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Biological Psychiatry Jan 2020Opioid use disorder (OUD) is a chronic, relapsing condition, often associated with legal, interpersonal, and employment problems. Medications demonstrated to be... (Review)
Review
Opioid use disorder (OUD) is a chronic, relapsing condition, often associated with legal, interpersonal, and employment problems. Medications demonstrated to be effective for OUD are methadone (a full opioid agonist), buprenorphine (a partial agonist), and naltrexone (an opioid antagonist). Methadone and buprenorphine act by suppressing opioid withdrawal symptoms and attenuating the effects of other opioids. Naltrexone blocks the effects of opioid agonists. Oral methadone has the strongest evidence for effectiveness. Longer duration of treatment allows restoration of social connections and is associated with better outcomes. Treatments for OUD may be limited by poor adherence to treatment recommendations and by high rates of relapse and increased risk of overdose after leaving treatment. Treatment with methadone and buprenorphine has the additional risk of diversion and misuse of medication. New depot and implant formulations of buprenorphine and naltrexone have been developed to address issues of safety and problems of poor treatment adherence. For people with OUD who do not respond to these treatments, there is accumulating evidence for supervised injectable opioid treatment (prescribing pharmaceutical heroin). Another medication mode of minimizing risk of overdose is take-home naloxone. Naloxone is an opioid antagonist used to reverse opioid overdose, and take-home naloxone programs aim to prevent fatal overdose. All medication-assisted treatment is limited by lack of access and by stigma. In seeking to stem the rising toll from OUD, expanding access to approved treatment such as methadone, for which there remains the best evidence of efficacy, may be the most useful approach.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 31420089
DOI: 10.1016/j.biopsych.2019.06.020 -
Addiction (Abingdon, England) Sep 2022Appropriate clinical management of opioid withdrawal is a crucial bridge to long-term treatment for opioid use disorder (OUD), because it is a high-risk time for... (Review)
Review
Appropriate clinical management of opioid withdrawal is a crucial bridge to long-term treatment for opioid use disorder (OUD), because it is a high-risk time for potential opioid overdose and relapse. We provide a narrative review of evidence-based opioid withdrawal management strategies applicable to a variety of treatment settings and geographies. The goals of opioid withdrawal management include relieving suffering associated with withdrawal, providing appropriate diagnosis and screening, engaging patients in initiation of OUD treatment, and using harm reduction strategies, all guided by a patient-centered approach to care. In addition, we discuss complex cases, relapse prevention strategies, and new developments in opioid withdrawal management.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Secondary Prevention; Substance Withdrawal Syndrome
PubMed: 35112746
DOI: 10.1111/add.15818 -
The Alkaloids. Chemistry and Biology 2021This chapter provides a short overview of the history of morphine since it's isolation by Sertürner in 1805. The biosynthesis of the title alkaloid as well as all total... (Review)
Review
This chapter provides a short overview of the history of morphine since it's isolation by Sertürner in 1805. The biosynthesis of the title alkaloid as well as all total and formal syntheses of morphine and codeine published after 1996 are discussed in detail. The last section of this chapter provides a detailed overview of medicinally relevant derivatives of the title alkaloid.
Topics: Alkaloids; Biology; Codeine; Morphine
PubMed: 34565506
DOI: 10.1016/bs.alkal.2021.04.001 -
The Medical Clinics of North America Jul 2020The diagnosis of opioid use disorder (OUD) is often overlooked or inadequately managed during the inpatient admission. When recognized, a common strategy is opioid... (Review)
Review
The diagnosis of opioid use disorder (OUD) is often overlooked or inadequately managed during the inpatient admission. When recognized, a common strategy is opioid detoxification, an approach that is often ineffective and can be potentially dangerous because of loss of tolerance and subsequent risk for overdose. Medication for addiction treatment (MAT), including methadone and buprenorphine, is effective and can be dispensed in the hospital for both opioid withdrawal and initiation of maintenance treatment. Hospitalists should be knowledgeable about diagnosing and managing patients with OUD, including how to manage acute pain or MAT during the perioperative setting.
Topics: Analgesics, Opioid; Buprenorphine; Harm Reduction; Hospitalization; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Education as Topic
PubMed: 32505261
DOI: 10.1016/j.mcna.2020.03.003 -
JAMA Psychiatry Jul 2021Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment.
IMPORTANCE
Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment.
OBJECTIVE
To assess the cost-effectiveness of OUD treatments and association of these treatments with outcomes in the US.
DESIGN AND SETTING
This model-based cost-effectiveness analysis included a US population with OUD.
INTERVENTIONS
Medication-assisted treatment (MAT) with buprenorphine, methadone, or injectable extended-release naltrexone; psychotherapy (beyond standard counseling); overdose education and naloxone distribution (OEND); and contingency management (CM).
MAIN OUTCOMES AND MEASURES
Fatal and nonfatal overdoses and deaths throughout 5 years, discounted lifetime quality-adjusted life-years (QALYs), and costs.
RESULTS
In the base case, in the absence of treatment, 42 717 overdoses (4132 fatal, 38 585 nonfatal) and 12 660 deaths were estimated to occur in a cohort of 100 000 patients over 5 years, and 11.58 discounted lifetime QALYs were estimated to be experienced per person. An estimated reduction in overdoses was associated with MAT with methadone (10.7%), MAT with buprenorphine or naltrexone (22.0%), and when combined with CM and psychotherapy (range, 21.0%-31.4%). Estimated deceased deaths were associated with MAT with methadone (6%), MAT with buprenorphine or naltrexone (13.9%), and when combined with CM, OEND, and psychotherapy (16.9%). MAT yielded discounted gains of 1.02 to 1.07 QALYs per person. Including only health care sector costs, methadone cost $16 000/QALY gained compared with no treatment, followed by methadone with OEND ($22 000/QALY gained), then by buprenorphine with OEND and CM ($42 000/QALY gained), and then by buprenorphine with OEND, CM, and psychotherapy ($250 000/QALY gained). MAT with naltrexone was dominated by other treatment alternatives. When criminal justice costs were included, all forms of MAT (with buprenorphine, methadone, and naltrexone) were associated with cost savings compared with no treatment, yielding savings of $25 000 to $105 000 in lifetime costs per person. The largest cost savings were associated with methadone plus CM. Results were qualitatively unchanged over a wide range of sensitivity analyses. An analysis using demographic and cost data for Veterans Health Administration patients yielded similar findings.
CONCLUSIONS AND RELEVANCE
In this cost-effectiveness analysis, expanded access to MAT, combined with OEND and CM, was associated with cost-saving reductions in morbidity and mortality from OUD. Lack of widespread MAT availability limits access to a cost-saving medical intervention that reduces morbidity and mortality from OUD. Opioid overdoses in the US likely reached a record high in 2020 because of COVID-19 increasing substance use, exacerbating stress and social isolation, and interfering with opioid treatment. It is essential to understand the cost-effectiveness of alternative forms of MAT to treat OUD.
Topics: Adult; Buprenorphine; Combined Modality Therapy; Cost-Benefit Analysis; Delayed-Action Preparations; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy; Treatment Outcome
PubMed: 33787832
DOI: 10.1001/jamapsychiatry.2021.0247 -
Nature Communications Oct 2022The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms...
The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAc) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAc) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAc neurons impairs reward seeking behavior, while silencing of NAc or NAc→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.
Topics: Mice; Animals; Nucleus Accumbens; Reward; Ventral Tegmental Area; Dopaminergic Neurons; Opiate Alkaloids
PubMed: 36271048
DOI: 10.1038/s41467-022-33843-3 -
World Journal of Surgery Apr 2022The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown.
OBJECTIVE
The present systematic review and meta-analysis aims to compare the efficacy of different analgesic modalities trialled in AP.
METHODS
A systematic search of PubMed, MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science conducted up until June 2021, identified all randomised control trials (RCTs) comparing analgesic modalities in AP. A pooled analysis was undertaken of the improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2.
RESULTS
Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), metamizole, local anaesthetic, epidural, paracetamol, and placebo. Across all modalities, the pooled VAS scores showed global improvement from baseline to day 2. Epidural analgesia appears to provide the greatest improvement in VAS within the first 24 h but is equivalent to opiates by 48 h. Within 24 h, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant statistical and methodological heterogeneity in pain-relief reporting.
CONCLUSIONS
There is remarkable paucity of level 1 evidence to guide pain management in AP with small datasets per study. Epidural administration appears effective within the first 24 h of AP although infrequently used and featured in only a single RCT. NSAIDs are an effective opiate sparing alternative during the first 24 h.
Topics: Analgesia; Analgesics; Analgesics, Opioid; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Humans; Opiate Alkaloids; Pain; Pain Management; Pancreatitis; Randomized Controlled Trials as Topic
PubMed: 34994837
DOI: 10.1007/s00268-021-06420-w -
Emergency Medicine Clinics of North... Aug 2021In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic... (Review)
Review
In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Kratom, a plant occasionally used for opiate detoxification, along with the sedatives etizolam and phenibut, will be discussed. Lastly, this article discusses the phenethylamines and marijuana.
Topics: Analgesics, Opioid; Buprenorphine; Cannabinoids; Designer Drugs; Drug Overdose; Fentanyl; Humans; Hypnotics and Sedatives; Illicit Drugs; Loperamide; Mitragyna; Naloxone; Narcotic Antagonists; Phenethylamines; Substance-Related Disorders
PubMed: 34215409
DOI: 10.1016/j.emc.2021.04.013 -
The Annals of Pharmacotherapy Nov 2019The incidence of opioid allergy cross-reactivity in hospitalized patients with historical opioid allergies remains unknown. The purpose of this study was to...
The incidence of opioid allergy cross-reactivity in hospitalized patients with historical opioid allergies remains unknown. The purpose of this study was to characterize the incidence of newly suspected IgE-mediated reactions (IMRs) based on clinical criteria among patients with a chart-documented opioid allergy and to assess clinician perceptions of opioid allergies. This retrospective cohort study was conducted in hospitalized adults with a historically documented opioid allergy who received a subsequent opioid. The primary outcome was the incidence of allergic cross-reactivity between clinical and chemical opioid classes in patients with historical IMRs (H-IMRs) identified by clinical criteria, ICD-9 diagnosis codes, or allergic reaction treatment. Secondary outcomes included the incidence of opioid intolerances incorrectly documented as allergies and a survey to clinicians to assess the impact of opiate warnings on prescribing practices. A total of 499 patients with historical opioid allergies were included. H-IMR to an opioid of any class was not significantly associated with IMR cross-reactivity to the same or any other class, with cross-reactivity rates ranging from 0% to 6.7%. Of the historical chart-documented allergies, 249 reactions (50%) were determined to be intolerances. A total of 461 (92.5%) patients successfully tolerated readministration of opioids despite a chart-documented allergy, and 8 (1.6%) patients developed possible IMR (7 pruritus, 1 possible anaphylaxis). Survey results (n = 54) indicated that opiate allergy warnings were neutral or unlikely to change opiate prescribing. The risk of IMRs caused by opioids is low in patients with H-IMRs to opioids. Opioid allergy documentations may propagate alert fatigue and unwarranted prescribing changes.
Topics: Analgesics, Opioid; Drug Hypersensitivity; Female; Humans; Incidence; Male; Middle Aged; Perception; Retrospective Studies
PubMed: 31253049
DOI: 10.1177/1060028019860521