Atomoxetine and Executive Function in PTSD

Conditions

• Posttraumatic Stress Disorder With Attention Defic

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Accepted

Interventions

• Atomoxetine — DRUG
  Atomoxetine is a selective norepinephrine reuptake inhibitor medication used to treat attention deficit hyperactivity disorder (ADHD), and executive dysfunction. Dispensing of blinded medication (40mg to 80mg ATX or placebo) will begin at randomization and will be dispensed at weeks 2, 4, 8, and 12. The initial dose of ATX is 40mg or placebo and will be given for one week, the dose will be titrated to 80mg if tolerated in the second week through week 12.
• Placebo — DRUG
  placebo pill appears like real atomoxetine pill but has no therapeutic ingredient and benefit. The same schedule to distribution as Atomoxetine arm.

Study Details

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.

Key Dates

Start date

Apr 1, 2026

Status verified

Feb 2026

Primary completion

Jun 29, 2029

Completion

Sep 28, 2029

Study Design

Enrollment

160 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: active atomoxetine
  Active ATX (40mg capsules) will be prepared. Initial dose is 40mg, titrated to 80mg if tolerable in one week.
• Placebo Comparator: Placebo
  placebo pill appears like real atomoxetine pill but has no therapeutic ingredient and benefit. The same schedule to distribution as Atomoxetine arm.

Primary Outcome Measure

Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) [ Time Frame: 15 minutes ]

Central Contacts

• Zhewu Wang, MD
  (843) 789-7949
  [email protected]
• Mark B Hamner, MD BS
  (843) 789-7799
  [email protected]

Locations (1)

Find similar trials in Charleston, SC