Fluoxetine for PTSD

Recruiting at 7 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

Trial Summary

What is the purpose of this trial?

This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD utilizing an adaptive platform trial design. Intervention A - Fluoxetine will assess the safety and efficacy of fluoxetine in participants with PTSD. Please see NCT05422612 for information on the S-21-02 Master Protocol.

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.

What data supports the effectiveness of the drug fluoxetine for treating PTSD?

Research shows that fluoxetine can be effective for PTSD, as one study found it led to greater improvements in PTSD symptoms compared to a placebo, and another study showed lower relapse rates with fluoxetine. However, another study did not find a significant difference between fluoxetine and placebo, indicating mixed results. ^{1 2 3 4 5}

Is fluoxetine generally safe for humans?

Fluoxetine, also known as Prozac, is generally considered safe and well-tolerated for humans. Common side effects include issues with the stomach and nervous system, and it can interact with other drugs, but most interactions are not serious. In cases of overdose, it appears to be relatively benign with minimal risk of serious complications. ^{6 7 8 9 10}

How does the drug fluoxetine differ from other treatments for PTSD?

Fluoxetine, commonly known as Prozac, is unique for PTSD treatment as it has been shown to significantly reduce symptoms in combat-related PTSD and prevent relapse better than a placebo. It is a selective serotonin reuptake inhibitor (SSRI), which works by increasing serotonin levels in the brain, a different mechanism compared to other PTSD medications like topiramate or venlafaxine. ^{1 2 4 5 11}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

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+

Findings from Research

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 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 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]

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]

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 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]

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 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]

References

1. 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]

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

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

3. 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]

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

Open prospective trial of fluoxetine for posttraumatic stress disorder. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Tolerability of fluoxetine in posttraumatic stress disorder. [2022]

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

The fetal safety of fluoxetine: a systematic review and meta-analysis. [2022]

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

The effects of fluoxetine in the overdose patient. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Safety and side effect profile of fluoxetine. [2022]

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

Adverse effects and drug interactions associated with fluoxetine therapy. [2019]

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

Patient and Clinical Factors Associated With Response to Medications for Posttraumatic Stress Disorder. [2022]