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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 -
Cancer Epidemiology, Biomarkers &... Mar 2020There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco.
BACKGROUND
There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco.
METHODS
Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers, including tobacco alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC), and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose.
RESULTS
Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users of either product. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene (∑-phe) resulted almost completely from opiate use. Concentrations of most VOC biomarkers were explained by both nicotine dose and opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite and a dimethylformamide metabolite, were more strongly explained by opiate use. Acrylamide metabolites and ∑-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake.
CONCLUSIONS
Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens.
IMPACT
This high exposure, particularly among dual opiate and cigarette users, can have a substantial global public health impact.
Topics: Administration, Oral; Adult; Biomarkers; Carcinogens; Cigarette Smoking; Cohort Studies; Humans; Iran; Male; Middle Aged; Opiate Alkaloids; Smoking, Non-Tobacco Products; Tobacco Products
PubMed: 31915141
DOI: 10.1158/1055-9965.EPI-19-1212 -
Canadian Journal of Psychiatry. Revue... Jul 2017Six recent randomised control trials (RCTs) have suggested that supervised injectable heroin (SIH) can be effective in patients who persist in street heroin use during... (Review)
Review
BACKGROUND
Six recent randomised control trials (RCTs) have suggested that supervised injectable heroin (SIH) can be effective in patients who persist in street heroin use during methadone treatment. However, short-term randomised control trials have limitations in assessing the effectiveness of treatments for addictive disorders, which are chronic and relapsing disorders of motivation. These RCTs particularly fail to capture the process of the SIH treatment and the diversity of influence and change over time.
METHOD
This narrative review is based on the analysis of published data. Conclusions are drawn from a process of reflection informed by experience in delivering one of the published trials, subsequent experiences in varying the way SIH is delivered, and through consideration of possible mechanisms of action of SIH.
OBSERVATIONS
Many long-term, socially marginalised and demoralised people who are addicted to heroin experience few rewards from the stability afforded by methadone treatment. Supervised injected heroin is sufficiently reinforcing for many of these individuals to attend daily and participate in highly structured treatment. With an adequate daily dose of supervised methadone to avoid withdrawal dysphoria, occasional diamorphine injections-not necessarily twice daily, or even every day-is enough to hold people in treatment. Participation was associated with reduced amounts of non-prescribed drug use, a gradual change in self-image and attitude, and for some subjects, a movement towards social reintegration and eventual withdrawal from SIH.
CONCLUSIONS
Prescribed heroin is sufficiently motivating to hold a proportion of recidivist addicts in long-term treatment. Participation in structured treatment provides respite from compulsive drug use, and a proportion of subjects develop sufficient rewards from social reintegration to successfully withdraw from treatment. Such change, when it occurs, is slow and stuttering.
Topics: Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Opiate Substitution Treatment
PubMed: 28683227
DOI: 10.1177/0706743716673966 -
European Journal of Psychotraumatology 2023The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use of opioid antagonists has been proposed as a therapeutic option based on the theory that dissociation might be a phenomenon mediated by dysregulation of the endogenous opioid system.
OBJECTIVE
To review and meta-analyse the available evidence on the efficacy of the opioid antagonists naltrexone, naloxone, and nalmefene as treatments for dissociative symptoms and disorders.
METHOD
The PRISMA guidelines were followed, and this review was registered in Prospero with reference number CRD42021280976. The search was performed in the PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and PubPsych databases.
RESULTS
1,798 citations were obtained. After removing duplicates and applying inclusion and exclusion criteria, we included 5 comparative studies with 9 dissociation measures that had included a total of 154 participants, of whom 134 had been treated with an opioid antagonist. The results of the meta-analysis showed a treatment effect for dissociation when using opioid antagonists [pooled = 1.46 (95% CI: 0.62-2.31)]. However, the studies we included were very heterogeneous [Q = 66.89 ( < .001)] and there may have been publication bias.
CONCLUSIONS
Although more research is needed and the results must be interpreted with caution because of the limited amount of data and heterogeneity in the studies and their methodological qualities, opioid antagonists (particularly naltrexone) are promising candidates for the treatment of dissociative symptoms and showed a moderate - large effect size in reducing these symptoms.
Topics: Humans; Narcotic Antagonists; Naltrexone; Naloxone; Dissociative Disorders
PubMed: 37860852
DOI: 10.1080/20008066.2023.2265184 -
Sleep Sep 2023Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found...
Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.
Topics: Humans; Mice; Animals; Dogs; Orexins; Sodium Oxybate; Cataplexy; Locus Coeruleus; Narcolepsy; Neurons; Opiate Alkaloids
PubMed: 37155728
DOI: 10.1093/sleep/zsad135 -
The Cochrane Database of Systematic... Apr 2014The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless, no studies have been published that systematically assess the effectiveness of the pharmacological detoxification among adolescents.
OBJECTIVES
To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared with no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINHAL (January 1982 to January 2014), Web of Science (1991-January 2014) and reference lists of articles.
SELECTION CRITERIA
Randomised controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13 to 18 years).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by The Cochrane Collaboration
MAIN RESULTS
Two trials involving 190 participants were included. One trial compared buprenorphine with clonidine for detoxification. No difference was found for drop out: risk ratio (RR) 0.45 (95% confidence interval (CI): 0.20 to 1.04) and acceptability of treatment: withdrawal score mean difference (MD): 3.97 (95% CI -1.38 to 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 (95% CI 1.58 to 76.55), quality of evidence moderate.The other trial compared maintenance treatment versus detoxification treatment: buprenorphine-naloxone maintenance versus buprenorphine detoxification. For drop out the results were in favour of maintenance treatment: RR 2.67 (95% CI 1.85, 3.86), as well as for results at follow-up RR 1.36 [95% CI 1.05to 1.76); no differences for use of opiate, quality of evidence low.
AUTHORS' CONCLUSIONS
It is difficult to draw conclusions on the basis of two trials with few participants. Furthermore, the two studies included did not consider the efficacy of methadone that is still the most frequent drug utilised for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people due to practical and ethical reasons.
Topics: Adolescent; Buprenorphine; Clonidine; Humans; Maintenance Chemotherapy; Naloxone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 24777492
DOI: 10.1002/14651858.CD006749.pub3 -
The Cochrane Database of Systematic... Jun 2013The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. People who smoke report positive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. People who smoke report positive effects such as pleasure, arousal, and relaxation as well as relief of negative affect, tension, and anxiety. Opioid (narcotic) antagonists are of particular interest to investigators as potential agents to attenuate the rewarding effects of cigarette smoking.
OBJECTIVES
To evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. The drugs include naloxone and the longer-acting opioid antagonist naltrexone.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register for trials of naloxone, naltrexone and other opioid antagonists and conducted an additional search of MEDLINE using 'Narcotic antagonists' and smoking terms in April 2013. We also contacted investigators, when possible, for information on unpublished studies.
SELECTION CRITERIA
We considered randomised controlled trials comparing opioid antagonists to placebo or an alternative therapeutic control for smoking cessation. We included in the meta-analysis only those trials which reported data on abstinence for a minimum of six months. We also reviewed, for descriptive purposes, results from short-term laboratory-based studies of opioid antagonists designed to evaluate psycho-biological mediating variables associated with nicotine dependence.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate on the study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. Abstinence at end of treatment was a secondary outcome. We extracted cotinine- or carbon monoxide-verified abstinence where available. Where appropriate, we performed meta-analysis, pooling risk ratios using a Mantel-Haenszel fixed-effect model.
MAIN RESULTS
Eight trials of naltrexone met inclusion criteria for meta-analysis of long-term cessation. One trial used a factorial design so five trials compared naltrexone versus placebo and four trials compared naltrexone plus nicotine replacement therapy (NRT) versus placebo plus NRT. Results from 250 participants in one long-term trial remain unpublished. No significant difference was detected between naltrexone and placebo (risk ratio (RR) 1.00; 95% confidence interval (CI) 0.66 to 1.51, 445 participants), or between naltrexone and placebo as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30, 768 participants). The estimate was similar when all eight trials were pooled (RR 0.97; 95% CI 0.76 to 1.24, 1213 participants). In a secondary analysis of abstinence at end of treatment, there was also no evidence of any early treatment effect, (RR 1.03; 95% CI 0.88 to 1.22, 1213 participants). No trials of naloxone or buprenorphine reported abstinence outcomes.
AUTHORS' CONCLUSIONS
Based on data from eight trials and over 1200 individuals, there was no evidence of an effect of naltrexone alone or as an adjunct to NRT on long-term smoking abstinence, with a point estimate strongly suggesting no effect and confidence intervals that make a clinically important effect of treatment unlikely. Although further trials might narrow the confidence intervals they are unlikely to be a good use of resources.
Topics: Buprenorphine; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 23744347
DOI: 10.1002/14651858.CD003086.pub3 -
Molecules (Basel, Switzerland) Feb 2020Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law...
Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law enforcement. A rapid liquid chromatography-tandem mass spectrometry method using "dilute-and-shoot" analysis without the need for extraction, hydrolysis and/or derivatization has been developed and validated. The approach provides linear ranges of 2.5-1000 ng mL for 6-acetylmorphine, codeine, chlorpheniramine, and carbinoxamine, 2.5-800 ng mL for morphine and morphine-3-β-d-glucuronide, and 2.5-600 ng mL for morphine-6-β-d-glucuronide and codeine-6-β-d-glucuronide, with excellent correlation coefficients (R > 0.995) and matrix effects (< 5%). Urine samples collected from the ten participants orally administered cold syrups were analyzed. The results concluded that participants consuming codeine-containing cold syrups did not routinely pass urine tests for opiates, and their morphine-codeine concentration ratios (M/C) were not always < 1. In addition, the distribution map of the clinical total concentration of the sum of morphine and codeine against the antihistamines (chlorpheniramine or carbinoxamine) were plotted for discrimination of people who used cold syrups. The 15 real cases have been studied by using M/C rule, cutoff value, and distribution map, further revealing a potential approach to determine opiate metabolite in urine originating from cold syrups.
Topics: Adult; Analgesics, Opioid; Chlorpheniramine; Codeine; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Histamine Antagonists; Humans; Male; Middle Aged; Morphine; Morphine Derivatives; Opiate Alkaloids; Pyridines; Young Adult
PubMed: 32098143
DOI: 10.3390/molecules25040972 -
JAMA Network Open Oct 2023Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies...
IMPORTANCE
Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies examining associations between OM and clinical outcomes were performed in the era of 3-dimensional conformal RT planning with low rates of concurrent chemotherapy, and thus may not reflect current practice.
OBJECTIVE
To prospectively assess patient-reported OM and identify its associations with clinical outcomes and quality of life.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study performed at a single institution included 702 consecutive patients who underwent definitive or adjuvant intensity-modulated RT (IMRT) for primary HNC from February 9, 2015, to May 27, 2022. Data were analyzed from November 28, 2022, to August 18, 2023.
MAIN OUTCOMES AND MEASURES
Severity of OM was assessed based on highest reported mouth and throat soreness (MTS) score during radiotherapy according to the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer survey, which was administered weekly during IMRT. Linear mixed models were used to compare mean MTS scores grouped by disease site and chemotherapy regimen. Fisher exact tests and 1-way analysis of variance tests were performed to identify associations between severity of OM and clinical outcomes.
RESULTS
Among 576 eligible patients, the median age was 62.5 (IQR, 56.3-69.1) years, and 451 patients (78.3%) were men. In terms of race and ethnicity, 6 patients (1.0%) were American Indian or Alaska Native; 2 (0.3%), Asian; 31 (5.4%), Black; 8 (1.4%), Hispanic or Latino; 509 (88.4%), White; and 28 (4.9%), unknown. The most common treatment site was oropharynx (268 [46.5%]), and most patients received concurrent chemotherapy (464 [80.6%]). By the end of treatment, 360 patients (62.5%) developed severe OM and 568 (98.6%) developed some degree of OM. Linear mixed models found no significant differences in OM between HNC disease sites. Groups with greater highest severity of OM reported had higher rates of measured outcomes (listed respectively by MTS score 0, 1, 2, 3, and 4): feeding tube placement (0%, 3.6% [2 of 56], 6.6% [10 of 152], 14.7% [40 of 272], and 21.6% [19 of 88]; P = .001), hospitalization (12.5% [1 of 8], 10.7% [6 of 56], 15.1% [23 of 152], 23.9% [65 of 272], and 28.4% [25 of 88]; P = .02), opiate use (0%, 19.6% [11 of 56], 42.8%[65 of 152], 61.4% [167 of 272], and 64.8% [57 of 88]; P < .001) and experienced greater weight loss (median, -0.7 [IQR, -1.7 to -0.4] kg; median, 3.9 [IQR, 1.1 to 6.1] kg; median, 5.0 [IQR, 2.2 to 7.7] kg; median, 4.7 [IQR, 2.1 to 7.7] kg; and median, 7.7 [IQR, 2.8 to 10.6] kg; P < .001).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with HNC, 62.5% developed severe OM. Higher severity of OM was associated with feeding tube placement, hospitalization, opiate use, and weight loss. Improvements in OM prevention and management are needed.
Topics: Male; Humans; Middle Aged; Female; Radiotherapy, Intensity-Modulated; Cohort Studies; Quality of Life; Head and Neck Neoplasms; Stomatitis; Opiate Alkaloids; Weight Loss
PubMed: 37819659
DOI: 10.1001/jamanetworkopen.2023.37265 -
International Journal of Legal Medicine Jul 2023The most common pulmonary findings in opiate-related fatalities are congestion and oedema, as well as acute and/or chronic alveolar haemorrhage, the cause of which is...
The most common pulmonary findings in opiate-related fatalities are congestion and oedema, as well as acute and/or chronic alveolar haemorrhage, the cause of which is thought to be a damage to the capillary endothelium related to ischemia. Human vascular mesenchymal stromal cells (vMSCs) play a fundamental role in tissue regeneration and repair after endothelial cell injury, and they express opioid receptors. The aim of this study was to assess the effect of in vitro morphine exposure on the physiological activity and maintenance of human vMSCs. vMSCs were obtained from abdominal aorta fragments collected during surgery repair and were exposed to incremental doses (0.1 mM, 0.4 mM, 0.8 mM and 1 mM) of morphine sulphate for 7 days. The effect was investigated through cell viability assessment, proliferation assay, reactive oxygen species (ROS) detection assay, senescence-associated β-galactosidase assay, senescent-related markers (p21 and p16) and the apoptosis-related marker caspase 3. Moreover, an ultrastructural analysis by transmission electron microscopy and in vitro vascular differentiation were evaluated. Results showed a decrease of the cellular metabolic activity, a pro-oxidant and pro-senescence effect, an increase in intracellular ROS and the activation of the apoptosis signalling, as well as ultrastructural modifications and impairment of vascular differentiation after morphine treatment of vMSC. Although confirmation studies are required on real fatal opiate intoxications, the approach based on morphological and immunofluorescence methodologies may have a high potential also as a useful tool or as a complementary method in forensic pathology. The application of these techniques in the future may lead to the identification of new markers and morphological parameters useful as complementary investigations for drug-related deaths.
Topics: Humans; Cellular Senescence; Reactive Oxygen Species; Opiate Alkaloids; Mesenchymal Stem Cells; Morphine Derivatives
PubMed: 36786894
DOI: 10.1007/s00414-023-02961-y