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Current Neuropharmacology 2020NPS belonging to the benzodiazepine (BZD) class, e.g., 'legal/designer BZDs'/'research chemicals', have recently emerged in the drug (mainly online/virtual) market. (Review)
Review
BACKGROUND
NPS belonging to the benzodiazepine (BZD) class, e.g., 'legal/designer BZDs'/'research chemicals', have recently emerged in the drug (mainly online/virtual) market.
OBJECTIVE
While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians'/public health knowledge/awareness, to incentive harm reduction strategies.
METHOD
A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the 'new BZDs' so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/ toxicological data, including psychonauts' online trip reports.
RESULTS
First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds.
CONCLUSION
Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.
Topics: Benzodiazepines; Databases, Bibliographic; Designer Drugs; Humans; Molecular Structure; Psychotropic Drugs; Publications; Risk Assessment; Substance-Related Disorders
PubMed: 31933443
DOI: 10.2174/1570159X18666200110121333 -
Journal of Psychiatric Research Sep 2020Benzodiazepines are among the most commonly prescribed psychiatric medications and have the potential for misuse. People with psychiatric disorders may have a heightened...
Benzodiazepines are among the most commonly prescribed psychiatric medications and have the potential for misuse. People with psychiatric disorders may have a heightened liability to the reinforcing effects of benzodiazepines. Yet, the prevalence of benzodiazepine misuse in psychiatric care settings is not well characterized. The aim of the current study was to characterize the prevalence and correlates of benzodiazepine misuse in a sample of adults receiving psychiatric treatment (N = 589). The majority of participants reported a lifetime history of benzodiazepine prescription (68%) and 26% reported a lifetime history of misuse (defined as use without a prescription or at a dose or frequency higher than prescribed). Multivariable analyses indicated that history of a benzodiazepine prescription and drug use problems were significantly associated with lifetime benzodiazepine misuse. People with a history of benzodiazepine prescription had four times higher odds of misusing benzodiazepines and the primary source of misused benzodiazepines was from family or friends. Results suggest that benzodiazepine misuse is not exclusive to substance use disorder populations. The misuse of benzodiazepines should be assessed in psychiatric settings. Further research is needed to understand the impact of benzodiazepine misuse in this population and to develop tools to identify those at risk for misuse.
Topics: Adult; Benzodiazepines; Humans; Prescription Drug Misuse; Prevalence; Psychotherapy; Substance-Related Disorders
PubMed: 32516628
DOI: 10.1016/j.jpsychires.2020.05.020 -
Revista Medica de Chile Mar 2017Growing information has emphasized the risk of benzodiazepines (BZD), particularly among the elderly. However, the information available in Latin America is scarce. (Review)
Review
BACKGROUND
Growing information has emphasized the risk of benzodiazepines (BZD), particularly among the elderly. However, the information available in Latin America is scarce.
AIM
to review the available information on the use of BZD in older adults in Latin America to achieve an overview of the information currently available, and a thorough understanding of this phenomenon in our region.
METHODS
A systematic review with MeSH terms elderly, latinamerican and benzodiazepines was performed in PubMed and with each Latin American country. A search in databases SciELO and LILACS was also performed. In all, 126 items of finally selected 21 that met the inclusion criteria.
RESULTS
Studies show that consumption of benzodiazepines in the elderly population in Latin America is high, with a preponderance of long half-life benzodiazepines in women, and frequent self-medication.
CONCLUSIONS
The revised articles establish the importance of further study of the phenomenon of the use of benzodiazepines in our elderly population. Strikingly, scientific information is scarce, with most studies coming from only one country (Brazil). Moreover, most of them are transversal and descriptive, with few studies that explore long-term side effects, or specific hypotheses. Further studies should address these important issues.
Topics: Age Factors; Aged; Aged, 80 and over; Benzodiazepines; Female; Humans; Latin America; Male; Middle Aged; Socioeconomic Factors
PubMed: 28548192
DOI: 10.4067/S0034-98872017000300009 -
Drug Design, Development and Therapy 2022Remimazolam is a novel short-acting γ-aminobutyric acid (GABA) receptor agonist with typical characteristics of benzodiazepine sedative drugs, nonorgan-dependent... (Review)
Review
Remimazolam is a novel short-acting γ-aminobutyric acid (GABA) receptor agonist with typical characteristics of benzodiazepine sedative drugs, nonorgan-dependent metabolism, long-term infusion without accumulation, and no injection pain. It is quite different from the other current sedative drugs and has broad prospects for application. It has been established that the metabolites of remimazolam are inactive, and the interactions with other drugs are weak with slight cardiopulmonary suppressive effects, showing good effectiveness and safety. During the 2-year period that it has been on the market, remimazolam has been used in multiple clinical scenarios, such as the induction and maintenance of general anesthesia and sedation in outpatient minor procedures or examinations. However, it's use has also prompted widespread concern around the world. Therefore, given its short- and rapid-acting, controllable characteristics remimazolam deserves in-depth study in order for it to be used in fast-track surgery, comfort diagnosis and treatment. Notably, such agents might be of great significance, especially in elderly individuals, patients with critical diseases or patients with liver and kidney insufficiency. The current study reviews recent clinical studies (2015-2022) on remimazolam and summarizes the characteristics of its applications. Specifically, the use of remimazolam in some specific populations are described. This study attempts to provide scientific support for the clinical application of this novel sedative drug in the field of anesthesia.
Topics: Aged; Anesthesiology; Benzodiazepines; Humans; Hypnotics and Sedatives; gamma-Aminobutyric Acid
PubMed: 36213379
DOI: 10.2147/DDDT.S375957 -
La Clinica Terapeutica Mar 2021Over the last few years reports have indicated an increase in the number, type and availability of new psychoactive substances belonging to the benzodiazepine class....
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.
Topics: Benzodiazepines; COVID-19; Central Nervous System Agents; Humans; Prescription Drug Diversion; Substance-Related Disorders
PubMed: 33763670
DOI: 10.7417/CT.2021.2296 -
Swiss Medical Weekly 2018Hospitalisation influences drug therapy in ambulatory care and this influence is generally negatively perceived. The few studies that have explored changes in... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
Hospitalisation influences drug therapy in ambulatory care and this influence is generally negatively perceived. The few studies that have explored changes in benzodiazepine or sleep medication use as a function of hospitalisation failed to precisely determine the hospital's role in initiating, continuing and discontinuing these drugs on a valid basis. The aim of the study was to ascertain the overall influence of hospitalisation on the prescription of benzodiazepines and Z-drugs in outpatient care with a special focus on the role of different hospital departments and drug classes.
METHODS
In a secondary data analysis, we used prescription data for 181 037 patients who visited 127 hospitals and compared the numbers of patients with prescriptions of benzodiazepines and Z-drugs 50 days before and 50 or 100 days after hospitalisation.
RESULTS
The proportion of patients who received benzodiazepines or Z-drugs increased from 3.1% before admission to 3.6% at 50 days after discharge and fell to the former level after an additional 50 days. A multivariable logistic regression showed that gender and department had an additional impact on these results. Of those patients without a prescription for a benzodiazepine or Z-drug before admission, 0.6% received a prescription in both time-windows after discharge. Of those patients who were prescribed a benzodiazepine, 38.0% received short-acting substances and 40.3% received long-acting substances before hospitalisation. After hospitalisation, these rates changed to favour short-acting substances (44.4% and 34.4%, respectively).
CONCLUSIONS
The hospital effect on initiating and increasing hypnotic or sedative drug use seems to be only moderate and temporary. A change in favour of short-acting substances is even welcome. In less than 1% of patients, the hospital initiated the continuous use of benzodiazepines and Z-drugs, which may put pressure on primary care physicians. However, the widespread use of these drugs in hospitals does not seem to be continued on a large scale in primary care.
Topics: Benzodiazepines; Drug Prescriptions; Female; Hospitalization; Humans; Hypnotics and Sedatives; Male; Middle Aged; Patient Discharge; Primary Health Care; Sex Factors; Time Factors
PubMed: 29442341
DOI: 10.4414/smw.2018.14590 -
Drug and Alcohol Review Sep 2023There is concern around non-prescribed benzodiazepine use, particularly with increasing detections of counterfeit products containing high-risk novel compounds. The aims...
INTRODUCTION
There is concern around non-prescribed benzodiazepine use, particularly with increasing detections of counterfeit products containing high-risk novel compounds. The aims of this study were to investigate how and which non-prescribed benzodiazepines are being sourced; forms, appearance and packaging; and awareness of risks associated with non-prescribed benzodiazepines.
METHODS
Data were collected from a sample of Australians who inject drugs or use ecstasy and/or other illicit stimulants on a monthly or more frequent basis, and who reported past 6-month use of non-prescribed benzodiazepines (n = 235 and n = 250, respectively). Data were collected on source, diversion from a known/trusted prescription, product name and aesthetic characteristics for the last non-prescribed benzodiazepine obtained.
RESULTS
Amongst participants who injected drugs, 71% reported that their last non-prescribed benzodiazepines were diverted from a known/trusted prescription, compared to 59% of participants who used ecstasy/other stimulants. Sourcing via cryptomarkets was rare. Across both samples, the majority reported last obtaining substances sold/marketed as diazepam or alprazolam. Participants sourcing via non-diverted means were twice as likely to obtain alprazolam. Known sourcing of novel compounds was rare. Amongst participants who used ecstasy/other stimulants, 36% reported confidence in the content/dose of non-prescribed benzodiazepines even when the source is unknown.
DISCUSSION AND CONCLUSIONS
Most participants obtained substances sold as classic/registered benzodiazepines, mostly via diverted prescriptions, with a substantial minority potentially unaware of counterfeits circulating. While diverted use undeniably presents risks, tightening of prescriptions in Australia could inadvertently lead to greater supply of novel benzodiazepines as seen internationally, reinforcing prioritisation of demand and harm reduction strategies.
Topics: Adult; Female; Humans; Male; Middle Aged; Young Adult; Alprazolam; Australia; Benzodiazepines; Chemical Safety; Consumer Product Safety; Controlled Substances; Counterfeit Drugs; Diazepam; Drug Misuse; Drug Packaging; Drugs, Generic; Illicit Drugs; Interviews as Topic; Marketing; N-Methyl-3,4-methylenedioxyamphetamine; Patient Harm; Patient Medication Knowledge; Prescription Drug Monitoring Programs; Risk; Self Report; Uncertainty
PubMed: 37490407
DOI: 10.1111/dar.13722 -
Advances in Therapy Jun 2020Controversy and uncertainty exist about the use of benzodiazepine receptor agonists (BZRAs) in pain management. This article curates available research to determine the... (Review)
Review
INTRODUCTION
Controversy and uncertainty exist about the use of benzodiazepine receptor agonists (BZRAs) in pain management. This article curates available research to determine the appropriate role of BZRAs in the course of pain management, and how prescribers might address these challenges.
METHODS
A narrative review was performed to determine the appropriate role of BZRAs in pain management and to develop practice recommendations. Publications were identified by a search of PubMed, references of retrieved reports, guidelines, and the author's personal files.
RESULTS
BZRAs were found to have analgesic benefit for two pain conditions: burning mouth syndrome and stiff person syndrome. Absence of research, heterogeneity of trials, and small sample sizes precluded drawing conclusions about efficacy of BZRAs for the other 109 pain conditions explored. Data supports the use of BZRAs to treat co-occurring insomnia and anxiety disorders but only when alternatives are inadequate and only for short periods of time (2-4 weeks). The utility of BZRAs is limited by loss of efficacy that may be seen with continued use and adverse reactions including physiologic dependence which develops in 20-100% of those who take these agents for more than a month.
CONCLUSIONS
BZRAs are often used inappropriately in pain management. Their initiation and duration of use should be limited to a narrow range of conditions. When prescribed for 4 weeks or more, patients should be encouraged to discontinue them through a supported, slow tapering process that may take 12-18 months or longer.
Topics: Benzodiazepines; Chronic Pain; Humans; Inappropriate Prescribing; Pain Management
PubMed: 32378069
DOI: 10.1007/s12325-020-01354-6 -
CNS Neuroscience & Therapeutics Jul 2015Clobazam is an oral 1,5-benzodiazepine used worldwide for the treatment of many types of epilepsies, although it is currently only approved for Lennox-Gastaut syndrome... (Review)
Review
Clobazam is an oral 1,5-benzodiazepine used worldwide for the treatment of many types of epilepsies, although it is currently only approved for Lennox-Gastaut syndrome in the USA. This anticonvulsant and anxiolytic therapeutic has repeatedly demonstrated great efficacy and a high safety profile in refractory epilepsy as well as in a few monotherapy trials in both children and adults. Clobazam allosterically activates the GABAA receptor, and it binds less to subunits that mediate sedative effects than other benzodiazepines. It acts quickly, maintaining a therapeutic effect for a long duration due to its active metabolite, N-desmethylclobazam. Dosage is between 5 mg and 40 mg a day, depending on patient weight, efficacy, and tolerability. Efficacy tolerance has not been a problem in the best studies. Clobazam has provided many benefits to epileptic patients. It should be used by clinicians early as an adjuvant therapy in the treatment of refractory epilepsy and even considered as monotherapy in a broad spectrum of epilepsy syndromes.
Topics: Anticonvulsants; Benzodiazepines; Clobazam; Drug Discovery; Epilepsy; Humans
PubMed: 25917225
DOI: 10.1111/cns.12399 -
Journal of Medical Toxicology :... Jan 2023
Topics: Humans; Benzodiazepines; Drug Industry
PubMed: 36414791
DOI: 10.1007/s13181-022-00917-z