Opioid/Benzodiazepine Polydrug Abuse

Official title

Opioid/Benzodiazepine Polydrug Abuse: Integrating Research on Mechanisms, Treatment and Policies

Overview

Benzodiazepine (BZD)/opioid polysubstance abuse (PSA) dramatically increases risks of overdose, disability and death; however, little is known about phenotypes that could be targeted to decrease this use and these associated risks. The opioid abuse epidemic is generating unprecedented numbers of overdoses (OD) and deaths from prescribed and illegal sources (e.g. fentanyl combined with, or sold as, heroin). Yet, medical and epidemiological data suggest these adverse outcomes are not solely due to over-consumption of opioids.The FDA recognizes the health danger of BZD/opioid PSA, and issued labeling changes for prescribing BZDs and opioids. Impact of these changes is unclear and could be minimal if people obtain these substances illegally. BZD abuse can be harmful alone or combined with opioids, as BZDs: (a) contribute to OD/death e.g. 31% of opioid OD-related deaths from 1999 to 2011 were related to coincident BZD use, BZD co-use is dose-dependently related to mortality and rates of BZD OD deaths have sharply increased. (b) exacerbate progression and adverse outcomes of opioid abuse. and (c) worsen behavioral impairment from opioids, increase rates of falls and fractures, motor vehicle accidents, and sleep-disordered breathing. There has been limited systematic research of BZD/opioid PSA. This is a major gap because BZD are often co-prescribed with opioids (in 33 to 50% of cases) and are easily obtained illegally. In response to these problems, there is an urgent need to obtain population-level, clinical pharmacology, and mechanistic data to test our unified hypothesis of dual-deficit in affective/hedonic regulation.

Detailed description

Up to 120 patients who are currently in Substance Use Disorder treatment in Wayne County who use opioids, benzodiazepines (BZD), or both, will be assessed. Patients will be referred from the treatment regulator and local providers, and by advertisements in the community.

Participants will take part in one 6 hour face-to-face assessment during which they will undergo comprehensive assessments of both clinical (substance use, mental health) and hypothesis-driven measures (affective, neurocognitive, behavioral).

Participants must provide a supervised alcohol-free breath sample and a urine sample that will be screened for opioids, methadone, cocaine metabolites, BZDs, barbiturates, amphetamines.

Psychopathology: The Semi-Structured Clinical Interview for DSM-5 will be used to evaluate lifetime and current psychiatric and substance use disorders.

Affective dysregulation (inability to regulate emotions), neurocognition, pain and prescription misuse, insomnia, sleepiness, vigilance, and substance use will be assessed through the use of computerized measurements as well as paper and pencil questionnaires and face-to-face interviews.

Sample Size: Up to 120 total participant will be evaluated. This will offer greater statistical power to detect affective and neurocognitive effects than prior studies, including analysis of sex differences and correction for multiple comparisons.

Interventions

• Other Multi-domain assessment battery
  Assessments of emotion regulation, neurocognitive performance, pain, sleep, and substance use. There is no therapeutic intervention; all participants are already independently in treatment for their substance use disorder and we are simply assessing them at baseline visit and 3-month follow-up.

Primary outcome measures

• Psychopathology [Time frame: Administered once during the baseline clinical assessment.]
• Beck Depression Inventory-II [Time frame: Administered during the baseline clinical assessment, and at the 3-month follow-up visit.]
• Snaith-Hamilton Pleasure Scale [Time frame: Administered during the baseline clinical assessment, and at the 3-month follow-up visit.]
• Perceived Stress Scale [Time frame: Administered during the baseline clinical assessment, and at the 3-month follow-up visit.]
• State-Trait Anxiety Inventory [Time frame: Administered during the baseline clinical assessment, and at the 3-month follow-up visit.]
• Difficulties with Emotion Regulation Scale [Time frame: Administered during the baseline clinical assessment, and at the 3-month follow-up visit.]
• Alcohol and Drug Use Self-Efficacy Scale [Time frame: Administered during the baseline clinical assessment, and at the 3-month follow-up visit.]
• Distress Tolerance Scale [Time frame: Administered once during the clinical assessment.]
• Positive and Negative Affect Schedule-Short Form: Positive Affect [Time frame: Administered once during the baseline clinical assessment.]
• Positive and Negative Affect Schedule-Short Form: Negative Affect [Time frame: Administered once during the baseline clinical assessment.]

Eligibility criteria

Inclusion criteria

• Recently admitted and/or not clinically stable in treatment for Substance Use Disorder (SUD) in Wayne County
• Using opioids, benzodiazepines (BZD), or BZD/opioid.

Exclusion criteria

• Participants with current psychosis, bipolar disorder, or severe depression (i.e. severe psychiatric disorder)
• Individuals with serious neurological disorders, e.g. brain tumor, history of stroke, history of traumatic brain injury w/ loss of consciousness
• Cognitive impairment (IQ<80)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

United States · 1 center

• Tolan Park Medical Building — Detroit

Publications

• Greenwald MK, Moses TEH, Lundahl LH, Roehrs TA. Anhedonia modulates benzodiazepine and opioid demand among persons in treatment for opioid use disorder. Front Psychiatry. 2023 Jan 19;14:1103739. doi: 10.3389/fpsyt.2023.1103739. eCollection 2023. PMID 36741122

Identifiers

NCT: NCT03696017 · Polydrug Aim 2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗