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Journal of Clinical Psychology Dec 2023More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely...
IMPORTANCE
More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short-term and long-term differences in cardiac and mortality outcomes between MOUD.
OBJECTIVES
To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016-2022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (n = 40,938)-who were only prescribed methadone. (2) Buprenorphine cohort (n = 80,055)-who were only prescribed buprenorphine. (3) Naltrexone cohort (n = 5,738)-who were only prescribed naltrexone.
EXPOSURES
methadone, buprenorphine, or naltrexone.
MAIN OUTCOMES AND MEASURES
Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow-up time frames (1-month, 3-month, 6-month, 1-year, 3-year, and 5-year) by comparing propensity-score matched cohorts using Kaplan-Meier survival analysis.
RESULTS
Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity-score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1-month follow-up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04-1.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75-3.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21-1.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23-1.38), long QT syndrome (HR: 3.14, 95% CI: 2.76-3.58), death (HR: 1.50, 95% CI: 1.41-1.59).
CONCLUSIONS AND RELEVANCE
Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.
Topics: Humans; United States; Naltrexone; Buprenorphine; Methadone; Retrospective Studies; Opiate Substitution Treatment; Opioid-Related Disorders; Long QT Syndrome; Prescriptions
PubMed: 37584532
DOI: 10.1002/jclp.23582 -
Journal of Medicinal Chemistry Aug 2023Opioid addiction is a chronically relapsing disorder that causes critical public health problems. Currently, there is a lack of effective drug treatment. Herein, one...
Opioid addiction is a chronically relapsing disorder that causes critical public health problems. Currently, there is a lack of effective drug treatment. Herein, one cannabidiol derivative, , was discovered as an effective agent for treating morphine-induced addiction. In vitro, exhibited significantly improved anti-neuroinflammatory activity with lower toxicity. In vivo, ameliorated the morphine-induced withdrawal reaction, behavioral sensitization, and conditional position preference by inhibiting morphine-induced microglia activation and neuroinflammation. Target fishing for by activity-based protein profiling led to the identification of pyruvate kinase M2 (PKM2) as the target protein. bound to the protein-protein interface of the PKM2 dimer and promoted the tetramerization of PKM2. Moreover, exhibited an anti-neuroinflammatory effect by reversing the decrease of the PKM2 tetramer and inhibiting the nuclear translocation of PKM2. In summary, this study identified as a lead compound in targeting PKM2 to treat morphine-induced addiction.
Topics: Pyruvate Kinase; Cannabidiol; Protein Transport; Morphine Derivatives
PubMed: 37531582
DOI: 10.1021/acs.jmedchem.3c01029 -
Obstetrics and Gynecology Dec 2023Extended-release buprenorphine (XRB) may improve medication for opioid use disorder continuation among postpartum individuals. However, obstetric clinicians have...
BACKGROUND
Extended-release buprenorphine (XRB) may improve medication for opioid use disorder continuation among postpartum individuals. However, obstetric clinicians have relatively little experience with XRB. We describe two cases of XRB-related tissue necrosis in postpartum individuals to highlight recommended injection technique and management strategies for this rare complication.
CASES
One patient developed tissue necrosis after her initial injection. Her wound was expectantly managed. Another patient on long-term XRB developed tissue necrosis within 1 day of injection. General surgery excised the depot. Both instances were attributed to injection of XRB intradermally rather than subcutaneously. Both patients continued monthly XRB without recurrence, suggesting that this complication is not an allergy.
CONCLUSION
Clinicians should be able to prevent, recognize, and manage tissue necrosis, a rare complication of XRB injection.
Topics: Humans; Female; Buprenorphine; Delayed-Action Preparations; Opioid-Related Disorders; Opiate Substitution Treatment; Injections; Analgesics, Opioid; Narcotic Antagonists
PubMed: 37917935
DOI: 10.1097/AOG.0000000000005425 -
The American Journal on Addictions Nov 2023Medication for opioid use disorder (MOUD) in primary care includes a combination of medication, behavioral therapy, and/or other psychosocial services. This study...
BACKGROUND AND OBJECTIVES
Medication for opioid use disorder (MOUD) in primary care includes a combination of medication, behavioral therapy, and/or other psychosocial services. This study assessed rates of colocation between waivered prescribers and behavioral health clinicians across the United States to understand if rates varied by provider type and geographic indicators.
METHODS
Data from the DEA-Drug Addiction Treatment Act of 2000 provider list as of March 2022 and the National Plan and Provider Enumeration System's National Provider Identifier database were gathered, cleaned, and formatted in Stata. Data were geocoded with ESRI StreetMap® database and ArcGIS software. Covariates at individual, county, and state levels were examined and compared. Chi-square statistics and a mixed-effects logistic regression were analyzed.
RESULTS
The sample (N = 71, 292 prescribers) included physicians (64%), nurse practitioners (29%), and physician assistants (7%). About 48% of prescribers were colocated with a behavioral health clinician. Physicians were the least likely to be colocated (47%), but differences between provider types were modest. We observed significant geographic differences in provider colocation by provider type. Mixed effects logistic regression identified significant predictors of colocation at individual, county, and state levels.
DISCUSSION AND CONCLUSIONS
Optimally distributing the workforce providing MOUD is necessary to broadly ensure the provision of comprehensive MOUD care based on practice guidelines.
SCIENTIFIC SIGNIFICANCE
Less than half of all waivered prescribers, outside of hospitals, are colocated with behavioral health clinicians. Findings offer greater clarity on where integrated MOUD is occurring, among which types of providers, and where it needs to be expanded to increase MOUD uptake.
Topics: Humans; United States; Buprenorphine; Opioid-Related Disorders; Physicians; Psychiatry; Behavior Therapy; Opiate Substitution Treatment
PubMed: 37559344
DOI: 10.1111/ajad.13462 -
Journal of Pain & Palliative Care... Sep 2023
Topics: Humans; Morphine; Naloxone; Injections, Spinal
PubMed: 37314428
DOI: 10.1080/15360288.2023.2219666 -
BMC Psychiatry Dec 2023Number of opiate users worldwide has doubled over the past decade, but not all of them are diagnosed with opioid use disorder. We aimed to identify the prevalence and...
BACKGROUND
Number of opiate users worldwide has doubled over the past decade, but not all of them are diagnosed with opioid use disorder. We aimed to identify the prevalence and risk factors for OUD after ten years of follow-up.
METHODS
Among 8,500 chronic opiate users at Golestan Cohort Study baseline (2004-2008), we recalled a random sample of 451 subjects in 2017. We used three questionnaires: a questionnaire about current opiate use including type and route of use, the drug use disorder section of the Composite International Diagnostic Interview lifetime version, and the validated Kessler10 questionnaire. We defined opioid use disorder and its severity based on the DSM-5 criteria and used a cutoff of 12 on Kessler10 questionnaire to define psychological distress.
RESULTS
Mean age was 61.2 ± 6.6 years (84.7% males) and 58% were diagnosed with opioid use disorder. Starting opiate use at an early age and living in underprivileged conditions were risk factors of opioid use disorder. Individuals with opioid use disorder were twice likely to have psychological distress (OR = 2.25; 95%CI: 1.44-3.52) than the users without it. In multivariate regression, former and current opiate dose and oral use of opiates were independently associated with opioid use disorder. Each ten gram per week increase in opiate dose during the study period almost tripled the odds of opioid use disorder (OR = 3.18; 95%CI: 1.79-5.63).
CONCLUSIONS
Chronic opiate use led to clinical opioid use disorder in more than half of the users, and this disorder was associated with psychological distress, increasing its physical and mental burden in high-risk groups.
Topics: Male; Humans; Middle Aged; Aged; Female; Opiate Alkaloids; Cohort Studies; Prevalence; Opioid-Related Disorders; Risk Factors; Analgesics, Opioid; Opiate Substitution Treatment
PubMed: 38129791
DOI: 10.1186/s12888-023-05436-x -
Emergency Medicine Practice Jun 2024As the United States continues to grapple with the opioid crisis, emergency clinicians are on the front lines of managing patients with opioid use disorder. This issue... (Review)
Review
As the United States continues to grapple with the opioid crisis, emergency clinicians are on the front lines of managing patients with opioid use disorder. This issue reviews tools and best practices in emergency department management of patients with opioid overdose and opioid withdrawal, and how substance use history will inform treatment planning and disposition. As growing evidence shows that medications for opioid use disorder (MOUD)- buprenorphine, methadone, and naltrexone-can have lasting impacts on patients' addiction recovery, strategies for assessing patient readiness for MOUD and overcoming barriers to emergency department initiation of these medications are reviewed. Newer approaches to buprenorphine dosing (high-dose, low-dose, home induction, and long-acting injectable dosing) are also reviewed.
Topics: Humans; Emergency Service, Hospital; Opioid-Related Disorders; Buprenorphine; Opiate Substitution Treatment; Narcotic Antagonists; Methadone; Naltrexone; United States; Analgesics, Opioid
PubMed: 38768011
DOI: No ID Found -
JAMA Jan 2024
Topics: Humans; Administration, Intranasal; Analgesics, Opioid; Drug Overdose; Naloxone; Narcotic Antagonists; Opiate Overdose; Opioid-Related Disorders
PubMed: 38127361
DOI: 10.1001/jama.2023.23248 -
Journal of Pain and Symptom Management Aug 2023Dyspnea is among the most distressing symptoms in the last weeks to days of life (terminal dyspnea). While physicians frequently use parenteral opioids other than...
CONTEXT
Dyspnea is among the most distressing symptoms in the last weeks to days of life (terminal dyspnea). While physicians frequently use parenteral opioids other than morphine for terminal dyspnea, little is known about their effects in cancer patients.
OBJECTIVES
To explore the effectiveness and safety of parenteral morphine, oxycodone, and hydromorphone for cancer patients with terminal dyspnea.
METHODS
This was a secondary analysis of a multicenter cohort study that consecutively enrolled advanced cancer patients with moderate/severe terminal dyspnea. Participating palliative care physicians initiated parenteral opioids (morphine/oxycodone/hydromorphone), utilizing a standardized treatment algorithm. We examined the dyspnea intensity (Integrated Palliative care Outcome Scale [IPOS]) at 24 and 48 hours.
RESULTS
Of 108 patients (mean age = 72), 66 (61%), 34 (32%), and 8 (7.4%) received morphine, oxycodone, and hydromorphone, respectively. At 24 hours, mean dyspnea IPOS scores significantly decreased from 3.0 (standard error (SE) = 0.1) at the baseline to 1.6 (0.1), 2.9 (0.1) to 2.0 (0.2), and 3.5 (0.2) to 1.2 (0.4) in the morphine (P < 0.001), oxycodone (P < 0.001), and hydromorphone (P = 0.011) groups, respectively. At 48 hours, the IPOS scores significantly reduced from 2.9 (0.1) at the baseline to 1.4 (0.1), 2.9 (0.1) to 1.6 (0.2), and 3.5 (0.2) to 1.2 (0.2) in the morphine (P < 0.001), oxycodone (P < 0.001), and hydromorphone (P = 0.004) groups, respectively. No significant differences in mean scores were found among the three groups at 24 (P = 0.080) and 48 hours (P = 0.322). Adverse events were rare.
CONCLUSION
Parenteral morphine, oxycodone, and hydromorphone may be similarly effective and safe for cancer patients with terminal dyspnea.
Topics: Humans; Aged; Analgesics, Opioid; Oxycodone; Hydromorphone; Cohort Studies; Morphine; Dyspnea; Neoplasms
PubMed: 37080479
DOI: 10.1016/j.jpainsymman.2023.04.009 -
Harm Reduction Journal May 2024Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular... (Review)
Review
Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review investigates the adequacy of two doses of standard IM or IN naloxone in reversing fentanyl overdoses compared to newer high-dose naloxone formulations. Moreover, our initiative incorporates the experiences of people who use drugs, enabling a more practical and contextually-grounded analysis. The evidence indicates that the vast majority of fentanyl overdoses can be successfully reversed using two standard IM or IN dosages. Exceptions include cases of carfentanil overdose, which necessitates ≥ 3 doses for reversal. Multiple studies documented the risk of precipitated withdrawal using ≥ 2 doses of naloxone, notably including the possibility of recurring overdose symptoms after resuscitation, contingent upon the half-life of the specific opioid involved. We recommend distributing multiple doses of standard IM or IN naloxone to bystanders and educating individuals on the adequacy of two doses in reversing fentanyl overdoses. Individuals should continue administration until the recipient is revived, ensuring appropriate intervals between each dose along with rescue breaths, and calling emergency medical services if the individual is unresponsive after two doses. We do not recommend high-dose naloxone formulations as a substitute for four doses of IM or IN naloxone due to the higher cost, risk of precipitated withdrawal, and limited evidence compared to standard doses. Future research must take into consideration lived and living experience, scientific evidence, conflicts of interest, and the bodily autonomy of people who use drugs.
Topics: Humans; Naloxone; Narcotic Antagonists; Drug Overdose; Fentanyl; Opiate Overdose; Analgesics, Opioid; Administration, Intranasal
PubMed: 38741224
DOI: 10.1186/s12954-024-00994-z