

Eligibility Criteria

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

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

Treatment Details

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.

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 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+

Findings from Research

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 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 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 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]

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]

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]

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]

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]

References

1. 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]

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

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

3. 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]

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

Fluoxetine in posttraumatic stress disorder. [2013]

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

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

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

Fluoxetine: a review on evidence based medicine. [2020]

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

Fluoxetine ingestion: a one year retrospective study. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Fluoxetine has neuroprotective effects after cardiac arrest and cardiopulmonary resuscitation in mouse. [2022]

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

Basolateral Amygdala but Not Medial Prefrontal Cortex Contributes to Chronic Fluoxetine Treatments for PTSD Symptoms in Mice. [2021]