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JAMA Network Open Jun 2023Prior authorization (PA) requirements for buprenorphine are associated with lower provision of the medication for the treatment of opioid use disorder (OUD). While... (Review)
Review
IMPORTANCE
Prior authorization (PA) requirements for buprenorphine are associated with lower provision of the medication for the treatment of opioid use disorder (OUD). While Medicare plans have eliminated PA requirements for buprenorphine, many Medicaid plans continue to require them.
OBJECTIVE
To describe and classify buprenorphine coverage requirements based on thematic analysis of state Medicaid PA forms.
DESIGN, SETTING, AND PARTICIPANTS
This qualitative study used a thematic analysis of 50 states' Medicaid PA forms for buprenorphine between November 2020 and March 2021. Forms were obtained from the jurisdiction's Medicaid websites and assessed for features suggesting barriers to buprenorphine access. A coding tool was developed based on a review of a sample of forms, including fields for behavioral health treatment recommendations or mandates, drug screening requirements, and dosage limitations.
MAIN OUTCOMES AND MEASURES
Outcomes included PA requirements for different buprenorphine formulations. Additionally, PA forms were evaluated for various criteria such as behavioral health, drug screenings, dose-related recommendations or mandates or patient education.
RESULTS
Among the total of 50 US states in the analysis, most states' Medicaid plans required PA for at least 1 formulation of buprenorphine. However, the majority did not require a PA for buprenorphine-naloxone. Four key themes of coverage requirements were identified: restrictive surveillance (eg, requirements for urine drug screenings, random drug screenings, pill counts), behavioral health treatment recommendations or mandates (eg, mandatory counseling or 12-step meeting attendance), interfering with or restricting medical decision-making (eg, maximum daily dosages of 16 mg, requiring additional steps for dosages higher than 16 mg), and patient education (eg, information about adverse effects and interactions with other medications). Eleven states (22%) required urine drug screenings, 6 states (12%) required random urine drug screenings, and 4 states (8%) required pill counts. Fourteen states' forms (28%) recommended therapy, and 7 (14%) required therapy, counseling, or participation in group sessions. Eighteen states (36%) specified dosage maximums; among them, 11 (22%) required additional steps for a daily dosage higher than 16 mg.
CONCLUSION
In this qualitative study of state Medicaid PA requirements for buprenorphine, themes were identified that included patient surveillance with drug screenings and pill counts, behavioral health treatment recommendations or mandates, patient education, and dosing guidance. These results suggest that state Medicaid plans' buprenorphine PA requirements for OUD are in conflict with existing evidence and may negatively affect states' efforts to address the opioid overdose crisis.
Topics: Aged; Humans; United States; Buprenorphine; Medicaid; Prior Authorization; Medicare; Buprenorphine, Naloxone Drug Combination; Opioid-Related Disorders
PubMed: 37318805
DOI: 10.1001/jamanetworkopen.2023.18487 -
Journal of Psychopharmacology (Oxford,... Sep 2022The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and...
BACKGROUND
The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and consumption have increased. Concern about increasing numbers of alprazolam-related fatalities started circulating in 2018. However, statistics on this issue are very limited. This study examined patterns in such mortality in Scotland.
METHODS
Statistics on deaths where alprazolam was mentioned in the 'cause of death' were obtained from official mortality registers. Anonymised Scottish case-level data were obtained. Data were examined in respect of the characteristics of decedents and deaths using descriptive statistics.
RESULTS
Scotland registered 370 deaths in 2004-2020; 366 of these occurred in 2015-2020: most involved males (77.1%); mean age 39.0 (SD 12.6) years. The principal underlying cause of death was accidental poisoning: opiates/opioids (77.9%); sedatives/hypnotics (15.0%). Two deaths involved alprazolam alone. Main drug groups implicated: opiates/opioids (94.8%), 'other benzodiazepines' (67.2%), gabapentinoids (42.9%), stimulants (30.1%), antidepressants (15.0%). Two-thirds (64.2%) involved combinations of central nervous system (CNS) depressants.
DISCUSSION
Alprazolam-related deaths are likely due to an increasing illicit supply. The fall in deaths in 2019-2020 is partially due to increased use of designer benzodiazepines. Treatment for alprazolam dependence is growing. Clinicians need to be aware of continuing recreational alprazolam use. When such consumption occurs with CNS depressants, overdose and death risks increase.
CONCLUSIONS
More awareness of alprazolam contributing to deaths, especially in conjunction with other CNS depressants, is needed by consumers and clinicians. Improved monitoring of illicit supplies could identify emerging issues of medicines' abuse.
Topics: Adult; Alprazolam; Analgesics, Opioid; Benzodiazepines; Central Nervous System Depressants; Humans; Hypnotics and Sedatives; Male; Opiate Alkaloids; Scotland; State Medicine
PubMed: 35912873
DOI: 10.1177/02698811221104065 -
Journal of the Neurological Sciences Nov 2022Abuse of opiates, cocaine, and lipophilic inhalants (e.g., toluene) can damage brain myelin and cause acute toxic leukoencephalopathy (TL), but little is known about... (Review)
Review
OBJECTIVES
Abuse of opiates, cocaine, and lipophilic inhalants (e.g., toluene) can damage brain myelin and cause acute toxic leukoencephalopathy (TL), but little is known about recovery or prognosis in this condition. In light of the ongoing opiate epidemic in the United States, it is important to understand the natural history of patients who have acute neurological complications from illicit drug exposure. Our aim was to conduct a scoping review of the literature regarding prognosis in described cases of substance abuse-related TL.
METHODS
A strategic search of PubMed, Ovid, Cumulative Index to Nursing, and Allied Health Literature (CINAHL) databases yielded adult cases of acute TL from opiates, cocaine, or inhalants. Cases and case series were eligible for inclusion if they described acute leukoencephalopathy with a clear temporal association with opiate, cocaine, or inhalant abuse. Inclusion was contingent on availability of clinical descriptions until death or ≥ 4 weeks follow-up with neuroimaging consistent with TL.
RESULTS
Among 52 cases from 14 articles, 21 (40.4%) individuals died with mean time to death of 28.2 days; with mean follow-up of 12.8 months, 10 (19.2%) survived with no recovery, 17 (32.7%) had partial recovery, and 4 (7.7%) individuals had full recovery.
CONCLUSION
Substance abuse-related acute TL often has a poor prognosis, but partial or even full recovery is possible in a subgroup of individuals over months to years.
Topics: Adult; Female; Humans; United States; Substance-Related Disorders; Leukoencephalopathies; Illicit Drugs; Cocaine; Toluene; Prognosis; Opiate Alkaloids
PubMed: 36156344
DOI: 10.1016/j.jns.2022.120420 -
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 -
Tijdschrift Voor Psychiatrie 2023Patients with opiate use disorder may be treated medicamentally with methadone and sublingual buprenorphine. However, also two forms of subcutaneous buprenorphine that...
BACKGROUND
Patients with opiate use disorder may be treated medicamentally with methadone and sublingual buprenorphine. However, also two forms of subcutaneous buprenorphine that can be administered weekly or monthly are available.
AIM
To describe the effectiveness and the side effects of the buprenorphine depot.
METHOD
Embase was searched and cross-references were sought in the included studies and previous reviews.
RESULTS
Nine articles were included. One randomized study (n = 428) compared buprenorphine depot to the sublingual form, with the depot being more effective after 12-24 weeks. The other randomized study (n = 504) compared the depot with placebo. The depot was found to be effective. In two comparative non-blinded studies, no significant difference in abstinence was reported between the depot and sublingual administration. Medium-term effectiveness (16-52 weeks) was confirmed in five follow-up studies, in which the depot preparation proved both effective and well tolerated.
CONCLUSION
The buprenorphine depot is described as promising in the international literature. However, there are still several uncertainties that make its prescription should be done with great caution.
Topics: Humans; Buprenorphine; Narcotic Antagonists; Opiate Alkaloids; Opioid-Related Disorders; Methadone
PubMed: 36734687
DOI: No ID Found -
Translational Psychiatry Apr 2023Heroin is an opioid agonist commonly abused for its rewarding effects. Since its synthesis at the end of the nineteenth century, its popularity as a recreational drug... (Review)
Review
Heroin is an opioid agonist commonly abused for its rewarding effects. Since its synthesis at the end of the nineteenth century, its popularity as a recreational drug has ebbed and flowed. In the last three decades, heroin use has increased again, and yet the pharmacology of heroin is still poorly understood. After entering the body, heroin is rapidly deacetylated to 6-monoacetylmorphine (6-MAM), which is then deacetylated to morphine. Thus, drug addiction literature has long settled on the notion that heroin is little more than a pro-drug. In contrast to these former views, we will argue for a more complex interplay among heroin and its active metabolites: 6-MAM, morphine, and morphine-6-glucuronide (M6G). In particular, we propose that the complex temporal pattern of heroin effects results from the sequential, only partially overlapping, actions not only of 6-MAM, morphine, and M6G, but also of heroin per se, which, therefore, should not be seen as a mere brain-delivery system for its active metabolites. We will first review the literature concerning the pharmacokinetics and pharmacodynamics of heroin and its metabolites, then examine their neural and behavioral effects, and finally discuss the possible implications of these data for a better understanding of opioid reward and heroin addiction. By so doing we hope to highlight research topics to be investigated by future clinical and pre-clinical studies.
Topics: Humans; Heroin; Analgesics, Opioid; Morphine Derivatives; Morphine; Heroin Dependence
PubMed: 37031205
DOI: 10.1038/s41398-023-02406-5 -
Journal of General Internal Medicine Dec 2020Despite evidence that medications to treat opioid use disorder (OUD) are effective, most people who could benefit from this treatment do not receive it. This rapid... (Review)
Review
BACKGROUND
Despite evidence that medications to treat opioid use disorder (OUD) are effective, most people who could benefit from this treatment do not receive it. This rapid review synthesizes evidence on current barriers and facilitators to buprenorphine/naloxone and naltrexone at the patient, provider, and system levels to inform future interventions aimed at expanding treatment.
METHODS
We systematically searched numerous bibliographic databases through May 2020 and selected studies published since 2014. Study selection, data abstraction, coding of barriers and facilitators, and quality assessment were first completed by one reviewer and checked by a second.
RESULTS
We included 40 studies of buprenorphine (5 also discussed naltrexone). Four types of patient and provider-level barriers to OUD medication use emerged-stigma related to OUD medications, treatment experiences and beliefs (positive or negative), logistical issues (time and costs as well as insurance and regulatory requirements), and knowledge (high or low) of OUD and the role of medications. Stigma was the most common barrier among patients, while logistical issues were the most common barriers among providers. Facilitators for both patients and providers included peer supports. Most administrator-identified or system-level barriers and facilitators fit into the category of logistical issues. We have moderate confidence in buprenorphine findings but low confidence in naltrexone findings due to the small number of studies.
DISCUSSION
Stigma, treatment experiences, logistical issues, and knowledge gaps are the main barriers associated with low utilization of OUD medications. These barriers can overlap and mutually reinforce each other, but given that, it is plausible that reducing one barrier may lead to reductions in others. The highest priority for future research is to evaluate interventions to reduce stigma. Other priorities for future research include better identification of barriers and facilitators for specific populations, such as those with OUD related to prescription opioids, and for naltrexone use.
PROTOCOL REGISTRATION
PROSPERO; CRD42019133394.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 33145687
DOI: 10.1007/s11606-020-06257-4 -
European Journal of Preventive... Mar 2021Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of...
AIMS
Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.
METHODS AND RESULTS
In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.
CONCLUSION
Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.
Topics: Cardiovascular Diseases; Cohort Studies; Female; Humans; Iran; Male; Mortality; Opiate Alkaloids; Risk Factors
PubMed: 33624066
DOI: 10.1093/eurjpc/zwaa006 -
Identifying and Characterizing Medical Advice-Seekers on a Social Media Forum for Buprenorphine Use.International Journal of Environmental... May 2022Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how...
Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how advice-seekers differ from other users. Our research addresses this gap by identifying key characteristics of r/suboxone users that predict advice-seeking behavior. Objective: The objective of this analysis is to identify and describe advice-seekers on Reddit for buprenorphine-naloxone use using text annotation, social network analysis, and statistical modeling techniques. Methods: We collected 5258 posts and their comments from Reddit between 2014 and 2019. Among 202 posts which met our inclusion criteria, we annotated each post to determine which were advice-seeking (n = 137) or not advice-seeking (n = 65). We also annotated each posting user’s buprenorphine-naloxone use status (current versus formerly taking and, if currently taking, whether inducting or tapering versus other stages) and quantified their connectedness using social network analysis. To analyze the relationship between Reddit users’ advice-seeking and their social connectivity and medication use status, we constructed four models which varied in their inclusion of explanatory variables for social connectedness and buprenorphine use status. Results: The stepwise model containing “total degree” (p = 0.002), “using: inducting/tapering” (p < 0.001), and “using: other” (p = 0.01) outperformed all other models. Reddit users with fewer connections and who are currently using buprenorphine-naloxone are more likely to seek advice than those who are well-connected and no longer using the medication, respectively. Importantly, advice-seeking behavior is most accurately predicted using a combination of network characteristics and medication use status, rather than either factor alone. Conclusions: Our findings provide insights for the clinical care of people recovering from opioid use disorder and the nature of online medical advice-seeking overall. Clinicians should be especially attentive (e.g., through frequent follow-up) to patients who are inducting or tapering buprenorphine-naloxone or signal limited social support.
Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Opioid-Related Disorders; Social Media; Social Networking
PubMed: 35627818
DOI: 10.3390/ijerph19106281 -
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