Individuals Reporting Past 3-month Smoked Stimulant Use Are Placed at Risk for Infection and Injury Amid COVID-19.

OBJECTIVES: Smoking stimulants, such as methamphetamine and "crack" cocaine, can spread infections, including hepatitis C and COVID-19, and lead to injuries, particularly when individuals share or use makeshift pipes. The purpose of the study was to assess the practices of people who inhale ("smoke") stimulants to guide future clinical harm reduction efforts. METHODS: Anonymous surveys were administered to participants reporting inhalation of crack cocaine and/or methamphetamine in the past 3 months. Participants were eligible if they sought services from an outreach team staffed by a municipal syringe service program (SSP) or if they were patients at a low-threshold substance use disorder treatment program, the Massachusetts General Hospital Bridge Clinic. RESULTS: The survey was administered to 68 total participants, 30% of whom were recruited in the Massachusetts General Hospital Bridge Clinic and 70% through SSP outreach. Unsafe smoking practices were reported by 93% of participants. Among the 46% of participants surveyed who both smoked and injected stimulants, 61% of those participants stated that they injected instead of smoked stimulants because of lack of access to pipes. Amid COVID-19, 35% of participants adopted safer smoking practices. Most participants reported that they would be more likely to attend an SSP or health center if pipes were provided. CONCLUSIONS: Inhalational practices that place participants at risk of injury and illness are common. Providing safer smoking equipment may promote health and engage individuals in care.

Growing Role of Gabapentin in Opioid-Related Overdoses Highlights Misuse Potential and Off-label Prescribing Practices.

This Medical News article discusses a trend of gabapentin misuse and harms, including fatal overdoses.

Fluvoxamine and Amantadine: Central Nervous System Acting Drugs Repositioned for COVID-19 as Early Intervention.

BACKGROUND: As the World faces unprecedented pandemic caused by SARS-CoV-2 virus, repositioning of existing drugs to treatment of COVID-19 disease is urgently awaited, provided that high quality scientific evidence supporting safety and efficacy in this new indication is gathered. Efforts concerning drugs repositioning to COVID-19 were mostly focused on antiviral drugs, or drugs targeting the late phase of the disease. METHODS: Based on published research, the pharmacological activities of fluvoxamine and amantadine, two well-known drugs widely used in clinical practice for psychiatric and neurological diseases, respectively, have been reviewed, with a focus on their potential therapeutic importance in the treatment of COVID-19. RESULTS: Several preclinical and clinical reports were identified suggesting that these two drugs might exert protective effects in the early phases of COVID-19. CONCLUSION: Preclinical and early clinical evidence are presented indicating that these drugs hold promise to prevent COVID-19 progression when administered early during the course of infection.

Psychotropic medication prescribing during the COVID-19 pandemic.

ABSTRACT: This study examined changes in psychotropic medication use associated with the early months of the coronavirus disease 2019 (COVID-19) pandemic. Using Kaiser Permanente Northern California electronic health records, the authors identified adult patients with fills for psychotropic medications and a non-psychotropic comparator (statins) in the 13 weeks before and after the first-known COVID-19-related death in California (March 4, 2020). Generalized estimating equations were used to derive relative risk ratios (RRR) for medication fills compared with the prior year. Analyses were stratified by new and continued fills and patient characteristics. Among 2,405,824 patients, the mean (SD) age was 49.8 (17.9) years; 52.9% were female; 47.9% identified as White; 8.0% and 7.9% had anxiety and depression disorder diagnoses, respectively. Accounting for secular trends, in the 13 weeks following March 4, 2020, there were increased fills for trazodone (RRR = 1.03, 95% CI = 1.02, 1.04), decreased fills for benzodiazepines (RRR = 0.95, 95% CI = 0.94, 0.96) and hypnotics (RRR = 0.97, 95% CI = 0.96, 0.99), and stable fills for antidepressants (RRR = 1.00, 95% CI = 0.99, 1.00). Relative rates of new fills decreased across most medication classes and continued fills either remained stable or demonstrated non-clinically significant decreases. Patients aged ≥65 years demonstrated decreased fills for most medication classes. In the first 13 weeks of the COVID-19 pandemic, fills for most psychotropic medications remained constant or showed small changes relative to the previous year. Continued (compared with new) fills accounted for observed increases in some medication classes. Older adults demonstrated decreased fills of most medications.

Changes in Purchases for Intensive Care Medicines During the COVID-19 Pandemic: A Global Time Series Study.

BACKGROUND: Drug supply disruptions have increased during the COVID-19 pandemic, especially for medicines used in the ICU. Despite reported shortages in wealthy countries, global analyses of ICU drug purchasing during COVID-19 are limited. RESEARCH QUESTION: Has COVID-19 impacted global drug purchases of first-, second-, and third-choice agents used in intensive care? STUDY DESIGN AND METHODS: We conducted a cross-sectional time series study in a global pharmacy sales dataset comprising approximately 60% of the world's population. We analyzed pandemic-related changes in units purchased per 1,000 population for 69 ICU agents. Interventional autoregressive integrated moving average models tested for significant changes when the pandemic was declared (March 2020) and during its first stage from April through August 2020, globally and by development status. RESULTS: Relative to 2019, ICU drug purchases increased by 23.6% (95% CI, 7.9%-37.9%) in March 2020 (P < .001) and then decreased by 10.3% (95% CI, -16.9% to -3.5%) from April through August (P = .006). Purchases for second-choice medicines changed the most, especially in developing countries (eg, 29.3% increase in March 2020). Despite similar relative changes (P = .88), absolute purchasing rates in developing nations remained low. The observed decrease from April through August 2020 was significant only in developed countries (-13.1%; 95% CI, -17.4% to -4.4%; P < .001). Country-level variation seemed unrelated to expected demand and health care infrastructure. INTERPRETATION: Purchases for intensive care medicines increased globally in the month of the COVID-19 pandemic declaration, but before peak infection rates. These changes were most pronounced for second-choice agents, suggesting that inexpensive, generic medicines may be purchased more easily in anticipation of pandemic-related ICU surges. Nevertheless, disparities in access persisted. Trends seemed unrelated to expected demand, and decreased purchasing from April through August 2020 may suggest overbuying. National and international policies are needed to ensure equitable drug purchasing during future pandemics.

In silico drug repurposing in COVID-19: A network-based analysis.

The SARS-CoV-2 pandemic is a worldwide public health emergency. Despite the beginning of a vaccination campaign, the search for new drugs to appropriately treat COVID-19 patients remains a priority. Drug repurposing represents a faster and cheaper method than de novo drug discovery. In this study, we examined three different network-based approaches to identify potentially repurposable drugs to treat COVID-19. We analyzed transcriptomic data from whole blood cells of patients with COVID-19 and 21 other related conditions, as compared with those of healthy subjects. In addition to conventionally used drugs (e.g., anticoagulants, antihistaminics, anti-TNFα antibodies, corticosteroids), unconventional candidate compounds, such as SCN5A inhibitors and drugs active in the central nervous system, were identified. Clinical judgment and validation through clinical trials are always mandatory before use of the identified drugs in a clinical setting.

Are central nervous system drugs displaying anti-inflammatory activity suitable for early treatment of COVID-19?

The majority of COVID-19 cases are only mildly or moderately symptomatic, but in some patients excessive inflammatory response becomes the dominant factor of disease progression to the advanced stage, with high mortality. Treatment with anti-inflammatory drugs either does not prevent disease progression (non-steroidal anti-inflammatory drugs [NSAIDs], colchicine), or is recommended only at the advanced disease stage (dexamethasone). Fluvoxamine and amantadine are drugs used to treat neurological and psychiatric diseases. Fluvoxamine is a selective serotonin uptake inhibitor, whereas amantadine is an old antiviral variably influencing brain neurotransmitter systems, and repurposed to Parkinson's disease. Both drugs are agonists of sigma-1 receptors located in the endoplasmic reticulum, which effect seems responsible for their anti-inflammatory activity. Moreover, amantadine was found to dampen the expression of cathepsin-L, a lysosomal enzyme implicated in SARS-CoV-2 virus entry to target cells. In two small controlled clinical trials, early treatment of SARS-CoV-2-infected persons with fluvoxamine fully prevented COVID-19 symptoms. Anecdotal evidence shows that amantadine may be similarly effective. Both drugs are easily available, inexpensive and have favorable safety profiles. Clinical trials evaluating their efficacy as much-needed post-exposure prophylaxis and early treatment of COVID-19 are ongoing.

Increasing diversion of prescribed benzodiazepines and Z-drugs to new psychoactive substances.

ABSTRACT: Over the last few years reports have indicated an increase in the number, type and availability of new psychoactive substances belonging to the benzodiazepine class. These molecules may pose high risks to users, since the majority have never undergone clinical trials or tests so their pharmacology and toxicology is largely unknown. However the new drug scenario emerging from the COVID-19 global pandemic seems to play a role in increasing the diversion of prescribed benzodiazepines and Z-drug. A brief presentation of this phenomenon is hereby presented. The awareness and response activities at national and international levels related to this issue should be enforced.

Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor.

The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The escalating number of SARS-CoV-2-infected individuals has conferred the viral spread with the status of global pandemic. However, there are no prophylactic or therapeutic drugs available on the market to treat COVID-19, although several drugs have been approved. Recently, two articles using the comparative viral-human protein-protein interaction map revealed that the sigma-1 receptor in the endoplasmic reticulum plays an important role in SARS-CoV-2 replication in cells. Knockout and knockdown of SIGMAR1 (sigma-1 receptor, encoded by SIGMAR1) caused robust reductions in SARS-CoV-2 replication, which indicates that the sigma-1 receptor is a key therapeutic target for SARS-CoV-2 replication. Interestingly, a recent clinical trial demonstrated that treatment with the antidepressant fluvoxamine, which has a high affinity at the sigma-1 receptor, could prevent clinical deterioration in adult outpatients infected with SARS-CoV-2. In this review, we discuss the brief history of the sigma-1 receptor and its role in SARS-CoV-2 replication in cells. Here, we propose repurposing of traditional central nervous system (CNS) drugs that have a high affinity at the sigma-1 receptor (i.e., fluvoxamine, donepezil, ifenprodil) for the treatment of SARS-CoV-2-infected patients. Finally, we discussed the potential of other CNS candidates such as cutamesine and arketamine.

CNS Penetration Ability: A Critical Factor for Drugs in the Treatment of SARS-CoV-2 Brain Infection.

Now, it has been evidenced that Covid19 (SARS-CoV-2) infects the brain tissues. Along with this, a challenge has been raised for research professionals to find effective drugs for its treatment since the recent spread of this virus from Wuhan, China. Targeting the treatment of brain infection, it has also been a challenge that the clinical drug should have good CNS penetration ability to cross the blood-brain barrier.