Combined Treatment of Prolonged Exposure and Pramipexole for Posttraumatic Stress Disorder and Depression

Approximately half of the individuals with posttraumatic stress disorder (PTSD) present with
major depressive disorder (MDD). Compared to PTSD alone, patients with comorbid PTSD-MDD
demonstrate greater distress and poorer treatment outcome. Functional magnetic resonance
imaging (fMRI) show that relative to PTSD alone, PTSD-MDD is associated with decreased
resting state functional connectivity (rs-FC) in both fear- and reward-processing circuits.
In addition, our data suggest that Prolonged Exposure (PE), first-line PTSD treatment, may
successfully target impairments in the fear circuits, but not in the reward circuits, which
may explain the treatment-refractory quality of PTSD-MDD.

The goal of this pilot study is to test the feasibility, safety and initial efficacy of an
integrated therapeutic approach targeting both fear and reward impairments in PTSD-MDD
patients. Specifically, the investigators will examine a combination treatment with PE, shown
to effectively address fear circuitry deficits, and Pramipexole, a dopamine agonist, shown to
increase reward circuit function and to have promise in treating depression but not
previously studied in PTSD. The central hypothesis is that combined PE/Pramipexole will a)
improve PTSD and depressive symptoms in PTSD-MDD patients, and b) increase functional
connectivity of fear and reward pathways as measured by fMRI rs-FC. In this pilot study, 15
adults aged 18-60 years with PTSD-MDD will receive combined 10-week of PE and Pramipexole up
to the maximum dose of 4mg a day. Clinical assessment will be conducted at baseline, week 5,
post treatment and at 3-month follow up. Behaviorally assessments including the probabilistic
reward task (PRT) and attention allocation tasks, and fMRI scans for resting state functional
connectivity (rs-FC) will be conducted at baseline and end of treatment.

Inclusion Criteria:

1. Males or females between the ages of 18 and 60

2. Current DSM-V diagnosis of PTSD comorbid with MDD

3. CAPS-5 ≥ 25, and 17-item HRSD ≥ 17

4. Able to give consent, fluent in English

Exclusion Criteria:

1. Prior or current diagnosis with traumatic brain injury, bipolar disorder, psychotic
disorder, gambling or impulse control disorders, or dementia

2. History of psychosis, psychotic disorder, mania or bipolar disorder

3. Severe substance use disorder excluding nicotine (i.e., nicotine use disorder and
mild-moderate alcohol/cannabis use disorder are accepted)

4. Individuals at risk for suicide based on history and current mental state. BDI-II
suicide item > 2 or CGI-Severity baseline score of 7.

5. Treatment with antidepressants or other psychotropic medication in the past 4 weeks
(or 6 weeks for fluoxetine; an exception will be made for zolpidem used intermittently
for sleep).

6. Pregnancy or plans to become pregnant during the period of the study.

7. Current psychotherapy

8. Current unstable or untreated medical illness

9. Any condition that would exclude clinical MRI exam (e.g. pacemaker, paramagnetic
metallic prosthesis, surgical clips, shrapnel, necessity for constant medicinal patch,
some tattoos, severe obesity, claustrophobia)

10. History of untoward reaction to pramipexole