Benzodiazepine use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study 🔓

BMC Medicine

This study examined the relationship between benzodiazepine (BZD) use and dementia, using data from the population-based Rotterdam (Netherlands) study started in 1990. For 5,443 participants, BZD use during the 15 years from 1990 to 2005 was compared to dementia screens performed through 2020. Half of the participants had used BZD at some time during the 15-year baseline, and 13% developed dementia. Overall, there was no association between BZD use and dementia risk. However, the use of BZD as an anxiolytic in higher doses was associated with dementia risk (HR=1.3). The authors note that BZD with longer half-life are used as anxiolytics, whereas short half-life BZD are used as sedative-hypnotics. A reduction in hippocampal volume on MRI was also associated with BZD use. Overall, there was no association of BZD use with dementia risk, however, some associations were observed that deserve further study.

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Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial

Nature Medicine

The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with treatment-resistant major depression (TRD) and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized to receive double-blind R-107 doses of 30, 60, 120, or 180 mg, or placebo, twice weekly for 12 weeks. Nonresponders on day 8 exited the study. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation, and minimal dissociation. The most common adverse events were headache, dizziness, and anxiety. R-107 tablets were effective, safe, and well tolerated in patients with TRD, enriched for initial response to R-107 tablets.

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Global status report on alcohol and health and treatment of substance use disorders

World Health Organization

This report utilizes data from the WHO member states to summarize alcohol consumption, its health consequences, and alcohol policies around the world. Overall, there was a decrease in alcohol consumption between 2010 and 2019, but alcohol-related deaths still accounted for 4.7% of all deaths in 2019. Despite the burden, there are still significant gaps in access to and types of treatment available worldwide, with the percentage of patients with substance use disorder receiving care ranging from 1% to 30% in countries that gather that data. The report makes several recommendations to address the concern, including a global advocacy campaign, increased training for health professionals at all levels, international knowledge transfers, and resource mobilization.

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Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths

The New England Journal of Medicine

HEALing (Helping to End Addiction Long-term Initiative) Communities Study (HCS) investigators examined the potential of the community-engaged, data-driven Communities That HEAL (CTH) intervention to reduce the rate of opioid-related overdose deaths in highly affected communities. Intervention communities implemented hundreds of strategies to expand opioid overdose education and naloxone distribution, the use of medications for opioid use disorder, and safety measures for prescription opioid use, as well as communication campaigns to support these efforts. Although there were no significant between-group differences in the rate of opioid-related overdose deaths, the trial showed that the CTH community-engaged intervention, with its leveraging of community coalitions and a data-driven approach, can bring about meaningful progress in implementing evidence-based practices.

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Piloting a Hospital-Based Rapid Methadone Initiation Protocol for Fentanyl

Journal of Addiction Medicine

The epidemic of fentanyl has led to increased opioid tolerance and made traditional dosing for methadone initiation insufficient. In this study, the authors examine an inpatient rapid titration of methadone initiation among patients with opioid use disorder (OUD). The protocol recommended dosing of 60 mg on day 1, 70 mg day 2, 80 mg day 3 and 100 mg day 4-7. After patients with significant underlying medical conditions, benzodiazepine or alcohol use and age >65 were excluded, 25 patients underwent the rapid initiation. No patients in the study experienced an adverse event and while additional research is needed, the study demonstrated the feasibility of rapid initiation of methadone for OUD in select patients in an inpatient setting.

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Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population

Nature Communications

In this retrospective cohort study of patients receiving medication for treatment of obesity, the authors evaluated the association of semaglutide with incidence of and recurrence of alcohol use disorder (AUD). In the cohort patients received semaglutide or non-GLP1RA medications, including naltrexone and topiramate. In matched cohort analysis, patients who received semaglutide had much lower rates of incident AUD (HR=0.5) compared to those receiving non-GLP1RA medications and in sub-analysis comparing semaglutide to naltrexone/topiramate the also had lower incident AUD (HR=0.44). Among those with a history of AUD, semaglutide was also associated with lower recurrence of AUD (HR=0.44) overall and in sub-analysis (HR=0.25). These findings support potential benefit of semaglutide for AUD in a real-world population and need for randomized clinical trials.

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Innovation and adaptation: The rise of a fentanyl smoking culture in San Francisco

Plos One

This is a qualitative study describing the growing practice in the San Francisco area of smoking rather than injecting fentanyl. Fentanyl salts are stable up to 350°C making heating and inhalation more effective than for heroin. Some of the increase in smoking is driven by users’ difficulty finding accessible veins. There is also the perception that smoking presents less of a risk of overdose compared to injection. It is unclear if smoking is safer and overdose deaths continue to rise in San Francisco. Over time a brown residue accumulates that contains a high concentration of drug. The smoking equipment is often used for both methamphetamine and fentanyl so this residue contains an unknown mixture of the history of the drugs consumed. The residue is valued for potency but presents a new overdose risk due to the unknown amounts of drugs it contains.

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Rapid Initiation of Injection Naltrexone for Opioid Use Disorder

JAMA Network

Standard initiation procedures (SP) for extended-release (XR)-naltrexone can be a barrier to initiation for patients. In this stepped-wedge cluster-randomized trial, they compared SP initiation (3-5 days buprenorphine taper, 7-10 days opioid-free) to a rapid procedure (RP) initiation (1 day buprenorphine, 1 day opioid free, 3-4 days ascending dose of oral naltrexone). Patients in the RP group (62.7%) were more likely to receive the initial XR-naltrexone dose (OR 3.6, P<0.001) than the SP group (35.8%). There was not a statistically significant difference between the groups in rate of 2nd and 3rd doses. The study demonstrates that RP for initiation of XR-naltrexone is non-inferior to SP and may lead to shorter in-patient stay.

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