RecruitingPhase 4

Atomoxetine and Executive Function in PTSD

United States160 participantsStarted 2026-04-01

Plain-language summary

Attention deficits (AD) frequently co-occur with posttraumatic stress disorder (PTSD). The presence of AD is associated with greater PTSD clinical severity and poorer clinical outcomes. Knowledge regarding the mechanism underlying this association is limited, though the emerging evidence has indicated that executive function deficit (EFD) is strongly correlated with AD and PTSD symptoms. While treatments developed for PTSD have existed for years, a substantial portion of individuals do not fully respond to conventional treatment. Accumulating evidence suggest that attention deficit (AD) and EFD may be a driving force for PTSD treatment resistance. However, treatment of executive impairment in PTSD is very limited. As a result, untreated co-occurring AD and EFD in PTSD poses severe negative impacts on patients' functional recovery, treatment outcomes, and quality of life (QoL). Given that up to 50% of patients do not respond well to the first-line pharmacological PTSD treatments, it is imperative to seek novel treatment strategies to improve EF that may improve both standard treatment response and QoL, social function. The proposed study directly addresses this knowledge gap by testing the efficacy of atomoxetine (ATX) in improving EF and attention among Veterans with PTSD, which will further improve Veterans' QoL and social function. ATX represents a promising novel candidate pharmacotherapy for individuals with PTSD. ATX is a non-stimulant selective norepinephrine reuptake inhibitor (SNRI), approved by the FDA for the treatment of ADHD. Studies suggest that ATX, unlike stimulants, lacks addictive properties and shows efficacy in the treatment of comorbid depression and anxiety, which is ideal in the treatment of PTSD. Data from the investigators' preliminary study provides encouraging support for the therapeutic potential of ATX in improving EF in Veterans with comorbid PTSD/ADHD. The investigators' recent research uncovered a higher rate of ADHD among Veterans with PTSD, and the comorbid AD symptoms were correlated with PTSD severity and poorer treatment outcomes. Treatment with ATX showed significant symptoms reduction in ADHD and improvement in inhibitory function in Veterans with ADHD/PTSD. In the proposed study, the investigators will focus on ATX in improvement of EF and attention, and further psycho-social life function and QoL. The investigators will (1) employ a randomized, double-blind design that will consist of 12 weeks of treatment with ATX or placebo medication; (2) use standardized, repeated dependent measures to rigorously assess AD and EFD symptomatology; (3) measure impairment in associated mental and behavioral health problems (e.g., attention deficit, depression, anxiety, suicidality, QoL, family/social functioning); and (4) use response inhibition task GoNogo, working memory and attention tests Digit Span and Trail Making to investigate the underlying pathophysiology of PTSD and prognostic indicators of treatment outcome. To achieve these goals, the investigators have assembled a multidisciplinary team with expertise in PTSD, ADHD clinical trials, and human laboratory paradigms who have successfully collaborated in the past and are uniquely qualified to implement this type of investigation. The proposed project is directly responsive to the mission of the VA-RRD "to maximize Veterans' functional independence, quality of life and participation in their lives and community." Successful completion of this study will provide a platform for a large multi-center trial to further confirm the important role of EF in PTSD treatment outcomes. The findings from this study will provide critically needed evidence to help inform clinical practice guidelines on the treatment of PTSD. The outcome of the proposed research will be significant, because it provides a knowledge base to allow for development of new PTSD intervention strategies. More importantly, this clinical trial may immediately benefit Veterans by enhancing their cognitive function, reducing AD related disability, and further improving quality of life for Veterans who suffer from PTSD.

Who can participate

Age range

18 Years – 75 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Veterans ages 18 to 75 with PTSD and AD (CAPS \> 35 for age 18 to 64, CAPS \> 25 for age 65 to 75; CAARS-S:S \> 60) * The cut-score of 25 used for participants age 65 to 75 because lower cut-score has been recommended for older Veterans (Yeager and Magruder, 2014) * ADHD has been recognized as a neurobehavioral impairment in executive function (Brown, 2008) * Veterans with PTSD at this age range are suited for this study because statistically they have fewer confounding variables for this clinical trial, including medical conditions such as hypertension or glaucoma and cognitive impairments such as dementia * Physical health good enough to be able to participate in the study * Competent to give informed consent Exclusion Criteria: * Age younger than 18 or greater than 75 * Age becomes the main risk factor for major neurocognitive disorder, especially after 75 (Sousa et al, 2020) * Known sensitivity to ATX * Presence of disorders that could conceivably be exacerbated by atomoxetine * specifically, narrow angle closure glaucoma, urinary outflow obstruction, hypertension, and neurological disorders, particularly tics and Tourette's syndrome, or a history of epilepsy or seizures * Subjects with major traumatic brain injury (TBI) determined by Ohio State University Traumatic Brain Injury Identification Method (OSU-TBI ID) * However, mild TBI, assessed with OSU-TBI ID and review of record will be allowed to participate in this trial * Use of co…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)

Timeframe: 15 minutes

Trial details

NCT IDNCT06573970

SponsorVA Office of Research and Development

Sponsor typeFED

Study typeINTERVENTIONAL

Primary completion2029-06-29

Contact for this trial

Zhewu Wang, MD

(843) 789-7949 zhewu.wang@va.gov

View on ClinicalTrials.gov More Posttraumatic Stress Disorder With Attention Defic trials