Prolonged Exposure Therapy for PTSD and Opioid Use Disorder

Treating Posttraumatic Stress Disorder in Patients With Opioid Use Disorder

Among patients with opioid use disorder (OUD), 90% report lifetime trauma exposure and 33% meet criteria for posttraumatic stress disorder (PTSD). The co-occurrence of OUD and PTSD is associated with worse mental health and opioid agonist treatment (OAT) outcomes relative to either diagnosis alone. Prolonged exposure therapy (PET) is an efficacious cognitive-behavioral treatment for reducing PTSD severity. Although preliminary findings indicate that PET may reduce PTSD symptom severity among patients receiving treatment for concomitant OUD, it is unclear to what extent improvements were a function of PET versus the effects of OAT itself. Therefore, the question of whether OAT alone may attenuate PTSD symptoms in the absence of intensive cognitive-behavioral therapy remains unanswered.

In this 12-week trial, we aim to investigate the contribution of PET above and beyond OAT alone for reducing PTSD symptoms among adults with concurrent PTSD and OUD. Participants will be randomized to one of three conditions: (a) OAT as usual, (b) OAT + PET, or (c) OAT + Enhanced PET (OAT+PET+). Those randomized to OAT as usual will continue to receive standard buprenorphine or methadone treatment from their current treatment provider and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at intake and Study Weeks 4, 8, and 12. In addition to receiving OAT and completing monthly assessments, OAT+PET participants will receive PET consisting of 12 weekly, individual sessions with a trained therapist. Finally, OAT+PET+ participants will receive the procedures noted above for the OAT+PET group plus monetary incentives delivered contingent upon completion of PET sessions. Given the poor PET adherence rates reported among patients with substance use disorders, the use of incentives will ensure that we evaluate PET effects among patients who receive a sufficient dose of therapy. The proposed study design will permit us to disentangle the effects of PET from the effects of OAT alone while also including experimental conditions that reflect real-world practice. Taken together, this project will produce important new scientific and clinically-relevant information related to the mechanisms through which OAT and PET promote reductions in PTSD symptomatology in a highly vulnerable clinical population.

Study Overview

• Status: Completed
• Conditions: Post Traumatic Stress Disorder; Opioid-use Disorder
• Intervention / Treatment: Behavioral: Prolonged Exposure Therapy; Behavioral: Attendance-based monetary incentives

Detailed Description

Among patients with opioid use disorder (OUD), 90% report lifetime trauma exposure and 33% meet criteria for posttraumatic stress disorder (PTSD). The co-occurrence of OUD and PTSD is associated with more severe mental health symptoms and worse opioid agonist treatment (OAT) outcomes relative to either diagnosis alone. Prolonged exposure therapy (PET) is an efficacious manualized cognitive-behavioral treatment for reducing PTSD severity. Although preliminary findings indicate that PET may reduce PTSD symptom severity among patients receiving treatment for concomitant OUD, it is unclear to what extent observed improvements were a function of PET versus the psychopharmacological effects of OAT itself. Therefore, the question of whether OAT alone may attenuate PTSD symptomatology in the absence of intensive cognitive-behavioral therapy remains unanswered and is important given the prevalence and deleterious effects of PTSD among OAT patients, as well as the ever-present constraints on mental health resources in substance use treatment settings.

The present study will investigate the contribution of PET above and beyond OAT alone for reducing PTSD symptomatology among adults with concurrent PTSD and OUD. Eligible participants who complete the informed consent process will be randomized to one of three conditions: (a) OAT as usual, (b) OAT + PET, or (c) OAT + Enhanced PET (OAT+PET+). Those randomized to OAT as usual will continue to receive standard buprenorphine or methadone treatment from their current treatment provider and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at intake and Study Weeks 4, 8, and 12. Follow-up assessment visits will be conducted in-person at our clinic following all relevant COVID-19-related CDC guidelines and university safety protocols. However, study measures may also be administered remotely via phone or telemedicine to reduce the risk of COVID-19 transmission. In addition to receiving OAT and completing monthly assessments, OAT+PET participants will receive PET consisting of 12 weekly, individual sessions with a trained therapist. Therapy sessions will be conducted at our research clinic or remotely via telemedicine to reduce the risk of COVID-19 transmission. Finally, OAT+PET+ participants will receive the procedures noted above for the OAT+PET group plus monetary incentives delivered contingent upon completion of PET sessions. Given the poor PET adherence rates reported among patients with substance use disorder (SUDs), the use of incentives will ensure that we evaluate PET effects among patients who receive a sufficient dose of therapy.

For inclusion in the study, participants must meet the following criteria: (a) > 18 years of age, (b) currently maintained on a stable methadone or buprenorphine dose for the treatment of OUD for >1 month prior to the study, (c) endorse >1 lifetime traumatic event, and (c) meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) PTSD diagnostic criteria (American Psychiatric Association, 2013). Exclusion criteria include: (a) the presence of an acute psychotic disorder, bipolar disorder with an active manic episode (but not simply the presence of bipolar disorder), (b) imminent risk for suicide, (c) a medical condition that may interfere with consent or participation (e.g., organic brain syndrome, dementia, head injury, neuropathy, etc.), and (d) illiteracy in English.

Participants randomized to OAT as usual will continue to receive standard buprenorphine or methadone maintenance from their current treatment provider and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at Study Weeks 4, 8, and 12. Follow-up assessment visits will be conducted in-person at our clinic following all relevant COVID-19-related CDC guidelines and university safety protocols. However, study measures may also be administered remotely via phone or telemedicine to reduce the risk of COVID-19 transmission. In addition to receiving standard buprenorphine- or methadone-maintenance treatment as described above and completing monthly assessments, OAT+PET participants will also receive 12 individual sessions of PET. Therapy sessions will be conducted at our research clinic or remotely via telemedicine to reduce the risk of COVID-19 transmission. Beginning in Study Week 1, OAT+PET participants will complete weekly 60-minute PET sessions provided by a therapist trained in PET. Participants randomized to the OAT+PET+ condition will receive the procedures noted above for the OAT+PET group plus monetary incentives delivered contingent upon completion of PET sessions. Each consecutive attended session will increase the voucher amount so that each consecutively attended appointment is worth an incrementally higher dollar amount. To support completion of the full 12-week PET protocol, we will also incorporate additional strategically-placed bonuses into the reinforcement schedule with the goal of maximizing the percentage of subjects who complete the full 12-session protocol. First, to support consistent (vs. sporadic) attendance, participants will receive a bonus for every two consecutive sessions attended. Second, to support completion of the full PET protocol, participants will receive an additional bonus upon completion of Session 12.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vemont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• >18 years old
• currently maintained on a stable methadone or buprenorphine dose for >1 month prior to the study
• endorse >1 lifetime traumatic event
• meet current DSM-V posttraumatic stress disorder criteria

Exclusion Criteria:

• Presence of an acute psychotic disorder, bipolar disorder with an active manic episode
• imminent risk for suicide
• a medical condition that may interfere with consent or participation
• illiteracy in English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: OAT as usual; Those randomized to OAT as usual will continue to receive standard buprenorphine or methadone treatment and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at intake and Study Weeks 4, 8, and 12.
Active Comparator: OAT+PET; In addition to receiving OAT and completing monthly assessments, OAT+PET participants will receive 12 weekly PET sessions with a trained therapist.	Behavioral: Prolonged Exposure Therapy; Within the general population, prolonged exposure therapy (PET) is a widely-used, empirically-supported and manualized therapy that is regarded as a first-line cognitive-behavioral treatment for posttraumatic stress disorder (PTSD). PET is designed to disrupt the cycle of anxiety and avoidance that characterizes PTSD via sustained imaginal and in-vivo exposure exercises that deliberately and systematically expose patients to painful memories and current, real-life trauma reminders that were previously avoided, yet not inherently harmful. Overall, PET has well-documented efficacy for reducing PTSD symptom severity in both civilian and veteran populations. PET is effective for reducing PTSD symptoms regardless of whether it is delivered remotely or face-to-face. Recent data also suggest that PET can improve PTSD symptoms without exacerbating substance use or craving among patients with substance use disorders when PET and substance use disorder treatment are delivered concurrently.
Experimental: OAT+PET+; OAT+PET+ participants will receive the procedures for the OAT+PET group plus monetary incentives contingent upon completion of PET sessions	Behavioral: Prolonged Exposure Therapy; Within the general population, prolonged exposure therapy (PET) is a widely-used, empirically-supported and manualized therapy that is regarded as a first-line cognitive-behavioral treatment for posttraumatic stress disorder (PTSD). PET is designed to disrupt the cycle of anxiety and avoidance that characterizes PTSD via sustained imaginal and in-vivo exposure exercises that deliberately and systematically expose patients to painful memories and current, real-life trauma reminders that were previously avoided, yet not inherently harmful. Overall, PET has well-documented efficacy for reducing PTSD symptom severity in both civilian and veteran populations. PET is effective for reducing PTSD symptoms regardless of whether it is delivered remotely or face-to-face. Recent data also suggest that PET can improve PTSD symptoms without exacerbating substance use or craving among patients with substance use disorders when PET and substance use disorder treatment are delivered concurrently.; Behavioral: Attendance-based monetary incentives; Participants will earn vouchers that have monetary value for attending scheduled PET appointments. Each consecutive attended session will increase the voucher amount so that each consecutively attended appointment is worth an incrementally higher dollar amount. To support completion of the full 12-week PET protocol, we will also incorporate additional strategically-placed bonuses into the reinforcement schedule with the goal of maximizing the percentage of subjects who complete the full 12-session protocol. First, to support consistent (vs. sporadic) attendance, participants will receive a bonus for every two consecutive sessions attended. Second, to support completion of the full PET protocol, participants will receive an additional bonus upon completion of Session 12.; Other Names: Contingency management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Posttraumatic Stress Disorder (PTSD) Symptom Severity	Change in PTSD symptom severity will be measured by the total symptom severity score of the Clinician Administered PTSD Scale for DSM-V (CAPS-5). The CAPS-5 is a clinician-administered clinical interview that produces a total symptom severity score that is obtained by summing the scores for each of the 20 items. Scores range from 0-80 with lower scores indicating less severe symptoms of PTSD. A negative sign in front of a number represents a decrease in score and less severe PTSD symptoms at 12 weeks compared to baseline. A greater decrease in score represents greater reduction in symptoms (more positive outcomes).	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Posttraumatic Stress Disorder (PTSD) Symptom Severity	Mean PTSD symptom severity will be measured by the PTSD Checklist for DSM-V (PCL-5) total score. The PCL-5 is a self-report measure that produces a total score that is obtained by summing the scores for each of the the 20 items. Scores range from 0-80 with higher scores indicating more severe symptoms of PTSD.	12 weeks
Anxiety Symptom Severity	Mean anxiety symptom severity will be measured by the Beck Anxiety Inventory (BAI) total score. The BAI is a self-report measure that produces a total score that is obtained by summing the scores for each of the 21 items. Scores range from 0-63 with higher scores indicating more severe symptoms of anxiety.	12 weeks
Depression Symptom Severity	Mean depression symptom severity will be measured by the Beck Depression Inventory (BDI-II) total score. The BDI-II is a self-report measure that produces a total score that is obtained by summing the scores for each of the 21 items. Scores range from 0-63 with higher scores indicating more severe symptoms of depression.	12 weeks
Number of Participants Achieving Illicit Opioid Abstinence	Illicit opioid abstinence will be measured by the overall percentage of urinalyses biochemically verified to be abstinent for illicit opioids at the end of the intervention period.	12 weeks
Psychiatric Problems Related to Substance Use	Psychiatric problems related to substance use will be measured by the Addiction Severity Index (ASI) Psychiatric subscale score. The ASI is a clinician-administered structured interview. Scores for this subscale range from 0-1 with higher scores indicating more severe psychiatric consequences of substance use.	12 weeks
Number of Participants Who Report Abstinence From Illicit Non-opioid Substance Use	Abstinence from illicit non-opioid substance use will be measured by the Timeline Follow-back (TLFB). The TLFB will be administered by an interviewer and involves participants retrospectively estimating their illicit non-opioid substance use (e.g., amphetamines, benzodiazepines, cocaine) during the 30 days prior to the interview date. Abstinence from illicit non-opioid substance use will be measured by the overall number of participants reporting abstinence from illicit non-opioid substances .	12 weeks
Pain Intensity and Interference	For participants who endorsed the presence of pain during the past month, pain intensity and interference will be measured by Brief Pain Inventory -Short Form (BPI-SF). The BPI-SF is a self-report measure of pain intensity and interference in function during the past week. The pain intensity section of the BPI includes a rating of average pain intensity; whereas, the functional interference section consists of a rating of pain interference on general activity. Items assessing pain intensity and functional interference are scored from 0-10 with higher scores indicating greater pain severity and functional interference, respectively.	12 weeks
Delay Discounting	Rates of delay discounting will be measured by the Monetary Choice Questionnaire (MCQ). The MCQ is a 27-item self-report measure consisting of items that presents a choice between smaller, immediate and larger, delayed monetary rewards. Immediate reward values ranged from $11 to $80, delayed rewards ranged from $25 to $85 and the length of the delay ranged from 7 days to 186 days. "Discounting rates," or k-values, are calculated from individuals' choices across items and represent rates at which the individual devalues rewards overall. The estimate of participant's discounting "k" was estimated with the following formula: V = A/(1+kD) where V is the present discounted value of the reinforcer, A is the objective value of the reinforcer, D is the delay until the receipt of the reinforcer, and k is the derived parameter that corresponds to the rate of discounting. In this equation, larger k values correspond to greater discounting of delayed rewards, or preference for small	12 weeks
Insomnia Severity	Insomnia severity will be measured by the Insomnia Severity Index (ISI). The ISI is a self-report measure that consists of 7 items that are scored from 0-4. The ISI produces a total score that is obtained by summing the scores for each of the the 7 items. Scores range from 0-28 with higher scores indicating more severe symptoms of insomnia.	12 weeks

Collaborators and Investigators

• Sponsor: University of Vermont
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Kelly Peck, Ph.D., University of Vermont

Publications and helpful links

General Publications

• Peck KR, Badger GJ, Cole R, Higgins ST, Moxley-Kelly N, Sigmon SC. Prolonged exposure therapy for PTSD in individuals with opioid use disorder: A randomized pilot study. Addict Behav. 2023 Aug;143:107688. doi: 10.1016/j.addbeh.2023.107688. Epub 2023 Mar 11.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2021
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Substance Use; Post Traumatic Stress Disorder; Prolonged Exposure Therapy; Financial Incentives; Opioid-use Disorder; Opioid Agonist Therapy
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Narcotic-Related Disorders; Mental Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Substance-Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: CHRBSS #STUDY00000318; P20GM103644 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No