Combat Veterans with posttraumatic stress disorder (PTSD) often show cognitive impairments in attention, working memory, executive functions, and inhibitory control, a cluster of symptoms resembling symptoms of ADHD. The presence of comorbid ADHD cognitive symptoms is often associated with greater PTSD clinical severity and poorer treatment outcomes. While treatments for the avoidance, arousal, and re-experiencing symptoms associated with PTSD for military personnel are readily available, substantial gaps exist in the treatment of the cognitive deficits associated with PTSD. As a result, untreated co-occurring ADHD cognitive symptoms in PTSD may have severe negative impacts on patients' functional recovery, treatment outcome, and quality of life. Given that up to 50% of patients do not respond well to the first-line PTSD treatments, it is imperative to seek novel treatment strategies toward cognitive improvement that will improve both standard treatment response and daily functional recovery. The proposed study directly addresses this knowledge gap by testing the efficacy of atomoxetine (ATX) in reducing ADHD cognitive symptoms among veterans with comorbid ADHD/PTSD. ATX is a non-stimulant selective norepinephrine reuptake inhibitor (SNRI), approved by FDA for treatment of ADHD. Studies suggest that ATX, unlike stimulant, lacks addictive properties and shows efficacy in the treatment of comorbid depression and anxiety, which is ideal in treatment of comorbid ADHD and PTSD. The objective of this application is to examine the impact of ADHD cognitive symptoms on PTSD clinical outcomes, and to assess the efficacy of ATX in enhancing the cognitive function, improving quality of life, and treatment outcomes in veterans with comorbid PTSD/ADHD. Our recent research uncovered a higher prevalence of ADHD symptoms among combat veterans with PTSD (45%) than among those without PTSD (11%), and the comorbid ADHD symptoms was correlated with PTSD clinic severity. Treatment with methylphenidate showed improvement in their academic and occupational performance, and improvement in the PTSD treatment outcome in patients with comorbid ADHD/PTSD. Based on our findings, we hypothesize that 1) comorbid ADHD symptoms is a risk for treatment resistance, and 2) treatment with ATX will reduce ADHD cognitive symptoms, facilitate functional recovery, and improve veterans' quality of life and PTSD treatment outcomes. To accomplish our objective, we aim to: 1) examine the impact of ADHD symptoms on treatment response in Veterans with PTSD; 2) assess the efficacy and safety of add-on ATX as compared with placebo in relieving ADHD cognitive symptoms, improving cognitive function and veterans' quality of life; 3) evaluate the efficacy of add-on ATX as compared with placebo in reducing PTSD symptoms. To achieve these aims, we will conduct a pilot prospective, 10-week, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial of ATX as an add-on medication to other therapies in Veterans with comorbid ADHD/PTSD. Primary outcome measures will be ADHD cognitive symptom reduction and quality of life improvement; and the secondary outcome measures will be PTSD and depressive symptoms reduction. The proposed work is innovative; it applies novel therapeutic agent to treat cognitive symptoms in PTSD. To our knowledge, this is the first study to apply a SNRI to address an often overlooked PTSD-cognitive deficit. Our research is directly responsive to the mission of RR&D-SPiRE to maximize functional recovery of cognitive function in PTSD. The outcome of the proposed research will be significant, because it provides a knowledge base to help determine who is at risk for developing treatment resistance among PTSD patients, thereby allowing for development of early intervention strategies. More importantly, the new knowledge may lead to discovering new targets for novel and more effective treatments for PTSD. This clinical trial may immediate benefit Veterans by enhancing their cognitive function, reducing ADHD symptoms related disability, and further improving quality of life for veterans suffer from comorbid ADHD/PTSD.

Public Health Relevance

PTSD is associated with cognitive impairments in attention, executive function and inhibitory control, which often causes significant functional impairment and poses staggering personal, social burden. Given that up to 50% of patients do not respond to the standard PTSD treatments, it is imperative to seek novel treatment strategies toward cognitive function that will improve both standard treatment response and daily functional recovery. In response to RR&D RFA SPiRE, we will conduct a small clinical trial to test feasibility, safety, and efficacy of atomoxetine in improving cognitive function and treatment response in Veterans with PTSD. The proposed work is innovative; it applies novel approaches to assess the efficacy of ATX in improving treatment outcome in comorbid ADHD/PTSD. These findings will immediately benefit Veterans and military personnel by improve their cognitive function and further to their quality of daily life. In a long run, the proposed studies may lead to novel clinical interventions for impairment due to cognitive dysfunction in PTSD.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (I21)
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Special Emphasis Panel (RRDS)
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Ralph H Johnson VA Medical Center
United States
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