Atomoxetine in Veterans With Comorbid ADHD/PTSD

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.

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