Prolonged Exposure Therapy + Medication for PTSD

Recruiting in Palo Alto (17 mi)

+6 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Pennsylvania

Must not be taking: MAO inhibitors

Disqualifiers: Suicidal ideation, Active psychosis, Manic episodes, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Posttraumatic Stress Disorder (PTSD) remains a salient and debilitating problem, in the general population and for military veterans in particular. Several psychological and pharmacological treatments for PTSD have evidence to support their efficacy. However, the lack of comparative effectiveness data for PTSD treatments remains a major gap in the literature, which limits conclusions that can be drawn about which of these treatments work best. The current study will compare the effectiveness of PTSD treatments with the strongest evidentiary support - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine - as well as the combination of these two treatments. A randomized trial will be conducted with a large, diverse sample of veterans with PTSD (N = 300) recruited from 6 VA Medical Centers throughout the US. Participants will complete baseline assessments, followed by an active treatment phase (involving up to 14 sessions of PE and/or medication management) with mid (7 week) and posttreatment (14 week) assessments, and follow-up assessments at 27 and 40 weeks. Study outcomes will include PTSD severity, depression, quality of life and functioning, assessed via clinical ratings and self-report measures. Further, a range of demographic and clinically relevant variables (e.g., trauma type/number, resilience) will be collected at baseline and examined as potential predictors or moderators of treatment response, addressing another gap in the PTSD treatment literature. These data will be used to develop algorithms from predicting the optimal treatment for individual patients (i.e., "personalized advantage indices"; PAIs). Effectiveness of the treatments will be compared using multilevel modeling. PAIs will be developed by conducting bootstrapped analyses to select variables that predict or moderate outcomes (clinician rated PTSD severity at Week 14), followed by jacknife analyses to determine the magnitude of the predicted difference (representing an individual's "predicted advantage" of one treatment over the others).

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that ongoing treatments that could interact with the trial medications (paroxetine and venlafaxine) may exclude you from participating. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Prolonged Exposure Therapy + Medication for PTSD?

Research shows that Prolonged Exposure Therapy (PE) is highly effective for PTSD, with strong evidence supporting its use. Medications like paroxetine and venlafaxine XR have also shown promise in treating PTSD, and combining these with PE may enhance treatment outcomes, although more research is needed to compare their combined effectiveness.

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Is the combination of Prolonged Exposure Therapy and medications like Paroxetine and Venlafaxine XR safe for treating PTSD?

Paroxetine and Venlafaxine XR have been studied for PTSD and other anxiety disorders, showing they are generally safe and effective in both short-term and long-term use. These medications are well-tolerated in adults, although individual responses can vary.

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How does the treatment of Prolonged Exposure Therapy combined with Paroxetine or Venlafaxine XR differ from other PTSD treatments?

This treatment is unique because it combines Prolonged Exposure Therapy, which is a well-supported psychological approach, with medications like Paroxetine or Venlafaxine XR, which are antidepressants. This combination aims to enhance the effectiveness of therapy for those who do not fully respond to therapy alone, offering a potentially more comprehensive approach to managing PTSD symptoms.

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Eligibility Criteria

This trial is for military veterans who have been diagnosed with PTSD, can give informed consent, and speak English. They must be willing to undergo Prolonged Exposure therapy or take medications like paroxetine or venlafaxine XR, or both. Veterans who've had a failed trial of these therapies, active psychosis, certain medical conditions that conflict with the treatments, recent suicidal behavior, or history of manic episodes cannot participate.

Inclusion Criteria

I have been diagnosed with PTSD.

I am able to understand and agree to the study's procedures and risks.

fluent in English

Exclusion Criteria

I have had episodes of mania in the past.

I am not on any treatments that clash with paroxetine or venlafaxine.

I have tried Prolonged Exposure therapy or medications like paroxetine and venlafaxine XR without success.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete baseline assessments to collect demographic and clinically relevant variables

1 week

Active Treatment

Participants receive up to 14 sessions of Prolonged Exposure therapy and/or pharmacotherapy with paroxetine or venlafaxine

14 weeks

Up to 14 sessions (in-person or via telehealth)

Mid-treatment Assessment

Mid-treatment assessments conducted to evaluate progress

1 week

Post-treatment Assessment

Post-treatment assessments conducted to evaluate treatment outcomes

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Assessments at 27 and 40 weeks

Participant Groups

The study compares the effectiveness of Prolonged Exposure (PE) therapy and pharmacotherapy using paroxetine or venlafaxine XR against their combination in treating PTSD. Participants will receive up to 14 sessions of PE and/or medication management over several weeks with follow-up assessments to measure treatment impact on PTSD severity and quality of life.

Group I: Prolonged Exposure Therapy Active Control 1 Intervention

8-14 sessions of psychotherapy, each lasting 60-90 minutes, focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders

Group II: Pharmacotherapy Active Control 1 Intervention

20-60mg of paroxetine daily, or 75-300mg of venlafaxine XR daily

Group III: Combined treatment (Prolonged Exposure and Pharmacotherapy) Active Control 2 Interventions

8-14 sessions of psychotherapy, each lasting 60-90 minutes, focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders AND 20-60mg of paroxetine daily, or 75-300mg of venlafaxine XR daily

Paroxetine is already approved in United States, European Union, Australia, Canada for the following indications:

🇺🇸 Approved in United States as Paxil for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Panic disorder
• Social anxiety disorder
• Generalized anxiety disorder
• Posttraumatic stress disorder

🇪🇺 Approved in European Union as Seroxat for:

• Major depressive episodes
• Obsessive-compulsive disorder
• Panic disorder with or without agoraphobia
• Social anxiety disorder
• Generalized anxiety disorder
• Posttraumatic stress disorder

🇦🇺 Approved in Australia as Aropax for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Panic disorder
• Social anxiety disorder
• Generalized anxiety disorder
• Posttraumatic stress disorder

🇨🇦 Approved in Canada as Paxil for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Panic disorder
• Social anxiety disorder
• Generalized anxiety disorder
• Posttraumatic stress disorder

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Birmingham VA Healthcare System Birmingham, AL

Corporal Michael J. Crescenz VA Medical Center Philadelphia, PA

Milwaukee VA Medical Center Milwaukee, WI

VA North Texas Healthcare System Dallas, TX

More Trial Locations

Who Is Running the Clinical Trial?

University of Pennsylvania Lead Sponsor

Birmingham VA Health Care System Collaborator

San Diego Veterans Healthcare System Collaborator

VA Palo Alto Health Care System Collaborator

Patient-Centered Outcomes Research Institute Collaborator

Corporal Michael J. Crescenz VA Medical Center Collaborator

Coatesville VA Medical Center Collaborator

Milwaukee VA Medical Center Collaborator

North Texas Veterans Healthcare System Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Paroxetine CR augmentation for posttraumatic stress disorder refractory to prolonged exposure therapy. [2022] Little is known about the efficacy of "next step" strategies for patients with post-traumatic stress disorder (PTSD) who remain symptomatic despite treatment. This study prospectively examines the relative efficacy of augmentation of continued prolonged exposure therapy (PE) with paroxetine CR versus placebo for individuals remaining symptomatic despite a course of PE.

2. England pubmed.ncbi.nlm.nih.gov

Extended-release formulation of venlafaxine in the treatment of post-traumatic stress disorder. [2015] There is abundant evidence for abnormalities of both norepinephrine and serotonin neurotransmitter systems in post-traumatic stress disorder (PTSD). Venlafaxine extended-release formulation (venlafaxine XR) is a serotonin and norepinephrine re-uptake inhibitor with antidepressant and anxiolytic properties relevant to the pathophysiology of PTSD. Venlafaxine XR is currently approved for the treatment of panic disorder, generalized anxiety disorder and social anxiety disorder, as well as major depression in adults, based on a number of randomized, double blind, placebo-controlled clinical trials. Limited data also demonstrate that venlafaxine XR maintains a therapeutic response for more than 6 months in these anxiety disorders. Venlafaxine XR has demonstrated short- and long-term efficacy for the treatment of PTSD in two recent randomized, double-blind, placebo-controlled clinical trials, although it has not been extensively studied for PTSD, compared with other anxiety disorders. This review focuses on the potential role of venlafaxine XR in the treatment of PTSD, based on currently available evidence.

3. United States pubmed.ncbi.nlm.nih.gov

Patient and Clinical Factors Associated With Response to Medications for Posttraumatic Stress Disorder. [2022] Objective: Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD) in randomized clinical trials. Two prior studies using Department of Veterans Affairs (VA) medical records data show these medications are also effective in routine practice. Using an expanded retrospective cohort, we assessed the possibility of differential patterns of response based on patient and clinical factors.

4. United States pubmed.ncbi.nlm.nih.gov

A comparison of prolonged exposure therapy, pharmacotherapy, and their combination for PTSD: What works best and for whom; study protocol for a randomized trial. [2022] Several efficacious psychological and pharmacological treatments for posttraumatic stress disorder (PTSD) are available; however, the comparative effectiveness of these treatments represents a major gap in the literature. The proposed study will compare the effectiveness of two leading PTSD treatments - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine extended release - as well as the combination of PE and medication.

5. United States pubmed.ncbi.nlm.nih.gov

A Clinician's Guide to PTSD Treatments for Returning Veterans. [2021] What options are available to mental health providers helping clients with posttraumatic stress disorder (PTSD)? In this paper we review many of the current pharmacological and psychological interventions available to help prevent and treat PTSD with an emphasis on combat-related traumas and Veteran populations. There is strong evidence supporting the use of several therapies including prolonged exposure (PE), eye movement desensitization and reprocessing (EMDR), and cognitive processing therapies (CPT), with PE possessing the most empirical evidence in favor of its efficacy. There have been relatively fewer studies of non-exposure based modalities (e.g., psychodynamic, interpersonal, and dialectical behavior therapy perspectives), but there is no evidence that these treatments are less effective. Pharmacotherapy is promising (especially paroxetine, sertraline, and venlafaxine), but more research comparing the relative merits of medication vs. psychotherapy and the efficacy of combined treatments is needed. Given the recent influx of combat-related traumas due to ongoing conflicts in Iraq and Afghanistan, there is clearly an urgent need to conduct more randomized clinical trials research and effectiveness studies in military and Department of Veterans Affairs PTSD samples. Finally, we provide references to a number of PTSD treatment manuals and propose several recommendations to help guide clinicians' treatment selections.

6. England pubmed.ncbi.nlm.nih.gov

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies. [2022] Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to specific treatments. Paroxetine is a selective serotonin re-uptake inhibitor that has been found effective in the treatment of major depression as well as a range of anxiety disorders. This paper reviews data on the use of paroxetine for the treatment of adult PTSD. There have been three 12-week, placebo-controlled studies of paroxetine in PTSD. As these followed a partly similar design, a pooled analysis of the studies is possible and is reported here. Paroxetine is effective in the short-term treatment of PTSD, resulting in significantly better response and remission rates than placebo, improving sleep disturbance and reducing each of the symptom clusters of PTSD, as well as the disability associated with this condition. The medication is effective in both male and female PTSD patients and whether or not there are comorbid disorders such as depression.

7. United States pubmed.ncbi.nlm.nih.gov

Comparing Medications for DSM-5 PTSD in Routine VA Practice. [2022] Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD). One prior study using US Department of Veterans Affairs (VA) medical records data to compare these agents found no differences in symptom reduction in clinical practice. The current study addresses several weaknesses in that study, including limited standardization of treatment duration, inability to account for prior treatment receipt, use of an outdated symptomatic assessment for PTSD, and lack of functional outcome.

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. [2023] Background: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. Objectives: To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. Results: Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.28, 95% CI -0.39 to -0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. Conclusions: Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.

9. United States pubmed.ncbi.nlm.nih.gov

Prolonged exposure therapy for chronic combat-related PTSD: a case report of five veterans. [2019] Prolonged exposure (PE) therapy has been found efficient in reducing posttraumatic stress disorder (PTSD) symptoms mostly among rape victims, but has not been explored in combat-related PTSD. Five patients with severe chronic PTSD, unresponsive to previous treatment (medication and supportive therapy) are described. Patients were evaluated with the PTSD Symptom Scale-Interview, and Beck Depression Inventory, before and after 10-15 sessions of PE therapy. All five patients showed marked improvement with PE, with a mean decrease of 48% in PTSD Symptom Scale-Interview score and 69% in Beck Depression Inventory score. Moreover, four patients maintained treatment gains or kept improving 6-18 months after the treatment. The results suggest that PE was effective in reducing combat-related chronic PTSD symptoms.