Fluoxetine for PTSD

Recruiting at 11 trial locations

Overseen By Please visit the website:

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Global Coalition for Adaptive Research

Must not be taking: Fluoxetine

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: 2

Duration: 12 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of fluoxetine, a medication commonly used for depression, in treating PTSD (post-traumatic stress disorder). The study compares fluoxetine to a placebo (a pill with no active ingredient) to evaluate its impact on PTSD symptoms. Individuals who have not taken fluoxetine for PTSD at a dose of 20 mg daily for at least four weeks may be suitable candidates. The trial aims to determine if fluoxetine can serve as a safe and effective treatment for managing PTSD symptoms. As a Phase 2 trial, this research measures fluoxetine's effectiveness for PTSD in an initial, smaller group, offering participants the opportunity to contribute to significant treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have been recently treated for PTSD with fluoxetine at 20 mg daily for at least 4 weeks, you may not be eligible to participate.

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

Research has shown that fluoxetine is generally well-tolerated for treating post-traumatic stress disorder (PTSD). In studies, patients using fluoxetine experienced lasting improvements and found it helpful during treatment. However, like many medications, fluoxetine might cause some side effects. One review found a slightly higher chance of side effects compared to a placebo. Some people might experience issues like nausea or headaches, but these are often mild. Discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for PTSD, which often include psychotherapy and medications like sertraline and paroxetine, fluoxetine offers a unique approach by targeting serotonin reuptake more selectively. Researchers are excited about fluoxetine because it has a well-established safety profile, being widely used as an antidepressant, and it may provide an effective alternative for individuals who don't respond well to current PTSD medications. Additionally, fluoxetine's potential to alleviate PTSD symptoms with fewer side effects compared to other medications makes it a promising candidate for improving patient outcomes.

What evidence suggests that fluoxetine might be an effective treatment for PTSD?

Research has shown that fluoxetine, which participants in this trial may receive, can effectively treat PTSD. In one study, by Week 5, fluoxetine significantly reduced PTSD symptoms compared to a placebo, as measured by a clinical scale. Another study found that fluoxetine not only helped people with PTSD but was also well-tolerated with mild side effects. Additionally, fluoxetine provided lasting improvement for those with combat-related PTSD. These findings suggest fluoxetine can be a promising option for managing PTSD symptoms. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with PTSD who haven't been treated with fluoxetine (20 mg daily) for at least 4 weeks recently. If they've used fluoxetine before for other reasons, they might still qualify but will need to discuss this with the study's medical monitor.

Inclusion Criteria

No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT05422612)

Exclusion Criteria

I have taken fluoxetine in the past for reasons other than PTSD.

I have been treated for PTSD with fluoxetine 20 mg daily for at least 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive fluoxetine or placebo for the treatment of PTSD

12 weeks

Regular visits (frequency not specified)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Fluoxetine

Trial Overview The study is testing Fluoxetine Hydrochloride's safety and effectiveness in treating PTSD compared to a placebo. It's a Phase 2 trial where participants are randomly assigned to either the medication or placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Intervention A: Fluoxetine HCl Experimental Treatment 1 Intervention

Group II: Intervention A Placebo Placebo Group 1 Intervention

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?

Global Coalition for Adaptive Research

Lead Sponsor

Trials

7

Recruited

22,600+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

Citeline

Industry Sponsor

Trials

5

Recruited

1,600+

PPD Development, LP

Industry Sponsor

Idorsia Pharmaceuticals Ltd.

Industry Sponsor

Trials

124

Recruited

36,400+

Antonio Olivieri

Idorsia Pharmaceuticals Ltd.

Chief Medical Officer since 2024

Not specified

André C. Muller

Idorsia Pharmaceuticals Ltd.

Chief Executive Officer

Not specified

Citeline

Collaborator

Trials

5

Recruited

1,600+

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Berry Consultants

Collaborator

Trials

16

Recruited

58,200+

Cambridge Cognition Ltd

Industry Sponsor

Trials

17

Recruited

4,700+

Published Research Related to This Trial

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 10-week trial involving 27 patients with combat-related PTSD, fluoxetine significantly reduced PTSD symptoms, with total Clinician-Administered PTSD Scale scores dropping from 64.5 to 42.7, indicating effective symptom management across all subscales.

Fluoxetine also led to a notable decrease in panic attack frequency for some patients, suggesting its potential benefits beyond just PTSD symptoms, although the study highlighted a high dropout rate due to side effects and other factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open prospective trial of fluoxetine for posttraumatic stress disorder. Nagy, LM., Morgan, CA., Southwick, SM., et al.[2013]

A systematic review of 21 studies found that fluoxetine use during the first trimester of pregnancy does not significantly increase the risk of major fetal malformations, with an odds ratio of 1.12, indicating safety for the fetus.

However, there is a noted increased risk of cardiac malformations associated with fluoxetine use, with an odds ratio of 1.6 from cohort studies, suggesting that this risk may be influenced by factors such as ascertainment bias in reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fetal safety of fluoxetine: a systematic review and meta-analysis. Riggin, L., Frankel, Z., Moretti, M., et al.[2022]

In a study of 65 PTSD patients over 12 weeks, fluoxetine was well-tolerated, with only one patient discontinuing due to side effects, indicating its safety for this population.

The most common treatment-emergent symptoms associated with fluoxetine were mild (nausea, diarrhea, and thirst), and there were no significant activating effects, suggesting fluoxetine is a viable treatment option for PTSD without major tolerability concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of fluoxetine in posttraumatic stress disorder. Barnett, SD., Tharwani, HM., Hertzberg, MA., et al.[2022]

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, a widely prescribed antidepressant since 1988, is known for its mechanism as a serotonin reuptake inhibitor, which helps improve mood in patients with depression.

Despite its reputation for safety, recent literature has highlighted various adverse effects and drug interactions associated with fluoxetine, emphasizing the need for healthcare professionals to be aware of these issues to prevent complications in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects and drug interactions associated with fluoxetine therapy. Levinson, ML., Lipsy, RJ., Fuller, DK.[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]

In a study of 6,839 VA outpatients with PTSD, no significant differences in medication efficacy were found among fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine, suggesting that these medications are similarly effective in real-world settings.

Patients with higher baseline PTSD checklist scores and those receiving evidence-based psychotherapy showed better improvement, while those with high disability levels were less likely to experience meaningful benefits, highlighting the importance of combined treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient and Clinical Factors Associated With Response to Medications for Posttraumatic Stress Disorder. Shiner, BR., Gui, J., Rozema, L., et al.[2022]

In a study of 106 cases of acute fluoxetine overdose, nearly half (48.6%) of patients who ingested fluoxetine alone remained asymptomatic, suggesting a relatively low toxicity profile for the drug in overdose situations.

Among those who did show symptoms, common issues included sleepiness and mild heart rate increases, indicating that while fluoxetine overdose can lead to some effects, it is generally considered to be benign compared to other overdoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fluoxetine in the overdose patient. Borys, DJ., Setzer, SC., Ling, LJ., et al.[2019]

Fluoxetine is generally safe and well-tolerated for treating depression and other neuropsychiatric disorders, with common side effects primarily affecting the gastrointestinal and nervous systems at the recommended dose of 20 mg/day.

Its long half-life reduces the risk of withdrawal symptoms, but fluoxetine can interact with other medications due to its inhibition of certain liver enzymes, although most interactions are not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and side effect profile of fluoxetine. Wernicke, JF.[2022]

Citations

1. 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) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21677618/

Fluoxetine as a Treatment for Post-Traumatic Stress Disorder Findings suggest that fluoxetine is an effective treatment for PTSD, with mild adverse effects on individuals.

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

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

4. ptsd.va.gov ptsd.va.gov/professional/articles/article-pdf/id41029.pdf

Meta-Analysis of the Efficacy of Treatments for ... A resilience-oriented treatment for posttraumatic stress disorder: results of a preliminary randomized clinical trial. J Trauma Stress. 2011 ...

5. nature.com nature.com/articles/s41398-017-0014-5

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. Lior Ariel,; Sapir Inbar ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8725683/

Pharmacological therapy for post-traumatic stress disorder We completed a review of pharmacological monotherapy in 2015 which found that paroxetine, fluoxetine, sertraline and venlafaxine could be effective for PTSD, ...

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00559/full

Comparative Efficacy and Acceptability of Pharmaceutical ... Nevertheless, in terms of safety, medicine interventions indicated a higher risk of adverse effect compared with placebo (RR = 1.47, 95% CI: 1.24 to 1.75).

8. mentalhealth.bmj.com mentalhealth.bmj.com/content/6/2/51.full

Fluoxetine may prevent relapse in post traumatic stress ... After 12 weeks of acute treatment with fluoxetine, responders received 24 weeks of relapse prevention with fluoxetine or placebo. (Responders ...