Journal of Addiction Medicine最新文献

The concept of treatment-refractory addiction (TRA), while relatively new to the addiction field, is a well-established concept in other areas of medicine and psychiatry. Recent commentaries have highlighted the need for clearer conceptualization and definition of TRA. This commentary argues that conceptual frameworks established in other psychiatric domains (eg, depression, schizophrenia, obsessive-compulsive disorder) can and should inform the development of criteria and strategies for identifying and addressing TRA in substance use disorders (SUDs). Central to this effort is the recognition that treatment response variability is the norm rather than the exception in SUD care. Conceptualizations and definitions of TRA should seek to distinguish true refractoriness from suboptimal or incomplete treatment exposure, which can arise from inadequate treatment exposure or adherence, and consider whether nonresponse is present from the start (primary refractoriness) or emerges over time (secondary refractoriness). Advanced analytic methods, including unsupervised clustering, offer opportunities to characterize heterogeneity in treatment outcomes in aggregate or over time, identify patient subgroups that do not benefit from standard therapies, and explore underlying mechanisms of nonresponse. By integrating lessons learned from other psychiatric disorders, addiction scientists can develop more precise definitions of TRA, which will ultimately inform the development of diagnostic/prognostic frameworks, and targeted interventions.

Objectives: Medetomidine, a potent veterinary α2-adrenergic agonist, has emerged as an adulterant in the illicit fentanyl supply in Philadelphia, PA. Accompanying this change, a severe withdrawal syndrome, distinct from opioid and more comparable to dexmedetomidine withdrawal, emerged. We describe it.

Methods: A multicenter case series is described across 3 hospital systems in Philadelphia between September 2024 and April 2025. The cohort included patients who reported opioids as the primary drug of choice, who presented with opioid withdrawal complicated by severe sympathetic activation and required hospitalization. Data extraction from the electronic health record included demographics, clinical outcomes, and confirmatory toxicology in a subset.

Results: Two hundred nine patients met the inclusion criteria; the median age was 38 years and 29% were female. Intensive care unit (ICU) admission occurred in 77.5%, with 20.1% requiring intubation. Symptoms were often refractory to traditional opioid withdrawal management, and 73.7% received dexmedetomidine infusion. In the cohort subset with toxicology testing (n=43), 100% had fentanyl and medetomidine metabolites, while xylazine metabolites were not always present (24, 55.8%). Severe complications included encephalopathy (35.4%), myocardial injury (28.7%), and rarely seizures (5%). Patients suffered from severe withdrawal, with a median maximum recorded Clinical Opiate Withdrawal Score (COWS) score of 23.

Conclusions: This study describes individuals experiencing severe withdrawal, temporally associated with medetomidine-adulterated fentanyl exposure. Clinicians should be alert to the limitations of standard withdrawal protocols for fentanyl or opioids and the need for aggressive α2-agonist therapies, such as dexmedetomidine. As medetomidine continues to spread in the illicit drug supply, adapting clinical and public health responses will be critical.

Objectives: This paper describes how artificial intelligence (AI) was used to analyze meeting minutes from community coalitions participating in the HEALing Communities Study. We examined how often coalitions discussed stigma when selecting evidence-based practices (EBPs), variations in stigma-related discussions across coalitions, how these discussions addressed race, ethnicity, and racial inequity, and whether the frequency of stigma discussions was associated with the proportion of minoritized populations in each community.

Methods: We used Natural Language Processing, Machine Learning, and Large Language Models, employing ChatGPT Enterprise to code data, ensuring data security and privacy compliance with the General Data Protection Regulation and HIPAA.

Results: Community coalitions varied in the extent to which they discussed stigma during meetings focused on EBPs to reduce overdose deaths. Stigma was mentioned more frequently in the context of medication for opioid use disorder compared with other EBPs. As the percentage of racial/ethnic minority populations increased in a county, so did the strength of the association between discussions of EBPs and stigma. Counties with a greater proportion of racial/ethnic minority populations were more likely to integrate discussions of EBPs with stigma-related issues. Specifically, discussions about stigma were ~57% more likely to occur when racial or ethnic disparities were mentioned, compared with when they were not (odds ratio=1.57; 95% CI: 1.22, 2.03).

Conclusions: The paper highlights the potential for integrating AI-human collaboration into community-engaged research, particularly in leveraging qualitative data such as meeting minutes. It shows how AI can be used in real-time to enhance community-based research.

Background: Fentanyl is a rising cause of morbidity and mortality in the United States, affecting neonates exposed in utero. Xylazine, an alpha-2 receptor agonist, is a non-narcotic sedative that is becoming an increasingly common adulterant. There are case reports describing the clinical manifestations of xylazine exposure and toxicity in adult populations; however, cases involving neonatal populations are not described in the literature. Limitations of toxicology analyses for neonates cause delays in the identification and treatment of affected patients.

Case summary: We present the case of a term neonate who presented to the neonatal intensive care unit with a strong foul-smelling odor, diffuse rash, hypertonicity, irritability, and inconsolability. This case describes additional symptoms that presented over the subsequent 120 hours of life, including sustained bradycardia, significant peripheral vasoconstriction, and focalization of odor to breath, urine, feces, and umbilical stump. Mass spectroscopy toxicology of the neonate's serum confirmed the presence of methamphetamine, fentanyl, multiple fentanyl metabolites, and xylazine. Management strategies are discussed, including the role of alpha-2 receptor agonists in treating withdrawal.

Clinical significance: This case report presents clinical manifestations of xylazine toxicity and withdrawal in neonatal populations and highlights the need for additional attention on the effects of adulterants to improve management strategies. There is a need for improved toxicology testing to identify affected populations in a timely manner.

Objectives: Approximately 3 million U.S. children live with a parent with an illicit or prescription substance use disorder (SUD) and may be at risk of witnessing an overdose. Parents with SUD offer valuable perspectives on how to facilitate conversations around overdose response. Our aim was to assess attitudes of parents with SUD towards discussing naloxone with their children.

Methods: Parents with SUD were recruited from SUD treatment programs, social media, and a research website to participate in semistructured virtual focus groups facilitated by peers with lived experience of SUD while parenting. The interview guide was informed by study teams' clinical experiences. We used an inductive thematic analysis approach; transcripts were double-coded.

Results: Fifteen parents identifying as mothers participated in 4 focus groups. Four themes were identified. First, most mothers had not discussed naloxone use with their children, yet felt it was important to prepare them to respond to potential overdoses. Second, mothers highlighted that normalizing naloxone education through comparisons to other emergency responses may reduce stigma and expand learning opportunities. Third, mothers noted that overdose response involves physical, cognitive, and emotional processing skills that are acquired at different stages of child development. Fourth, mothers shared that naloxone discussions often require disclosing their own substance use, which was identified as a challenging conversation that mothers were variably ready to navigate.

Conclusions: Mothers with SUD believed their children would benefit from naloxone education. Supporting parents navigating their own SUD disclosure and identifying developmentally appropriate tools are important steps in devising education strategies.

Compulsive use of social media, when it becomes problematic, shares behavioral similarities with substance use disorders. Moreover, preliminary imaging studies have reported structural and functional brain deficits that overlap with those seen in drug addiction, supporting an addictive dimensional component underlying problematic use of social media. Current evidence is consistent with the hypothesis that excessive or maladaptive reliance on social media can trigger or exacerbate symptoms of depression and anxiety, particularly among young people, further perpetuating its use and expanding its potential adverse effects. To better understand the potential negative public health outcomes from social media, there is a pressing need for increased oversight of algorithms and business models, coupled with rigorous research to better identify the at-risk populations and understand its consequences. This could help develop evidence-based prevention and treatment interventions for those who may develop problematic use of social media.

When opioid therapy for chronic pain was first promulgated in the 1980s and 90s, it was thought that addiction would be rare, would occur only in high-risk individuals, and should not interfere with the continued treatment with opioids for patients without opioid use disorder. DSM-5 OUD criteria were used as a means of separating out patients who had developed disordered opioid use from those who had not. This compartmentalization encouraged prescribers to refer those patients diagnosed with an OUD to addiction treatment, but to continue the focus on treating pain for others. But this binary approach failed to recognize that when a patient with chronic pain is treated with long-term opioid therapy, opioid need for pain may be hard to distinguish from withdrawal. This arises from the interaction of pain relief with opioid reward, which changes the motivations for continued opioid use in ways not always obvious to patients or prescribers. In this article, we propose that a syndrome of dependence develops during continued opioid pain treatment that should be considered distinct from POUD. Recognition of a prescription opioid dependence syndrome (PODS) allows for a more nuanced approach to the treatment of failed opioid pain treatment, especially in cases where neither continued high-dose opioid pain treatment nor evidence-based addiction treatment is a good option. We believe that recognition of this syndrome is a necessary first step towards improving treatment for the millions of people struggling with pain and opioid use.

Objectives: Extended-release naltrexone and once-daily bupropion (NTX-BUP) reduced methamphetamine (MA) use in the Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-1, ADAPT-2) trials. Using a proof-of-concept machine learning technique, we created a classification rule using baseline characteristics to identify individuals who would benefit more from NTX-BUP than from placebo (NTX-BUP-preferred).

Methods: ADAPT-2 (double-blind randomized-controlled sequential parallel comparison design trial, n=147) and ADAPT-1 (open-label pilot study, n=37) were used as the training and validation data sets, respectively. Baseline characteristics were combined to create the classification rule, which was trained to predict the number of negative urine drug screens (UDS) during weeks 5 and 6 of the ADAPT-2 trial and optimized using the ADAPT-1 data set. ADAPT-2 placebo nonresponders rerandomized to NTX-BUP (n=80) were used as the test data set. The performance of the classification rule was assessed by the number of negative UDS during weeks 11 and 12 and the number of responders.

Results: NTX-BUP-preferred participants (who would obtain greater benefit from NTX-BUP than from placebo), when compared with all NTX-BUP participants in the test data set, had higher response rates (0.26 vs. 0.16) and number of negative UDS (1.09 vs. 0.76). Placebo-preferred participants (would obtain greater benefit from placebo than from NTX-BUP) had lower response rates to NTX-BUP (0.07 vs. 0.16) and number of negative UDS (0.46 vs. 0.76) compared with all NTX-BUP participants.

Conclusions: This is a proof-of-concept analysis that needs to establish generalizability. This classification rule could help improve treatment selection, clinicians' treatment decisions, and patient outcomes.

Objectives: The inpatient addiction medicine consult team at West Suburban Medical Center started administering long-acting injectable buprenorphine (LAIB) to hospitalized patients in response to low rates of patients continuing treatment with sublingual buprenorphine after discharge. The aims of this study are to understand patients' motivations to receive LAIB during hospitalization and their experiences with the medication after discharge.

Methods: We conducted semi-structured interviews with patients who received LAIB while hospitalized between August 2022 and April 2023. Inductive analysis was used to identify themes and develop the codebook. Two researchers independently coded each interview and refined the codebook with oversight from 2 senior members of the research team. After the coding team reviewed each interview together to arrive at a joint consensus, a third coder found concordance in a random sample of interviews. Finally, the entire research team met to discuss key themes.

Results: Eighteen participants were interviewed between March and May 2023. The following key themes emerged: (1) limited knowledge and access to LAIB before hospitalization, (2) the role of peer support specialists in deciding to start LAIB while hospitalized, (3) fears around an increasingly unpredictable drug supply and personal experience with overdose as motivations to receive LAIB, (4) benefits of LAIB in multiple areas of participants' lives, and (5) negative aspects of LAIB.

Conclusions: Our participants' overall positive experiences with hospital-administered LAIB should inform policymakers and payors to support the expansion of this model and the exploration of additional strategies to lower barriers to LAIB access.

Objectives: While treatment guidelines for opioid use disorder (OUD) are well-established, specific guidance for people who use fentanyl remains limited. This systematic review is the first to examine effectiveness and safety outcomes associated with opioid agonist therapy (OAT), specifically buprenorphine, methadone, and slow-release oral morphine, in this patient population.

Methods: Following PRISMA guidelines, we systematically searched EMBASE, Medline, PsycINFO, CENTRAL (all via Ovid), and Scopus from inception to April 2025 for studies reporting OAT for fentanyl-related OUD. Primary outcomes included OAT titration time, treatment retention, withdrawal symptoms, remission, nonprescribed fentanyl use, and mortality. Risk of bias was assessed using the Cochrane risk of bias tools. Results were synthesized narratively.

Results: We identified 180 studies for inclusion (sample sizes ranging from 1 to 150,000). Several reports described treatment success using novel strategies, including low-dose ("microdosing," Bernese method) and high-dose buprenorphine ("macrodosing"), and rapid high-dose methadone protocols that deviate from standard guidelines.

Conclusions: Emerging, yet primarily low-quality evidence suggests novel OAT induction strategies for fentanyl-related OUD are feasible and show a consistent direction toward positive clinical and safety outcomes. High-quality research specific to this population, comparing conventional to novel strategies, is needed.