Norah Feeny, PhD - US grants

DESCRIPTION (provided by application): Posttraumatic stress disorder (PTSD) is a chronic and debilitating condition, with lifetime prevalence rates ranging from 8%-14% of the US population (Davidson et at., 1991; Breslau et al., 1991, 1998; Kessler et al., 1995). Thus, the development of efficacious and cost-effective treatments for PTSD is imperative. Both prolonged exposure therapy (PE) and sertraline (MED) are of established efficacy for PTSD. Yet, we know very little about the comparable effectiveness of these forms of treatment, nor what factors influence treatment acceptance/refusal and completion/drop-out. In this five-year, two-site study, we will examine these issues. This collaborative R01 grant will be conducted at the University of Washington under the direction of Dr. Zoellner and at Case Western Reserve University under the direction of Dr. Feeny. We will conduct a hybrid efficacy-effectiveness trial in which female and male trauma victims will be randomly assigned to either choice or no choice treatment conditions. In the choice condition, participants will choose between prolonged exposure and sertraline. In the no choice condition, participants will be randomly assigned to either prolonged exposure or sertraline. Outcome, as measured by both psychopathology and broader functioning measures, will be assessed through 24-month follow-up. The results of the proposed research will inform clinicians about the relative short-term and long-term effectiveness of PE and MED, provide information about how these treatments influence broader measures of functional impairment, provide information regarding decision making factors in order to maximize treatment utilization, and provide important information about cost effectiveness of both PE and MED for chronic PTSD.

sertraline; posttraumatic stress disorder; human therapy evaluation; mental disorder chemotherapy; psychotherapy; pharmacokinetics; dosage; patient oriented research; human subject; female; women's health; questionnaires; clinical research;

DESCRIPTION (provided by application): Posttraumatic stress disorder (PTSD) is a chronic and debilitating condition, with lifetime prevalence rates ranging from 8%-14% of the US population (Davidson et at., 1991; Breslau et al., 1991, 1998; Kessler et al., 1995). Thus, the development of efficacious and cost-effective treatments for PTSD is imperative. Both prolonged exposure therapy (PE) and sertraline (MED) are of established efficacy for PTSD. Yet, we know very little about the comparable effectiveness of these forms of treatment, nor what factors influence treatment acceptance/refusal and completion/drop-out. In this five-year, two-site study, we will examine these issues. This collaborative R01 grant will be conducted at the University of Washington under the direction of Dr. Zoellner and at Case Western Reserve University under the direction of Dr. Feeny. We will conduct a hybrid efficacy-effectiveness trial in which female and male trauma victims will be randomly assigned to either choice or no choice treatment conditions. In the choice condition, participants will choose between prolonged exposure and sertraline. In the no choice condition, participants will be randomly assigned to either prolonged exposure or sertraline. Outcome, as measured by both psychopathology and broader functioning measures, will be assessed through 24-month follow-up. The results of the proposed research will inform clinicians about the relative short-term and long-term effectiveness of PE and MED, provide information about how these treatments influence broader measures of functional impairment, provide information regarding decision making factors in order to maximize treatment utilization, and provide important information about cost effectiveness of both PE and MED for chronic PTSD.

DESCRIPTION (provided by applicant): Although it is well established that both pharmacological and psychological therapies are relatively effective in treating chronic posttraumatic stress disorder (PTSD), the recent Institute of Medicine (IOM, 2007) report highlights vast gaps in our current knowledge noting a lack of knowledge regarding factors influencing treatment acceptance and completion, the combined effectiveness of these pharmacological and psychological treatment, and their efficacy in common subpopulations (e.g., those with diagnostic co-occurrence). To address these gaps, we propose the first large-scale trial to directly focus on individualizing PTSD care across several key parameters: choice of treatment, the effects of combined psychotherapy and pharmacological PTSD treatment, and the presence of co-occurring major depression. Building on our previous psychotherapy and pharmacotherapy trial on PTSD treatment, we will conduct a doubly randomized preference trial in which female and male trauma survivors with chronic PTSD will be randomly assigned to either choice or no choice treatment conditions. In the choice condition, patients will choose between prolonged exposure (PE) and prolonged exposure plus sertraline (PE + SER). In the no choice condition, patients will be randomly assigned to either prolonged exposure alone (PE) or prolonged exposure plus sertraline (PE + SER). In addition, we will specifically recruit and examine patients with co-occurring major depressive disorder (MDD). Outcome, as measured by both psychopathology and broader functioning measures, will be assessed at post-treatment and through 24-month follow-up. We will also examine biopsychosocial markers of response, psychotherapy change processes, and cost-effectiveness of these treatments. The Specific Aims are: 1) To compare the short-term and long-term effectiveness of PE to that of PE + SER; 2) To systematically compare patients who have chosen their treatment to those who have not in terms of treatment adherence, treatment completion, and effectiveness; and 3) To compare individuals with PTSD alone to those with PTSD and co-occurring major depression. In line with the NIMH's strategic plan, this application focuses on more personalized medicine, focusing on patients' choices and better understanding individual trajectories of outcome.

PROJECT SUMMARY Evidence-based psychotherapies for posttraumatic stress disorder (PTSD) and depression consistently produce strong, clinically meaningful effects for many individuals. However, these interventions also have significant dropout rates, a large minority of individuals continue to have debilitating symptoms, and even those who respond may be vulnerable to relapse upon future stressors. More efficient and mechanistically precise interventions are needed. Consistent with the cross-cutting theme of studying the role of the environment in the NIMH Strategic Plan, the etiologic role of exposure to destabilizing, stressful life events is common to both PTSD and depression. Not only do they share common distress-related triggers, symptoms, and maintaining processes, but they also commonly co-occur (upwards of 60%). Current PTSD and depression treatments typically focus on their respective disorders rather than on common processes that maintain psychopathology; and, importantly, they do not explicitly target positive adaptive processes associated with resilience. Decades of experimental studies, prospective studies, and psychotherapy trials have identified interconnected maladaptive and adaptive processes associated with persistent psychopathology after stressful, destabilizing events. These maladaptive processes include: 1) unproductive event processing; 2) avoidance; and 3) reward sensitivity and processing deficits. These processes prolong negative mood, interfere with adaptive coping and processing of emotional material, and increase sensitivity to future stressful life events. PATH (Positive Processes and Transition to Health) directly targets these maladaptive processes while also teaching parallel adaptive skills (constructive processing, approach, and positive emotion processing and reward seeking). Six, 90-min sessions target individuals who have experienced a destabilizing life event and have persistent stressor-related symptoms. PATH utilizes life event processing (revisiting, meaning making), focusing repeatedly on an identified destabilizing life event, positive life events, and future events as a framework to identify maladaptive processes and teach constructive processing skills. In a small open trial (R61, N = 45), we will examine whether PATH engages the key targets of unproductive processing, avoidance, and reward deficits. Next, we will conduct a randomized trial of PATH (R33, N = 135), comparing PATH to a Progressive Muscle Relaxation, seeking to replicate changes in the targets in a larger sample and examine PATH's impact on stressor-related psychopathology (PTSD, depression). PATH, a brief and focused treatment that targets key psychological processes common to PTSD and MDD, has the potential to reduce dropout, improve treatment engagement and outcomes, identify potential treatment mechanisms, and ultimately reduce the costly human and economic burden of stressor-related psychopathology.