Behavioral and Accumbal Responses During an Affective Go/No-Go Task Predict Adherence to Injectable Naltrexone Treatment in Opioid Use Disorder.
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ABSTRACT:
SUBMITTER: Shi Z
PROVIDER: S-EPMC6403086 | biostudies-other | 2019 Mar
REPOSITORIES: biostudies-other
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Project description:AIMS:To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol® ), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR-NTX; (2) what are adherence rates to XR-NTX; and (3) does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined. METHODS:We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included. RESULTS:We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification. CONCLUSIONS:Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.
| S-EPMC5993595 | biostudies-literature
Project description:Compared to female major depressive disorder (MDD), male MDD often receives less attention. However, research is warranted since there are significant sex differences in the clinical presentation of MDD and a higher rate of suicide in depressed men. To the best of our knowledge, this is the first functional magnetic resonance imaging (fMRI) study with a large sample addressing putative sex differences in MDD during adolescence, a period when one of the most robust findings in psychiatric epidemiology emerges; that females are twice as likely to suffer from MDD than males. Twenty-four depressed and 10 healthy male adolescents, together with 82 depressed and 24 healthy female adolescents, aged 11-18 years, undertook an affective go/no-go task during fMRI acquisition. In response to sad relative to neutral distractors, significant sex differences (in the supramarginal gyrus) and group-by-sex interactions (in the supramarginal gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to the healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with a significant group-by-age interaction in connectivity. Future research may consider altered developmental trajectories and the possible implications of sex-specific treatment and prevention strategies for MDD.
| S-EPMC5504124 | biostudies-literature
Project description:We investigated prescribing patterns for four opioid use disorder (OUD) medications: 1) injectable naltrexone, 2) oral naltrexone, 3) sublingual or oralmucosal buprenorphine/naloxone, and 4) sublingual buprenorphine as well as transdermal buprenorphine (which is approved for treating pain, but not OUD) in a nationally representative claims-based database (Truven Health MarketScan®) of commercially insured individuals in the United States. We calculated the prevalence of OUD in the database for each year from 2010 to 2014 and the proportion of diagnosed patient months on OUD medication. We compared characteristics of individuals diagnosed with OUD who did and did not receive these medications with bivariate descriptive statistics. Finally, we fit a Cox proportional hazards model of time to discontinuation of therapy as a function of therapy type, controlling for relevant confounders. From 2010 to 2014, the proportion of commercially insured individuals diagnosed with OUD grew by fourfold (0.12% to 0.48%), but the proportion of diagnosed patient-months on medication decreased from 25% in 2010 (0.05% injectable naltrexone, 0.4% oral naltrexone, 23.1% sublingual or oralmucosal buprenorphine/naloxone, 1.5% sublingual buprenorphine, and 0% transdermal buprenorphine) to 16% in 2014 (0.2% injectable naltrexone, 0.4% oral naltrexone, 13.8% sublingual or oralmucosal buprenorphine/naloxone, 1.4% sublingual buprenorphine, and 0.3% transdermal buprenorphine). Individuals who received medication therapy were more likely to be male, younger, and have an additional substance use disorder compared with those diagnosed with OUD who did not receive medication therapy. Those prescribed injectable naltrexone were more often male, younger, and diagnosed with additional substance use disorders compared with those prescribed other medications for opioid use disorder (MOUDs). At 30 days after initiation, 52% for individuals treated with injectable naltrexone, 70% for individuals treated with oral naltrexone, 31% for individuals treated with sublingual or oralmucosal buprenorphine/naloxone, 58% for individuals treated with sublingual buprenorphine, and 51% for individuals treated with transdermal buprenorphine discontinued treatment. In the Cox proportional hazard model, use of injectable naltrexone, oral naltrexone, sublingual buprenorphine, and transdermal buprenorphine were all associated with significantly greater hazard of discontinuing therapy beginning >30days after MOUD initiation (HR=2.17, 2.54, 1.15, and 2.21, respectively, 95% CIs 2.04-2.30, 2.45-2.64, 1.10-1.19, and 2.11-2.33), compared with the use of sublingual or oralmucosal buprenorphine/naloxone. This analysis demonstrates that the use of evidence-based medication therapies has not kept pace with increases in OUD diagnoses in commercially insured populations in the United States. Among those who have been treated, discontinuation rates >30days after initiation are high. The proportion treated with injectable naltrexone, oral naltrexone, and transdermal buprenorphine grew over time but remains small, and the discontinuation rates are higher among those treated with these medications compared with those treated with sublingual or oralmucosal buprenorphine/naloxone. In the face of the opioid overdose and addiction crisis, new efforts are needed at the provider, health system, and policy levels so that MOUD availability and uptake keep pace with new OUD diagnoses and OUD treatment discontinuation is minimized.
| S-EPMC5750108 | biostudies-literature
Project description: Not available
| S-EPMC9367130 | biostudies-literature
Project description:BACKGROUND:The theoretical benefits of naltrexone as a treatment for opioid use disorder (e.g., safety, non-addictive, low risk of diversion) stand in sharp contrast to its disappointing record on retention in most samples. The relationship of uncomfortable physical and dysphoric symptoms to retention on naltrexone is a controversial and under-studied issue. METHODS:Using data from a randomized controlled trial of voucher-based contingency management and support from a significant other to enhance retention on oral naltrexone, we compared self-reported somatic and dysphoric symptoms, measured weekly, for individuals who were retained on naltrexone through the 12-week trial (n?=?50) versus those who dropped out (n?=?70). RESULTS:There were no differences between participants who completed treatment and those who dropped out on multiple baseline characteristics, including somatic or affective symptoms prior to treatment. However, whether analyzed cross-sectionally or over time, participants who dropped out consistently reported higher rates of somatic symptoms, particularly difficulty sleeping, as well as affective symptoms, including multiple indicators of depression, anxiety, and anhedonia. CONCLUSIONS:Although the smaller group of participants who were retained on oral naltrexone for 12 weeks reported decreasing physical and affective discomfort over time, there was substantial evidence that those who dropped out experienced continued and significant levels of distress. Individuals who report physical or affective distress while taking naltrexone may be at higher risk of dropout.
| S-EPMC6203294 | biostudies-literature
Project description:BackgroundWhile the opiate antagonist, naltrexone, is approved for treating alcohol use disorder (AUD), not everyone who receives the medication benefits from it. This study evaluated whether the OPRM1 SNP rs1799971 interacts with the dopamine transporter gene DAT1/SLC6A3 VNTR rs28363170 or the catechol-O-methyltransferase (COMT) gene SNP rs4680 in predicting naltrexone response.MethodsIndividuals who met DSM-IV alcohol dependence were randomly assigned to naltrexone (50 mg/d) or placebo based on their OPRM1 genotype (75 G-allele carriers and 77 A-allele homozygotes) and also genotyped for DAT1 VNTR (9 vs. 10 repeats) or COMT SNP (val/val vs. met carriers). Heavy drinking days (%HDD) were evaluated over 16 weeks and at the end of treatment. Effect sizes (d) for naltrexone response were calculated based on genotypes.ResultsNaltrexone, relative to placebo, significantly reduced %HDD among OPRM1 G carriers who also had DAT1 10/10 (p = 0.021, d = 0.72) or COMT val/val genotypes (p = 0.05, d = 0.80), and to a lesser degree in those OPRM1 A homozygotes who were also DAT1 9-repeat carriers (p = 0.09, d = 0.70) or COMT met carriers (p = 0.03, d = 0.63). All other genotype combinations showed no differential response to naltrexone. Diarrhea/abdominal pain was more prominent in OPRM1 A homozygotes who were also DAT 9 or COMT met carriers.ConclusionsThese results suggest that individuals with AUD with a more opioid-responsive genotype (OPRM1 G carriers) respond better to naltrexone if they have genotypes indicating normal/less dopamine tone (DAT1 10,10 or COMT val,val), while those with a less responsive opioid-responsive genotype (OPRM1 A homozygotes) respond better to naltrexone if they have genotypes indicating greater dopamine tone (DAT1 9-repeat or COMT met carriers). These results could lead to more personalized AUD treatments.
| S-EPMC8080431 | biostudies-literature
Project description:The ability to exert self-control in the face of appetitive, alluring cues is a critical component of healthy development. The development of behavioral measures that use disease-relevant stimuli can greatly improve our understanding of cue-specific impairments in self-control. To produce such a tool relevant to the study of eating and weight disorders, we modified the traditional go/no-go task to include food and non-food targets. To confirm that performance on this new task was consistent with other go/no-go tasks, it was given to 147 healthy, normal weight volunteers between the ages of 5 and 30. High-resolution photos of food or toys were used as the target and nontarget stimuli. Consistent with expectations, overall improvements in accuracy were seen from childhood to adulthood. Participants responded more quickly and made more commission errors to food cues compared to nonfood cues (F(1,140)=21.76, P<0.001), although no behavioral differences were seen between low- and high-calorie food cues for this non-obese, healthy developmental sample. This novel food-specific go/no-go task may be used to track the development of self-control in the context of food cues and to evaluate deviations or deficits in the development of this ability in individuals at risk for eating problem behaviors and disorders.
| S-EPMC4128315 | biostudies-literature
Project description:Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.
| S-EPMC10044490 | biostudies-literature
Project description:BackgroundOral antiretroviral therapy (ART) has been effective at reducing mortality rates of people with HIV. However, despite its effectiveness, people who use drugs face barriers to maintaining ART adherence. Receipt of opioid agonist treatment, in the context of HIV care, is associated with medication adherence and decreased HIV viral loads. Recent pharmacological advancements have led to the development of novel long-acting, injectable, medications for both HIV (cabotegravir co-administered with rilpivirine) and OUD (extended-release buprenorphine). These therapies have the potential to dramatically improve adherence by eliminating the need for daily pill-taking. Despite the extensive evidence base supporting long-acting injectable medications for both HIV and OUD, and clinical guidelines supporting integrated care provision, currently little is known about how these medications may be optimally delivered to this population. This paper presents the study design for the development of a clinical protocol to guide the delivery of combined treatment for HIV and OUD using long-acting injectable medications.MethodsThe study aims are to: (1) develop a clinical protocol to guide the delivery of combined LAI for HIV and OUD by conducting in-depth interviews with prospective patients, clinical content experts, and other key stakeholders; and (2) conduct This single group, open pilot trial protocol to assess feasibility, acceptability, and safety among patients diagnosed with HIV and OUD. Throughout all phases of the study, information on patient-, provider-, and organizational-level variables will be collected to inform future implementation.DiscussionFindings from this study will inform the development of a future study to conduct a fully-powered Hybrid Type 1 Effectiveness-Implementation design.
| S-EPMC10576282 | biostudies-literature
Project description:Introduction: Despite widespread recognition of the opioid crisis, opioid overdose remains a common reason for Emergency Department (ED) utilization. Treatment for these patients after stabilization often involves the provision of information for outpatient treatment options. Ideally, an ED visit for overdose would present an opportunity to start treatment for opioid use disorder (OUD) immediately. Although widely recognized as effective, opioid agonist therapy with methadone and buprenorphine commonly referred to as "medication-assisted therapy" but more correctly as "medication for addiction treatment" (MAT), can be difficult to access even for motivated individuals due to shortages of prescribers and treatment programs. Moreover, opioid agonist therapy may not be appropriate for all patients, as many patients who present after overdose are not opioid dependent. More treatment options are required to successfully match patients with diverse needs to an optimal treatment plan in order to avoid relapse. Naltrexone, a long-acting opioid antagonist, available orally and as a monthly extended-release intramuscular injection, may represent another treatment option. Methods: We conducted a literature search of MEDLINE and PubMed. We aimed to capture references related to naltrexone and is use as MAT for OUD, as well as manuscripts that discussed naltrexone in comparison toother agents used for MAT, opioid detoxification, and naltrexone metabolism. Our initial search logic returned a total of 618 articles. Following individual evaluation for relevance, we selected 65 for in-depthreview. Manuscripts meeting criteria were examined for citations meriting further review, leading to the addition of 30 manuscripts Conclusions: Here, we review the pharmacology of naltrexone as it relates to OUD, its history of use, and highlight recent studies and new approaches for use of the drug as MAT including its potential initiation after ED visit for opioid overdose.
| S-EPMC6908461 | biostudies-literature