Atomoxetine for PTSD

Overseen By Mark B Hamner, MD BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: Psycho-stimulants, MAOIs, SSRIs, others

Disqualifiers: Glaucoma, Hypertension, Epilepsy, TBI, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if atomoxetine, a medication typically used for ADHD, can enhance attention and executive function (mental skills for managing tasks) in veterans with PTSD. Many individuals with PTSD also experience attention deficits, which can worsen symptoms and impede recovery. Participants will take either the active medication or a placebo (a pill with no active ingredients) for 12 weeks to assess improvements in quality of life and social function. Veterans with PTSD and attention deficits who are in good physical health may be suitable candidates for this study. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that could interact with atomoxetine, such as monoamine oxidase inhibitors (MAOIs), antihypertensive medications, and some antidepressants like paroxetine, venlafaxine, and fluoxetine. If you are on psycho-stimulants or other similar medications, you must stop them at least 2 weeks before starting the trial. However, you can continue with approved standard therapies if your PTSD symptoms are still severe enough to meet the trial's criteria.

What is the safety track record for atomoxetine?

Research has shown that atomoxetine, a non-stimulant medication, is generally safe for individuals with ADHD and PTSD. The FDA has already approved it for treating ADHD, which supports its safety profile. Previous studies found that atomoxetine reduced ADHD symptoms and improved the quality of life for Veterans with both ADHD and PTSD.

Although detailed information on long-term effects is limited, available data suggest that atomoxetine is well-tolerated. Unlike stimulant medications, it is not addictive, which benefits those with PTSD. Some studies note that safety information is limited and results can vary, but overall, the treatment appears promising for improving attention issues related to PTSD. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for PTSD, which often include psychotherapy and medications like SSRIs or SNRIs, atomoxetine offers a unique approach by targeting norepinephrine reuptake in the brain. This mechanism is different from the common serotonin-focused strategies, potentially providing an alternative for those who don't respond well to existing medications. Researchers are excited about atomoxetine because it might address PTSD symptoms through this novel pathway, offering hope for improved outcomes in patients who have limited success with current options.

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

Research has shown that Atomoxetine (ATX), a non-stimulant medication, might help individuals with both ADHD and PTSD. Studies have found that ATX can slightly reduce ADHD symptoms, which often overlap with PTSD symptoms. Evidence indicates that ATX can improve executive function, including mental skills needed for managing tasks and focusing, in individuals with PTSD. Additionally, ATX has been reported to help with chronic pain in some PTSD patients, potentially leading to a better overall quality of life. While ATX may not affect all PTSD symptoms, its ability to improve attention and executive function makes it a promising treatment option. In this trial, participants will receive either active Atomoxetine or a placebo to evaluate its effectiveness specifically for PTSD. ^{1 2 4 6 7}

Who Is on the Research Team?

Zhewu Wang, MD

Principal Investigator

Ralph H. Johnson VA Medical Center, Charleston, SC

Are You a Good Fit for This Trial?

This trial is for veterans with PTSD who also have attention deficits and executive function difficulties. Participants should not be fully responsive to conventional PTSD treatments and are looking for new strategies to improve their quality of life and social functioning.

Inclusion Criteria

I am between 65 and 75 years old, meeting the specific age criteria.

ADHD has been recognized as a neurobehavioral impairment in executive function (Brown, 2008)

I am a veteran aged 18-75 with PTSD and AD, meeting the required CAPS and CAARS-S:S scores.

Exclusion Criteria

Known sensitivity to ATX

An active or lifetime major mental health diagnosis as determined by DSM-5 major psychiatric disorders, including schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified, bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise specified, the project will allow the presence of depressive disorders if the depressive episodes are secondary to PTSD

I stopped taking psycho-stimulants or SSRIs at least 2 weeks before the trial starts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive atomoxetine or placebo for 12 weeks to assess improvement in executive function and attention

12 weeks

4 visits (in-person), weekly phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (virtual or in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Atomoxetine

Trial Overview The study tests Atomoxetine (ATX), a non-stimulant medication approved for ADHD, on improving attention and executive functions in individuals with PTSD. It's a double-blind trial, meaning neither the researchers nor participants know who gets ATX or placebo during the 12-week treatment period.

How Is the Trial Designed?

Group I: active atomoxetine Experimental Treatment 1 Intervention

Active ATX (40mg capsules) will be prepared. Initial dose is 40mg, titrated to 80mg if tolerable in one week.

Group II: Placebo Placebo Group 1 Intervention

placebo pill appears like real atomoxetine pill but has no therapeutic ingredient and benefit. The same schedule to distribution as Atomoxetine arm.

Atomoxetine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Strattera for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in European Union as Strattera for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in Canada as Strattera for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

A case of a 17-year-old girl who overdosed on 2840 mg of atomoxetine resulted in a seizure and mild cardiac issues, highlighting the potential risks associated with high doses of this medication.

Despite the overdose, the patient showed significant improvement within 24 hours, indicating that while atomoxetine can cause serious effects in overdose situations, recovery is possible with appropriate medical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolated atomoxetine overdose resulting in seizure. Kashani, J., Ruha, AM.[2015]

Atomoxetine is an effective non-stimulant treatment for ADHD in children and adolescents, showing significant improvements in ADHD symptoms compared to placebo across six clinical trials involving over 3,000 participants.

The drug is well tolerated with minimal side effects, primarily gastrointestinal issues and decreased appetite, and it does not appear to have abuse potential, making it a safe long-term option for managing ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atomoxetine (Strattera), an alternative in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children]. Gaillez, C., Sorbara, F., Perrin, E.[2020]

Atomoxetine (Strattera) is an effective nonstimulant treatment for adults with ADHD, showing greater symptom improvement compared to placebo in two large 10-week trials, with mean reductions in ADHD symptoms of 28.3% to 30.1%.

Atomoxetine is generally well tolerated, with a low risk of abuse or diversion, making it a suitable option for patients who may be at risk for substance abuse; it is not a controlled substance in the US.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder. Simpson, D., Plosker, GL.[2018]

Atomoxetine significantly reduces ADHD symptoms in children and adolescents, especially in those with co-existing conditions like anxiety and depression, with a number needed to treat of 3.4-5.

While most side effects are mild and temporary, serious risks include increased vascular tone, decreased growth rate, and heightened suicidal behavior, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atomoxetine for treatment of children and adolescents with ADHD]. Resen, K., Pagsberg, AK., Jörgens, G.[2017]

In a safety analysis of 15 clinical trials involving 4829 adults with ADHD, atomoxetine was associated with a higher rate of treatment-emergent adverse events compared to placebo (81.3% vs. 68.3% for acute trials), but no new adverse events were identified, confirming its known safety profile.

Atomoxetine led to modest increases in heart rate and blood pressure, but there was no increased risk of serious adverse events or suicidal ideation, indicating it is a safe treatment option for adults with ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of atomoxetine in treatment of attention deficit hyperactivity disorder in adult patients: an integrated analysis of 15 clinical trials. Camporeale, A., Porsdal, V., De Bruyckere, K., et al.[2015]

Atomoxetine, a nonstimulant medication approved for ADHD, works as a selective norepinephrine reuptake inhibitor and is structurally related to fluoxetine, an antidepressant.

While common side effects include gastrointestinal disturbances, this case highlights potential cardiovascular issues such as syncope, orthostatic hypotension, and tachycardia, which may arise from increased noradrenergic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular side effects of atomoxetine and its interactions with inhibitors of the cytochrome p450 system. Kasi, PM., Mounzer, R., Gleeson, GH.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35312136/

Atomoxetine in comorbid ADHD/PTSD: A randomized, ... Atomoxetine demonstrated modest efficacy for ADHD symptoms; quality of life measures and PTSD symptoms were not affected.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06573970/atomoxetine-and-executive-function-in-ptsd

Atomoxetine and Executive Function in PTSD The proposed study directly addresses this knowledge gap by testing the efficacy of atomoxetine (ATX) in improving EF and attention among Veterans with PTSD.

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1221694/full

Case report: Atomoxetine improves chronic pain with ... The study showed that chronic pain with PTSD may be comorbid with ADHD. Moreover, we found that ATX can improve chronic pain with PTSD and cerebral blood flow.

4. withpower.com withpower.com/trial/phase-4-stress-disorders-post-traumatic-11-2024-cfcef

Atomoxetine for PTSD · Info for Participants Additionally, a study suggests that Atomoxetine may be safe and effective for people with both ADHD and PTSD, indicating potential benefits for PTSD treatment.

5. grantome.com grantome.com/grant/NIH/I21-RX001725-01

Atomoxetine in Comorbid ADHD/PTSD: A Pilot, Placebo ... Treatment with methylphenidate showed improvement in their academic and occupational performance, and improvement in the PTSD treatment outcome in patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06573970?aggFilters=status%3Anot%2Cphase%3A

Atomoxetine and Executive Function in PTSD An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12579877/

Pharmacological Management of Post-Traumatic Stress ... ... Results were inconsistent, often limited by small samples. Safety data were sparse; long-term effects are rarely reported. Full details for ...