Clinical trial NCT02287038: Atomoxetine in Veterans With Comorbid ADHD/PTSD
Official title: Atomoxetine in Comorbid ADHD/PTSD: A Pilot, Placebo-Controlled Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Post Traumatic Stress Disorder
Attention Deficit Hyperactivity Disorder
Keywords: PTSD
ADHD
Atomoxetine
Combat Trauma
Cognitive Deficit
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2014-11-10
Enrollment: 44
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A small prospective, 10-week, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial of atomoxetine as an add-on medication to other therapies in Veterans with comorbid ADHD/PTSD.
Primary purpose: TREATMENT

Brief summary: The current available treatments for PTSD are not fully effective for cognitive symptoms of PTSD and have high drop-out and poor engagement, two factors found to be most indicative of overall return to functioning for patients with PTSD. The proposed study directly addresses this knowledge gap by conducting a pilot, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial using atomoxetine (ATX) as an add-on medication to other therapies to testing the efficacy of ATX in reducing ADHD cognitive symptoms among veterans with comorbid ADHD/PTSD. Successful completion of this pilot clinical trial may build a platform for future large scale double-blind, placebo-controlled studies using either atomoxetine or other cognitive enhancing medications.

Detailed description: 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. The proposed study directly addresses this knowledge gap by testing the feasibility and preliminary efficacy of atomoxetine (ATX) in treatment of ADHD cognitive symptoms among those with comorbid ADHD/PTSD. This is a small 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 as measured by the Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S) and the Adult ADHD Quality of Life-29 (AAQoL-29). Secondary outcome measures will be PTSD and depressive symptoms reduction as measured by the Clinician Administered PTSD Scale (CAPS), the Hamilton Depression Scale (HAM-D). In addition to subjective measures, the response inhibition task Go/NoGo (GNG) will be used as objective assessments to measure ATX treatment outcomes. 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. This study 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, 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.

Eligibility criteria: Inclusion Criteria:

* Veterans age 20 to 60 with PTSD and significant ADHD symptoms (CAARS-S:S \> 65);
* Good physical health.
* Evidence of combat as defined by:

  * Trauma exposure sufficient to meet Category A of PTSD criteria (Breslau and Kessler 2001)

Exclusion Criteria:

* Age younger than 20 or greater than 60.
* Known sensitivity to ATX
* Presence of disorders that could conceivable 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).
* Use of concomitant medication that could potentially interact with atomoxetine including monoamine oxidase inhibitors (MAOI), antihypertensive medication, or any concomitant medication that was a cytochrome 2D6 inhibitor (CYP2D6), since atomoxetine's elimination involves the CYP2D6 system.
* An active or lifetime major mental health diagnosis as determined by DSM-IV Axis I 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 presence of depressive disorders if the depressive episodes are secondary to PTSD.
* Current substance dependence and abuse (within 3 month).
* Females who are pregnant.
* Suicidal thoughts and behavior. b. Sources of Material

Primary outcomes:
measure: Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999)
timeFrame: Visit 1, (Day1), Visit 4(Day 36), Visit 7 (Day 71)
measure: The Adult ADHD Quality of Life-29 (AAQOL-29, Brod et al, 2006)
timeFrame: Visit 1 (Day1), 4(Day 36), 7 (Day 71)
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center, Charleston, SC
state: South Carolina
Study officials:
affiliation: Ralph H. Johnson VA Medical Center, Charleston, SC
name: Zhewu Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang Z, Zuschlag ZD, Myers US, Hamner M. Atomoxetine in comorbid ADHD/PTSD: A randomized, placebo controlled, pilot, and feasibility study. Depress Anxiety. 2022 Apr;39(4):286-295. doi: 10.1002/da.23248. Epub 2022 Mar 21.