Benzodiazepine Taper With Cognitive Behavioral Therapy in Patients Using Prescription Opioids

Study Overview
=================
Brief Summary
-----------------
Taking prescription opioids for pain together with benzodiazepines for the treatment of anxiety disorders is not recommended by the U.S. Food and Drug Administration (FDA) because of the elevated risk of serious complications, including fatal overdose. However, this concurrent prescription use continues to be prevalent, likely due to the high comorbidity between pain and anxiety disorders. Efforts are urgently needed to reduce benzodiazepine use among patients taking opioids. Cognitive behavioral therapy (CBT) is a first-line treatment for anxiety disorders, and represents a safer and more effective treatment for anxiety disorders compared to benzodiazepines. The proposed study aims to make minor adaptations to a CBT protocol to facilitate benzodiazepine tapering and to then conduct a 2-arm randomized clinical trial with primary care patients who receive benzodiazepine and opioid prescriptions. Participants will be randomized to receive a telehealth-delivered intervention consisting of a gentle, 12-week benzodiazepine taper (BZT) with either CBT or a health education control (HE). Participants will be assessed at baseline, several points throughout treatment, at post-treatment, and at a 2-month follow-up assessment on benzodiazepine use, opioid use, and anxiety symptoms. Should CBT + BZT outperform HE + BZT, this intervention could make a significant impact by reducing major consequences of concurrent use of opioids and benzodiazepines, including mortality.

Official Title
-----------------
Augmenting the Efficacy of Benzodiazepine Taper With Telehealth-Delivered Cognitive Behavioral Therapy for Anxiety Disorders in Patients Using Prescription Opioids

Conditions
-----------------
Anxiety Disorders

Intervention / Treatment
-----------------
* Combination Product: Cognitive behavioral therapy for anxiety plus benzodiazepine taper
* Combination Product: Health education control plus benzodiazepine taper


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: taking prescribed BZs for at least 3 months prior to baseline and have a positive UDS for BZs at baseline currently experiencing significant distress or impairment due to their anxiety symptoms (i.e., score ≥ 6 on the OASIS during screening have been prescribed opioids for at least 3 months for pain management and have a positive UDS for prescribed opioids at baseline are between 18-85 years old are fluent in English have access to a digital device with internet access for telehealth are willing to reduce BZ use. Exclusion Criteria: pregnancy psychiatric symptoms requiring a higher level of care (i.e., severe suicidality, manic or psychotic symptoms not stabilized on medication) presence of any SUD other than tobacco use disorder, OUD (co-occurring with pain condition) or sedative/hypnotic use disorder) medical conditions that require ongoing treatment with benzodiazepines (e.g., certain seizure disorders) use of drugs other than BZs and opioids in the past 30 days (as indicated by UDS and self-report), with the exception of intermittent cannabis use (not meeting criteria for CUD) and use of alcohol above at-risk drinking cutoffs per US Dietary Guidelines marked cognitive impairment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive behavioral therapy for anxiety plus benzodiazepine taper<br>11 sessions of individual therapy consisting of exposure-based cognitive behavioral therapy that is designed specifically for assisting with benzodiazepine taper. This will be added to a gentle, 12-week benzodiazepine taper. CBT will be initiated for two sessions prior to the benzodiazepine taper initiation. | Combination Product: Cognitive behavioral therapy for anxiety plus benzodiazepine taper<br>* 11 sessions of individual therapy consisting of exposure-based cognitive behavioral therapy that is designed specifically for assisting with benzodiazepine taper. This will be added to a gentle, 12-week benzodiazepine taper. CBT will be initiated for two sessions prior to the benzodiazepine taper initiation.<br>|
| Active Comparator: Health education control plus benzodiazepine taper<br>11 sessions of individual therapy control consisting of psychoeducational topics related to health and well-being, along with the gentle, 12-week benzodiazepine taper. | Combination Product: Health education control plus benzodiazepine taper<br>* 11 sessions of individual therapy control consisting of psychoeducational topics related to health and well-being, along with the gentle, 12-week benzodiazepine taper.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence | number of sessions attended | at week 15 | 
| Treatment Satisfaction Questionnaire | This measure will be used to assess patient satisfaction and acceptability with the interventions. | at week 15 | 
| Timeline Followback (change in benzodiazepine and opioid use and dose) | Timeline Followback (TLFB) will be used to assess BZ use and dose, opioid use and dose, and other substance use (and frequency and quantity). BZ dose at each assessment period will be assessed via self-report. Data will be gathered with the Timeline Followback (TLFB62), and facilitated by a dose diary card that patients will be given to track substance use (i.e., days of use of each drug including BZs) and dose of BZ on each day of BZ use. The diary card will only be used as a tool for participant recall during the TLFB administration, and will not be collected as data. TLFB administration will also be enhanced by asking patients to show their BZ pill bottles TLFB will be used to document self-reported use of substances for each day since the last TLFB assessment during the acute treatment phase (i.e., past 7 days during weekly study visits) and in the past 30 days for baseline, post-treatment, and follow-up (past month) | Baseline, weeks 1-14, post-treatment (week 15), and 2 months from week 15 | 
| Depression Anxiety and Stress Scale (change in scores over time) | Primary outcome measure to assess anxiety symptoms (anxiety subscale will be primary; depression and stress subscales will be examined as secondary) | Baseline, weeks 1-14, post-treatment (week 15), and 2 months from week 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Drug Screen (UDS) | UDS panel will include benzodiazepines, opiates, buprenorphine, and oxycodone at baseline and follow-up; UDS will also test for other substances including cocaine, amphetamines, and THC. | Baseline, post-treatment (week 15), and 2 months from week 15 | 
| California prescription drug monitoring database (CURES) | Opioid and benzodiazepine prescriptions (including dose) will be corroborated by review of the CURES system. | Baseline, weeks 1-14, post-treatment (week 15), and 2 months from week 15 | 
| Anxiety Sensitivity Index-3 (change) | The ASI-3 measures anxiety sensitivity (cognitive misappraisals of anxiety as being harmful, or fear of fear.). ASI-3 will be given frequently throughout treatment to establish temporal precedence needed to assess for possible mediation of treatment outcomes. | Baseline, bi-weekly during weeks 1-14, post-treatment (week 15), and 2 months from week 15 | 
| Pain Catastrophizing Scale (change) | The Pain Catastrophizing Scale will be used as a secondary outcome associated with opioid prescription use and will be given frequently throughout treatment to establish temporal precedence needed to assess for possible mediation of treatment outcomes. | Baseline, bi-weekly during weeks 1-14, post-treatment (week 15), and 2 months from week 15 |