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Addiction (Abingdon, England) Oct 2023The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the...
AIMS
The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the same drug) during 10 years for more than 200 psychoactive prescription drugs in the 67 million inhabitants in France.
DESIGN
This was a nation-wide, repeated cross-sectional study.
SETTING AND PARTICIPANTS
Data are from the French National Health Data System in 2010, 2015 and 2019 for 214 psychoactive prescription drugs (i.e. anaesthetics, analgesics, antiepileptics, anti-Parkinson drugs, psycholeptics, psychoanaleptics, other nervous system drugs and antihistamines for systemic use).
MEASUREMENTS
The detection and quantification of doctor-shopping relied upon an algorithm that detects overlapping prescriptions from repeated visits to different physicians. We used two doctor-shopping indicators aggregated at population level for each drug dispensed to more than 5000 patients: (i) the quantity doctor-shopped, expressed in defined daily doses (DDD), which measures the total quantity doctor-shopped by the study population for a given drug; and (ii) the proportion doctor-shopped, expressed as a percentage, which standardizes the quantity doctor-shopped according to the use level of the drug.
FINDINGS
The analyses included approximately 200 million dispensings to approximately 30 million patients each year. Opioids (e.g. buprenorphine, methadone, morphine, oxycodone and fentanyl), benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) (e.g. diazepam, oxazepam, zolpidem and clonazepam) had the highest proportions doctor-shopped during the study period. In most cases, the proportion and the quantity doctor-shopped increased for opioids and decreased for benzodiazepines and Z-drugs. Pregabalin had the sharpest increase in the proportion doctor-shopped (from 0.28 to 1.40%), in parallel with a sharp increase in the quantity doctor-shopped (+843%, from 0.7 to 6.6 DDD/100 000 inhabitants/day). Oxycodone had the sharpest increase in the quantity doctor-shopped (+1000%, from 0.1 to 1.1 DDD/100 000 inhabitants/day), in parallel with a sharp increase in the proportion doctor-shopped (from 0.71 to 1.41%). Detailed results for all drugs during the study period can be explored interactively at: https://soeiro.gitlab.io/megadose/.
CONCLUSIONS
In France, doctor-shopping occurs for many drugs from many pharmacological classes, and mainly involves opioid maintenance drugs, some opioids analgesics, some benzodiazepines and Z-drugs and pregabalin.
Topics: Prescription Drug Misuse; Prescription Drugs; Cross-Sectional Studies; Psychotropic Drugs; France; Humans; Office Visits
PubMed: 37203878
DOI: 10.1111/add.16261 -
The Primary Care Companion For CNS... Nov 2023Opioid misuse/abuse is a pervasive problem in the United States, and the growing use of fentanyl-contaminated products is adding fuel to the opioid crisis. To review... (Review)
Review
Opioid misuse/abuse is a pervasive problem in the United States, and the growing use of fentanyl-contaminated products is adding fuel to the opioid crisis. To review the rising prevalence of nonprescription fentanyl in counterfeit oxycodone, paying specific attention to oxycodone for cost analysis. A literature search was performed using 3 databases (Google Scholar, PubMed, and Clinical Key) to identify English-language articles published from January 2010 to October 2022. Search terms were and . An additional search of was performed to gather more information about the pharmacology behind fentanyl overdoses. Studies and articles were selected based on information related to the presence of non-prescription fentanyl in illicit supplies of oxycodone. Additional articles were included to demonstrate the cost, manufacturing, and overdose rates of fentanyl-laced counterfeit opioids. A total of 13 articles were included in the final review. The demand for illicit oxycodone provides an opportunity in which counterfeiters can thrive, using dangerous adulterating agents such as fentanyl to maximize their profits. Those purchasing oxycodone illicitly may or may not be aware of the presence of fentanyl in their tablets, which has clearly resulted in rising overdose numbers. Clinicians should counsel patients at risk for opioid misuse on the risks of counterfeit oxycodone. .
Topics: Humans; Analgesics, Opioid; Drug Overdose; Fentanyl; Opiate Overdose; Opioid-Related Disorders; Oxycodone; United States
PubMed: 37976226
DOI: 10.4088/PCC.22nr03433 -
BioRxiv : the Preprint Server For... Dec 2023Oxycodone is commonly prescribed for moderate to severe pain disorders. While efficacious, long-term use can result in tolerance, physical dependence, and the...
Oxycodone is commonly prescribed for moderate to severe pain disorders. While efficacious, long-term use can result in tolerance, physical dependence, and the development of opioid use disorder. Cannabis and its derivatives such as Δ-Tetrahydrocannabinol (Δ-THC) have been reported to enhance oxycodone analgesia in animal models and in humans. However, it remains unclear if Δ-THC may facilitate unwanted aspects of oxycodone intake, such as tolerance, dependence, and reward at analgesic doses. This study sought to evaluate the impact of co-administration of Δ-THC and oxycodone across behavioral measures related to antinociception, dependence, circadian activity, and reward in both male and female mice. Oxycodone and Δ-THC produced dose-dependent antinociceptive effects in the hotplate assay that were similar between sexes. Repeated treatment (twice daily for 5 days) resulted in antinociceptive tolerance. Combination treatment of oxycodone and Δ-THC produced a greater antinociceptive effect than either administered alone, and delayed the development of antinociceptive tolerance. Repeated treatment with oxycodone produced physical dependence and alterations in circadian activity, neither of which were exacerbated by co-treatment with Δ-THC. Combination treatment of oxycodone and Δ-THC produced CPP when co-administered at doses that did not produce preference when administered alone. These data indicate that Δ-THC may facilitate oxycodone-induced antinociception without augmenting certain unwanted features of opioid intake (e.g. dependence, circadian rhythm alterations). However, our findings also indicate that Δ-THC may facilitate rewarding properties of oxycodone at therapeutically relevant doses which warrant consideration when evaluating this combination for its potential therapeutic utility.
PubMed: 38105953
DOI: 10.1101/2023.12.04.569809 -
Drug Safety Nov 2023Opioids are commonly used as analgesics; however, like any medicine, they can produce adverse drug reactions (ADRs), including nausea, constipation, dependence, and...
INTRODUCTION
Opioids are commonly used as analgesics; however, like any medicine, they can produce adverse drug reactions (ADRs), including nausea, constipation, dependence, and respiratory depression, that result in harmful and fatal events. Therefore, it is essential to monitor the safety of these drugs in clinical practice.
OBJECTIVE
This study aimed to characterize the safety profile of opioids by conducting a descriptive study based on a spontaneous reporting system (SRS) for ADRs in The Netherlands, focusing on abuse, misuse, medication errors, and differences between sexes.
METHODS
Reports submitted to the Netherlands Pharmacovigilance Centre Lareb from January 2003 to December 2021 with an opioid drug as the suspected/interacting medicine were analyzed. Reporting odds ratios (RORs) for drug-ADR combinations were calculated, analyzed, and corrected for sex and drug utilization (expenditure) for the Dutch population.
RESULTS
A total of 8769 reports were analyzed. Tramadol was the opioid with the most reports during the period (n = 2746), while oxycodone or tramadol had the highest number of reports per year in the study period. The most reported ADRs from opioid use were nausea, followed by dizziness and vomiting, independent of sex, and all of them were more often reported in women. Vomiting associated with tramadol (ROR females/males = 2.17) was significantly higher in women. Buprenorphine was responsible for most ADRs when corrected for expenditure, with high RORs observed with application site hypersensitivity, application site reaction, and application site rash. Fentanyl gave rise to most of the reports of ADRs concerning abuse, misuse, and medication errors.
CONCLUSION
Patients treated with opioids experienced ADRs, primarily nausea, dizziness, and vomiting. For those groups of drugs, no significant differences were found between the sexes, except for the vomiting associated with tramadol. In general, ADRs related to opioids presented higher RORs when uncorrected and corrected for sexes and expenditure than other drugs. There was more disproportionate reporting for ADRs concerning abuse, misuse, and medication errors for opioids than other drugs in the Dutch SRS.
Topics: Male; Humans; Female; Analgesics, Opioid; Tramadol; Pharmacovigilance; Dizziness; Drug-Related Side Effects and Adverse Reactions; Vomiting; Nausea; Adverse Drug Reaction Reporting Systems
PubMed: 37824028
DOI: 10.1007/s40264-023-01351-y -
Behavioural Pharmacology Jun 2024Excessive prescribing and misuse of prescription opioids, such as oxycodone, significantly contributed to the current opioid crisis. Although oxycodone is typically...
Excessive prescribing and misuse of prescription opioids, such as oxycodone, significantly contributed to the current opioid crisis. Although oxycodone is typically consumed orally by humans, parenteral routes of administration have primarily been used in preclinical models of oxycodone dependence. To address this issue, more recent studies have used oral self-administration procedures to study oxycodone seeking and withdrawal in rodents. Behavioral differences, however, following oral oxycodone intake versus parenteral oxycodone administration remain unclear. Thus, the goal of the current studies was to compare anxiety- and withdrawal-like behaviors using established opioid dependence models of either home cage oral intake of oxycodone (0.5 mg/ml) or repeated subcutaneous (s.c.) injections of oxycodone (10 mg/kg) in male and female mice. Here, mice received 10 days of oral or s.c. oxycodone administration, and following 72 h of forced abstinence, anxiety- and withdrawal-like behaviors were measured using elevated zero maze, open field, and naloxone-induced precipitated withdrawal procedures. Global withdrawal scores were increased to a similar degree following oral and s.c. oxycodone use, while both routes of oxycodone administration had minimal effects on anxiety-like behaviors. When examining individual withdrawal-like behaviors, mice receiving s.c. oxycodone exhibited more paw tremors and jumps during naloxone-induced precipitated withdrawal compared with oral oxycodone mice. These results indicate that both models of oxycodone administration are sufficient to elevate global withdrawal scores, but, when compared with oral consumption, s.c. oxycodone injections yielded more pronounced effects on some withdrawal-like behaviors.
PubMed: 38847447
DOI: 10.1097/FBP.0000000000000780 -
BMC Geriatrics Apr 2024Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex...
BACKGROUND
Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA.
METHODS
This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models.
RESULTS
The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons.
CONCLUSIONS
Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.
Topics: Humans; Aged; United States; Analgesics, Opioid; Tramadol; Oxycodone; Arthroplasty, Replacement, Knee; Hydrocodone; Retrospective Studies; Arthroplasty, Replacement, Hip; Medicare
PubMed: 38580920
DOI: 10.1186/s12877-024-04933-2 -
World Journal of Emergency Medicine 2024To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments (EDs) in the USA from...
BACKGROUND
To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments (EDs) in the USA from 2007 to 2018.
METHODS
Data were gathered from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2007 to 2018. The study population included individuals of all ages presenting to USA EDs. The NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back pain. The main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time period.
RESULTS
There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007 (244,000 visits) to 2018 (92,000 visits). The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older (from 43.8% to 57.6%), female patients (from 54.5% to 62.0%), black patients (from 22.5% to 30.4%), and Hispanic/Latino patients (from 9.4% to 19.6%). Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007, with a decrease to 68.5% in 2018. Pure oxycodone was the second most prescribed medication, accounting for 6.1% in 2007 and 31.5% in 2018.
CONCLUSION
The overall number of oxycodone-containing analgesics decreased significantly from 2007 to 2018. However, that number trended upward in 45-year-old and older, female, black, or Hispanic/Latino patients from 2007 to 2018. The total amount of pure oxycodone increased significantly from 2007 to 2008.
PubMed: 38855375
DOI: 10.5847/wjem.j.1920-8642.2024.002 -
Scientific Reports Nov 2023Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of...
Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with homecage access to alcohol (20% v/v) and/or water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent a cue-primed reinstatement test and brains were processed for c-fos mRNA expression. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, only female oxycodone + alcohol rats exhibited decreased demand elasticity and increased cue-primed reinstatement. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor expressing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.
Topics: Female; Rats; Male; Animals; Oxycodone; Motivation; Sucrose; Alcohol Drinking; Ethanol; Receptors, Dopamine; Neurons; Water; Self Administration; Extinction, Psychological
PubMed: 37932476
DOI: 10.1038/s41598-023-46111-1 -
Oncology Letters Aug 2023There have been few studies on predictive biomarkers that may be useful to select the most suitable opioids to optimize therapeutic efficacy in individual patients with...
There have been few studies on predictive biomarkers that may be useful to select the most suitable opioids to optimize therapeutic efficacy in individual patients with cancer pain. We recently investigated the efficacy of morphine and oxycodone using single nucleotide polymorphisms (SNPs) of the catechol-O-methyltransferase () rs4680 gene as a biomarker (RELIEF study). To explore additional biomarkers that may enable the selection of an appropriate opioid for individual patients with cancer pain, three SNPs were examined: C-C motif chemokine ligand 11 (; rs17809012), histamine N-methyltransferase (; rs1050891) and transient receptor potential V1 (; rs222749), which were screened from 74 pain-related SNPs. These SNPs, which were identified as being significantly associated with the analgesic effect of morphine, were then used to genotype the 135 patients in the RELIEF study who had been randomized into a morphine group (n=69) or an oxycodone group (n=66). The present study then assessed whether the SNPs could also be used as selective biomarkers to predict which opioid(s) might be the most suitable to provide pain relief for patients with cancer. Oxycodone tended to provide superior analgesic effects over morphine in patients carrying the genotype AA for the rs17809012 SNP (P=0.012 for interaction), suggesting that it could serve as a potential biomarker for personalized analgesic therapy for patients suffering with cancer pain.
PubMed: 37545623
DOI: 10.3892/ol.2023.13941 -
BioRxiv : the Preprint Server For... Jul 2023Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol would influence intake of...
Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol would influence intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with access to either alcohol (20% v/v) and water or only water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent extinction training and brains were processed for c-fos mRNA expression immediately following a cue-primed reinstatement test. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, female oxycodone+alcohol rats exhibited decreased demand elasticity for intravenous oxycodone and increased cue-primed reinstatement while male rats did not. Spontaneous withdrawal signs were correlated with oxycodone intake while alcohol intake was correlated with anxiety-like behavior. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor containing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and alters the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.
PubMed: 37546763
DOI: 10.1101/2023.07.20.549769