Availability of Long-Acting Injectable Buprenorphine at Substance Use Treatment Facilities in 2021.

This study assesses the proportion of US substance use and mental health care facilities that offered any medications for opioid use disorder and, specifically, long-acting injectable buprenorphine in 2021.

Intranasal Naloxone for Opioid Overdose.

This JAMA Insights describes indications for naloxone use in preventing opioid overdoses and benefits vs barriers to its availability following FDA approval of its availability without a prescription.

Racial Inequality in Receipt of Medications for Opioid Use Disorder.

BACKGROUND: Since 2010, Black persons in the United States have had a greater increase in opioid overdose-related mortality than other groups, but national-level evidence characterizing racial and ethnic disparities in the use of medications for opioid use disorder (OUD) is limited. METHODS: We used Medicare claims data from the 2016-2019 period for a random 40% sample of fee-for-service beneficiaries who were Black, Hispanic, or White; were eligible for Medicare owing to disability; and had an index event related to OUD (nonfatal overdose treated in an emergency department or inpatient setting, hospitalization with injection drug use-related infection, or inpatient or residential rehabilitation or detoxification care). We measured the receipt of medications to treat OUD (buprenorphine, naltrexone, and naloxone), the receipt of high-risk medications (opioid analgesics and benzodiazepines), and health care utilization, all in the 180 days after the index event. We estimated differences in outcomes according to race and ethnic group with adjustment for beneficiary age, sex, index event, count of chronic coexisting conditions, and state of residence. RESULTS: We identified 25,904 OUD-related index events among 23,370 beneficiaries, with 3937 events (15.2%) occurring among Black patients, 2105 (8.1%) among Hispanic patients, and 19,862 (76.7%) among White patients. In the 180 days after the index event, patients received buprenorphine after 12.7% of events among Black patients, after 18.7% of those among Hispanic patients, and after 23.3% of those among White patients; patients received naloxone after 14.4%, 20.7%, and 22.9%, respectively; and patients received benzodiazepines after 23.4%, 29.6%, and 37.1%, respectively. Racial differences in the receipt of medications to treat OUD did not change appreciably from 2016 to 2019 (buprenorphine receipt: after 9.1% of index events among Black patients vs. 21.6% of those among White patients in 2016, and after 14.1% vs. 25.5% in 2019). In all study groups, patients had multiple ambulatory visits in the 180 days after the index event (mean number of visits, 6.6 after events among Black patients, 6.7 after events among Hispanic patients, and 7.6 after events among White patients). CONCLUSIONS: Racial and ethnic differences in the receipt of medications to treat OUD after an index event related to this disorder among patients with disability were substantial and did not change over time. The high incidence of ambulatory visits in all groups showed that disparities persisted despite frequent health care contact. (Funded by the National Institute on Drug Abuse and the National Institute on Aging.).

Association Between Sublingual Buprenorphine-Naloxone Exposure and Dental Disease.

This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database.

Nonfatal opioid overdoses before and after Covid-19: Regional variation in rates of change.

BACKGROUND: The Covid-19 pandemic and its accompanying public-health orders (PHOs) have led to (potentially countervailing) changes in various risk factors for overdose. To assess whether the net effects of these factors varied geographically, we examined regional variation in the impact of the PHOs on counts of nonfatal overdoses, which have received less attention than fatal overdoses, despite their public health significance. METHODS: Data were collected from the Overdose Detection Mapping Application Program (ODMAP), which recorded suspected overdoses between July 1, 2018 and October 25, 2020. We used segmented regression models to assess the impact of PHOs on nonfatal-overdose trends in Washington DC and the five geographical regions of Maryland, using a historical control time series to adjust for normative changes in overdoses that occurred around mid-March (when the PHOs were issued). RESULTS: The mean level change in nonfatal opioid overdoses immediately after mid-March was not reliably different in the Covid-19 year versus the preceding control time series for any region. However, the rate of increase in nonfatal overdose was steeper after mid-March in the Covid-19 year versus the preceding year for Maryland as a whole (B = 2.36; 95% CI, 0.65 to 4.06; p = .007) and for certain subregions. No differences were observed for Washington DC. CONCLUSIONS: The pandemic and its accompanying PHOs were associated with steeper increases in nonfatal opioid overdoses in most but not all of the regions we assessed, with a net effect that was deleterious for the Maryland region as a whole.

Association Between Increased Dispensing of Opioid Agonist Therapy Take-Home Doses and Opioid Overdose and Treatment Interruption and Discontinuation.

Importance: During the COVID-19 pandemic, modified guidance for opioid agonist therapy (OAT) allowed prescribers to increase the number of take-home doses to promote treatment retention. Whether this was associated with an increased risk of overdose is unclear. Objective: To evaluate whether increased take-home doses of OAT early in the COVID-19 pandemic was associated with treatment retention and opioid-related harm. Design, Setting, and Participants: A retrospective propensity-weighted cohort study of 21 297 people actively receiving OAT on March 21, 2020, in Ontario, Canada. Changes in OAT take-home dose frequency were assessed between March 22, 2020, and April 21, 2020, and individuals were observed for up to 180 days to assess outcomes (last date of follow-up, October 18, 2020). Exposures: Exposure was defined as extended take-home doses in the first month of the pandemic within each of 4 cohorts based on OAT type and baseline take-home dose frequency (daily dispensed methadone, 5-6 take-home doses of methadone, daily dispensed buprenorphine/naloxone, and 5-6 take-home doses of buprenorphine/naloxone). Main Outcomes and Measures: Primary outcomes were opioid overdose, interruption in OAT, and OAT discontinuation. Results: Among 16 862 methadone and 4435 buprenorphine/naloxone recipients, the median age ranged between 38 and 42 years, and 29.1% to 38.2% were women. Among individuals receiving daily dispensed methadone (n = 5852), initiation of take-home doses was significantly associated with lower risks of opioid overdose (6.9% vs 9.5%/person-year; weighted hazard ratio [HR], 0.73 [95% CI, 0.56-0.96]), treatment discontinuation (51.0% vs 63.6%/person-year; weighted HR, 0.80 [95% CI, 0.72-0.90]), and treatment interruption (19.0% vs 23.9%/person-year; weighted HR, 0.80 [95% CI, 0.67-0.95]) compared with no change in take-home doses. Among individuals receiving daily dispensed buprenorphine/naloxone (n = 662), there was no significant difference in any outcomes between exposure groups. Among individuals receiving weekly dispensed OAT (n = 11 010 for methadone; n = 3773 for buprenorphine/naloxone), extended take-home methadone doses were significantly associated with lower risks of OAT discontinuation (14.1% vs 19.6%/person-year; weighted HR, 0.72 [95% CI, 0.62-0.84]) and interruption in therapy (5.1% vs 7.4%/person-year; weighted HR, 0.69 [95% CI, 0.53-0.90]), and extended take-home doses of buprenorphine/naloxone were significantly associated with lower risk of interruption in therapy (9.5% vs 12.9%/person-year; weighted HR, 0.74 [95% CI, 0.56-0.99]) compared with no change in take-home doses. Other primary outcomes were not significantly different between groups. Conclusions and Relevance: In Ontario, Canada, during the COVID-19 pandemic, dispensing of increased take-home doses of opioid agonist therapy was significantly associated with lower rates of treatment interruption and discontinuation among some subsets of patients receiving opioid agonist therapy, and there were no statistically significant increases in opioid-related overdoses over 6 months of follow-up. These findings may be susceptible to residual confounding and should be interpreted cautiously.

New Naloxone Concentration Treats Opioid Overdose.

The Food and Drug Administration has approved another injectable form of naloxone in the effort to control opioid deaths. Zimhi is a single-dose prefilled syringe containing 5 mg/0.5 mL of naloxone. Zimhi is administered subcutaneously or intramuscularly.Nurses should educate patients receiving opioids and their families on how to use Zimhi or other prescribed naloxone products.

The role of managed care pharmacy in coprescribing naloxone for patients with specific risk: recommendations from the AMCP Addiction Advisory Group.

Prescription opioid misuse remains a significant cause of morbidity and mortality associated with drug overdose. Researchers, government agencies, public health interests, and professional organizations support the benefits of naloxone coprescribing for patients on chronic opioid therapy to prevent deaths from opioid overdose. However, gaps remain in the provision of naloxone to patients at risk. Currently, less than 1% of patients who should be prescribed naloxone with their opioid medications obtain a prescription for naloxone, illustrating an opportunity for health care providers to conduct thorough risk assessments for patients taking opioids and coprescribing naloxone to those at risk. There are documented barriers to the provision of naloxone for primary care providers, pharmacists, and patients. Managed care organizations have also created barriers. To better understand and evaluate trends in treatment, coverage, policies, and needs associated with providing health services to patients with substance use disorders, the Academy of Managed Care Pharmacy (AMCP) Addiction Advisory Group conducted a survey in 2019. Eighty percent of the managed behavioral health organizations and 47% of AMCP payer members who responded to the survey encouraged naloxone coprescribing in patients at high risk of overdose; however, no organizations require coprescribing. Health plans, managed care organizations, prescribers, pharmacists, patients, and others have important roles in decreasing the morbidity and mortality associated with opioid overdose. In particular, managed care organizations can take specific and meaningful actions to implement payment policies that improve naloxone coprescribing for patients at risk. In this article, opportunities have been outlined for managed care leadership that actively support public health policies for naloxone coprescribing, and 7 recommendations are presented. DISCLOSURES: The AMCP Addiction Advisory Group and the development of this article were supported by Alkermes and Precision Toxicology. Sponsors participated in the advisory group, which provided guidance in the development of the manuscript. Dharbhamalla is employed by AMCP. Skelton is a paid consultant working with AMCP.

Self-harm and suicide during and after opioid agonist treatment among primary care patients in England: a cohort study.

BACKGROUND: The first 4 weeks after initiation and cessation of opioid agonist treatment for opioid dependence are associated with an increased risk of all-cause mortality and overdose. We aimed to investigate whether the rate of self-harm and suicide among people who were prescribed opioid agonist treatment differs during initiation, cessation, and the remainder of time on and off treatment. METHODS: We did a retrospective cohort study and used health-care records from UK Clinical Practice Research Datalink, linked to mortality and hospital admission data, for adults (age 18-75 years at cohort entry) who were prescribed opioid agonist treatment at least once in primary care in England between Jan 2, 1998, and Nov 30, 2018. We estimated rates and adjusted risk ratios (aRRs) of hospital admissions for self-harm and death by suicide, comparing time during and after treatment, as well as comparing stable periods of time on treatment with treatment initiation, cessation, and the remaining time off treatment. FINDINGS: Between Jan 2, 1998, and Nov 30, 2018, 8070 patients (5594 [69·3%] men and 2476 [30·7%] women) received 17 004 episodes of opioid agonist treatment over 40 599 person-years. Patients were mostly of White ethnicity (7006 [86·8%] patients). 807 episodes of self-harm (1·99 per 100 person-years) and 46 suicides (0·11 per 100 person-years) occurred during the study period. The overall age-standardised and sex-standardised mortality ratio for suicide was 7·5 times (95% CI 5·5-10·0) higher in the study cohort than in the general population. Opioid agonist treatment was associated with a reduced risk of self-harm (aRR in periods off treatment 1·50 [95% CI 1·21-1·88]), but was not significantly associated with suicide risk (aRR in periods off treatment 1·21 [0·64-2·28]). Risk of self-harm (aRR 2·60 [95% CI 1·83-3·70]) and suicide (4·68 [1·63-13·42]) were both elevated in the first 4 weeks after stopping opioid agonist treatment compared with stable periods on treatment. INTERPRETATION: Stable periods of opioid agonist treatment are associated with reduced risk of self-harm, emphasising the importance of improving retention of patients in treatment. The first month following cessation of opioid agonist treatment is a period of increased risk of suicide and self-harm, during which additional psychosocial support is required. FUNDING: Medical Research Council.

Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis.

BACKGROUND: Recent studies suggest that lipids, including free fatty acids (FFAs), are necessary for proper µ opioid receptor (MOR) binding and that activation of opioid receptors (ORs) improves intestinal inflammation. The objective of the study was to investigate a possible interaction between the ORs and FFA receptors (FFARs) ligands in the colitis. METHODS: The potential synergistic effect of ORs and FFARs ligands was evaluated using mouse model of acute colitis induced by dextran sulfate sodium (DSS, 4%). Compounds were injected intraperitoneally (i.p.) once or twice daily at the doses of 0.01 or 0.02 mg/kg body weight (BW) (DAMGO-an MOR agonist), 0.3 mg/kg BW (DPDPE-a δ OR (DOR) agonist) and 1 mg/kg BW (naloxone-a non-selective OR antagonist, GLPG 0974-a FFAR2 antagonist, GSK 137647-a FFAR4 agonist and AH 7614-a FFAR4 antagonist) for 4 days. RESULTS: Myeloperoxidase (MPO) activity was significantly decreased after DAMGO (0.02 mg/kg BW) and GSK 137647 (1 mg/kg BW) administration and co-administration as compared to DSS group. CONCLUSIONS: Treatment with ligands of ORs and FFARs may affect the immune cells in the inflammation; however, no significant influence on the severity of colitis and no synergistic effect were observed.

Accuracy in recognising happy facial expressions is associated with antidepressant response to a NOP receptor antagonist but not placebo treatment.

BACKGROUND: Clinical trials with putative antidepressants can be difficult to execute as it can take up to 8 weeks before differences emerge between drug and placebo, and long expensive trials often fail. Implementation of early response biomarkers could aid this process significantly with potential to identify new treatments. AIMS: In a secondary analysis, we examined the association of early effects on emotional processing with later clinical outcome following treatment with the novel NOP antagonist LY2940094 versus placebo. We hypothesised that early induction of positive bias would be associated with reduced severity of depression after 8 weeks of treatment. METHODS: This was a multicentre, randomised, double-blind, parallel-group, fixed-dose, placebo-controlled, 8 week study to assess sensitivity of the facial emotional recognition task (FERT) to early changes in emotional bias induced by LY2940094. Patients who met diagnostic criteria for major depression were randomised to receive LY2940094 (N = 70) or placebo (N = 66). At week 1 and 6, the FERT was completed by 33 patients in the LY2940094 group and 34 in the placebo group. RESULTS: Patients identified happy faces with higher accuracy (Wald χ2(1,33) = 14.25, p < 0.001) after 1 week treatment with LY290094 compared to placebo (Wald χ2(1,32) = 0.83, p = 0.36) and this correlated with eventual treatment response measured by the Hamilton Depression Rating Scale 7 weeks later. CONCLUSION: These data suggest that emotional processing biomarkers may be sensitive to early effects of antidepressant treatment indicative of later clinical response. Further studies in this area may be useful in developing new treatments and clinical trial designs for predicting antidepressant response.

[Overdose from a patch]. / Überdosis durch ein Pflaster.

HISTORY AND CLINICAL FINDINGS: We present the case of an 89-year-old patient with impaired consciousness for whom the emergency services were called. She was soporose and showed a pronounced generalized muscle rigidity. Due to a third-party history the incorrect use of a fentanyl patch was found out to be at cause. TREATMENT AND CLINICAL COURSE: The antidote administration of naloxone led to restoration. The need for repetitive administration confirmed the clinical hypothesis. CONCLUSION: The application of fentanyl via the skin in the form of transdermal therapeutic systems (TTS) has become more popular over the years. Incorrect administration causes intoxication with the leading symptoms of loss of consciousness and respiratory depression. This case report extends the spectrum of symptoms to include skeletal muscle rigidity otherwise only described in connection with intravenous administration, especially in anaesthetic settings.