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Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges.

ABSTRACT: Opioid abuse and related overdose deaths continue to rise in the United States, contributing to the current national opioid crisis. Although several opioid-based pharmacotherapies are available (e.g., methadone, buprenorphine, naloxone), they show limited effectiveness in long-term relapse prevention. In response to the opioid crisis, the National Institute on Drug Abuse proposed a list of pharmacological targets of highest priority for medication development for the treatment of opioid use disorders (OUD). Among these are antagonists of dopamine D3 receptors (D3R). In this review, we first review recent progress in research of the dopamine hypothesis of opioid reward and abuse and then describe the rationale and recent development of D3R ligands for the treatment of OUD. Herein, an emphasis is placed on the effectiveness of newly developed D3R antagonists in the animal models of OUD. These new drug candidates may also potentiate the analgesic effects of clinically used opioids, making them attractive as adjunctive medications for pain management and treatment of OUD.

SUBMITTER: Galaj E

PROVIDER: S-EPMC7252042 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges.

Galaj Ewa E Newman Amy Hauck AH Xi Zheng-Xiong ZX

Neuroscience and biobehavioral reviews 20200503

Opioid abuse and related overdose deaths continue to rise in the United States, contributing to the current national opioid crisis. Although several opioid-based pharmacotherapies are available (e.g., methadone, buprenorphine, naloxone), they show limited effectiveness in long-term relapse prevention. In response to the opioid crisis, the National Institute on Drug Abuse proposed a list of pharmacological targets of highest priority for medication development for the treatment of opioid use diso ...[more]

PMID: 32376243

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Project description:Background and aimsAs treatment for opioid use disorder (OUD) expands within general healthcare settings such as primary care, mechanisms to facilitate decision-making processes are increasingly necessary. Decision aids have the capacity to bolster existing resources in diverse treatment settings by increasing knowledge of treatment options and facilitating shared decision making. The aim of this study is to develop and test a patient decision aid for medication treatment for opioid use disorder (PtDA-MOUD) that assists individuals with OUD in making informed decisions about treatment at the time of initial clinical visit. Use of the PtDA-MOUD will be further tested in diverse treatment settings within the California Hub and Spoke System developed under the SAMHSA State Targeted Response to the Opioid Crisis grants.MethodsThe PtDA-MOUD was iteratively developed with input from a scientific expert panel and both patient and provider focus groups, incorporating International Patient Decision Aid Standards. Thirty-six patients with OUD entering treatment pilot tested the PtDA and completed assessments, and results from clinical records were compared with matched controls who did not receive the PtDA. A clinical profile based on assessment data was created for use within the clinical visit.ResultsThe developed decision aid provides information on MOUD and captures patient characteristics relevant to medication treatment decisions. Feedback indicated that the PtDA-MOUD was feasible to implement and useful. Though the small sample size limited the ability to detect significant differences (p > .05), a greater number of individuals who reviewed the PtDA (37%) were inducted on MOUD than controls (11%) and received MOUD for more days (M = 14.0, SD = 24.7) than controls (M = 8.4; SD = 22.5). Moreover, the difference in means for days receiving MOUD had an approximately medium effect size (r = 0.25).ConclusionsPatient perceptions of the decision aid were favorable and it showed promise as a tool in the OUD treatment process. Pilot testing results suggested preliminary positive effects on MOUD initiation. Future phases of this study will further investigate the usefulness of this tool. ClinicalTrials.govIdentifier:NCT03394261.

Project description:Objective(s)To understand how contraception method use differed between women prescribed and not prescribed medications for opioid use disorder (MOUD) among commercially-insured and Medicaid-insured women.Study designIBM Watson Health MarketScan Commercial Claims and Encounters database and the Multi-State Medicaid database were used to calculate the (1) crude prevalence, and (2) adjusted odds ratios (adjusted for demographic characteristics) of using long-acting reversible or short-acting hormonal contraception methods or female sterilization compared with none of these methods (no method) in 2018 by MOUD status among women with OUD, aged 20 to 49 years, with continuous health insurance coverage through commercial insurance or Medicaid for ≥6 years. Claims data was used to define contraception use. Fisher exact test or χ2 test with a P-value ≤ 0.0001, based on the Holm-Bonferroni method, and 95% confidence intervals were used to determine statistically significant differences for prevalence estimates and adjusted odds ratios, respectively.ResultsOnly 41% of commercially-insured and Medicaid-insured women with OUD were prescribed MOUD. Medicaid-insured women with OUD prescribed MOUD had a significantly lower crude prevalence of using no method (71.1% vs 79.0%) and higher odds of using female sterilization (aOR, 1.33; 95% CI: 1.06-1.67 vs no method) than those not prescribed MOUD. Among commercially-insured women there were no differences in contraceptive use by MOUD status and 66% used no method.ConclusionsAmong women with ≥ 6 years of continuous insurance coverage, contraceptive use differed by MOUD status and insurance. Prescribing MOUD for women with OUD can be improved to ensure quality care.ImplicationsOnly two in five women with OUD had evidence of being prescribed MOUD, and majority did not use prescription contraception or female sterilization. Our findings support opportunities to improve prescribing for MOUD and integrate contraception and MOUD services to improve clinical care among women with OUD.

Project description:AimThis report examined naturalistic opioid use outcomes and utilization of medications for opioid use disorder (MOUD) 36 weeks post-randomization in the National Drug Abuse Treatment Clinical Trials Network (CTN) Extended-Release Naltrexone (XR-NTX) versus Buprenorphine-Naloxone (BUP-NX) for Opioid Treatment trial (CTN-0051, X:BOT).DesignX:BOT was a multisite, randomized, 24-week comparative effectiveness trial of BUP-NX (N = 287) and XR-NTX (N = 283). Study medications were discontinued following treatment completion, relapse, or dropout. Participants were encouraged to continue MOUD. This report examined opioid use outcomes in 428 (75%) of the 570 participants who attended the 36-week follow-up visit.Setting and participantsAdults with opioid use disorder recruited from 8 community treatment programs across the United States.MeasurementsOutcomes included medication status (on/off MOUD), type of MOUD (BUP-NX, XR-NTX, or methadone), abstinence from non-prescribed opioids, opioid use days, relapse, and other substance use 30 days prior to the 36-week visit. Relapse was defined as opioid use for 4 consecutive weeks or 7 consecutive days in the past month. Baseline and clinical variables included opioid use severity, intravenous drug use, study medication assignment, and induction status.FindingsOf the 428 participants who completed the 36-week visit, 225 (53%) of participants were receiving MOUD and 203 (47%) were not. Compared to those off medication, participants on medication had fewer opioid use days (4.4 days (SD 9.0) versus 9.8 days (SD 12.1)), fewer met relapse criteria (37 (16.4%) versus 79 (38.9%)), and reported less stimulant use (34 (15.2%) versus 56 (27.7%)) and sedative use (14 (6.3%) versus 31 (15.3%)). There was no difference in abstinence rates between those on or off MOUD. A greater proportion of participants on XR-NTX (47 (53.4%) of 88 participants) were abstinent from non-prescribed opioids compared to those on buprenorphine (28 (23.3%) of 120 participants).ConclusionsNaturalistic outcomes data showed that despite potential barriers to continuing treatment in the community, about half of individuals were on opioid use disorder pharmacotherapy at follow-up and those on medication generally had better outcomes. Future research should explore barriers and facilitators to treatment retention in community settings; and developing interventions tailored to improve treatment engagement and adherence.

Dataset Information

Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges.

Publications

Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges.

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