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Clinical Medicine (London, England) May 2023Catatonia is a severe neuropsychiatric syndrome that affects emotion, speech, movement and complex behaviour. It can occur in a wide range of psychiatric and...
Catatonia is a severe neuropsychiatric syndrome that affects emotion, speech, movement and complex behaviour. It can occur in a wide range of psychiatric and neurological conditions, including depression, mania, schizophrenia, autism, autoimmune encephalitis (particularly NMDAR encephalitis), systemic lupus erythematosus, thyroid disease, epilepsy and medication-induced and -withdrawal states. This concise guideline highlights key recommendations from the British Association for Psychopharmacology (BAP) Catatonia Guideline, published in April 2023. Important investigations may include neuroimaging, electroencephalography and assessment for neuronal autoantibodies in serum and cerebrospinal fluid. First-line treatment comprises benzodiazepines and/or electroconvulsive therapy. The benzodiazepine of choice is lorazepam, which is sometimes used in very high doses. Multidisciplinary working between psychiatrists and physicians is often essential. The main limitation of the guidelines is the low quality of the underlying evidence, comprising mainly small observational studies and case reports or series.
Topics: Humans; Benzodiazepines; Catatonia; Electroconvulsive Therapy; Nervous System Diseases; Syndrome
PubMed: 37236789
DOI: 10.7861/clinmed.2023-0113 -
Psychotherapy and Psychosomatics 2022Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory... (Review)
Review
Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.
Topics: Alcoholism; Anxiety; Benzodiazepines; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 35504267
DOI: 10.1159/000524400 -
Nature Jul 2018Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA...
Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1β2γ2 GABA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.
Topics: Benzodiazepines; Bicuculline; Binding, Competitive; Brain Chemistry; Cell Membrane; Cryoelectron Microscopy; Flumazenil; GABA Modulators; Glycosylation; HEK293 Cells; Humans; Immunoglobulin Fab Fragments; Ligands; Models, Molecular; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 29950725
DOI: 10.1038/s41586-018-0255-3 -
Journal of Oral Science Jun 2021Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is... (Review)
Review
Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is expected to be safe and effective for a wide range of patients undergoing intravenous sedation for dental procedures. The aim of this literature review was to evaluate clinical and sedation outcomes for remimazolam, including method of administration, level of sedation at the dose required, and clinical adverse events. An electronic literature search of databases was conducted, and eight articles were selected for inclusion in this review. Onset time from drug administration to optimal sedation level was faster for remimazolam (around 1.5-6.4 min) than for midazolam. Recovery time was significantly shorter for remimazolam than for midazolam and propofol. A study comparing various doses of remimazolam with midazolam found no significant difference in safety. Comparison of a remimazolam group with a propofol group showed that incidences of hypotension (13.0% vs 42.9%, respectively) and respiratory depression (1.1% vs 6.9%, respectively) were significantly lower for remimazolam. Remimazolam appears to be an ideal sedative.
Topics: Benzodiazepines; Humans; Hypnotics and Sedatives; Midazolam
PubMed: 34092775
DOI: 10.2334/josnusd.21-0051 -
Drug and Alcohol Dependence Jul 2019Benzodiazepine misuse is a growing public health problem, with increases in benzodiazepine-related overdose deaths and emergency room visits in recent years. However,...
BACKGROUND
Benzodiazepine misuse is a growing public health problem, with increases in benzodiazepine-related overdose deaths and emergency room visits in recent years. However, relatively little attention has been paid to this emergent problem. We systematically reviewed epidemiological studies on benzodiazepine misuse to identify key findings, limitations, and future directions for research.
METHODS
PubMed and PsychINFO databases were searched through February 2019 for peer-reviewed publications on benzodiazepine misuse (e.g., use without a prescription; at a higher frequency or dose than prescribed). Eligibility criteria included human studies that focused on the prevalence, trends, correlates, motives, patterns, sources, and consequences of benzodiazepine misuse.
RESULTS
The search identified 1970 publications, and 351 articles were eligible for data extraction and inclusion. In 2017, benzodiazepines and other tranquilizers were the third most commonly misused illicit or prescription drug in the U.S. (approximately 2.2% of the population). Worldwide rates of misuse appear to be similar to those reported in the U.S. Factors associated with misuse include other substance use, receipt of a benzodiazepine prescription, and psychiatric symptoms and disorders. Benzodiazepine misuse encompasses heterogeneous presentations of motives, patterns, and sources. Moreover, misuse is associated with myriad poor outcomes, including mortality, HIV/HCV risk behaviors, poor self-reported quality of life, criminality, and continued substance use during treatment.
CONCLUSIONS
Benzodiazepine misuse is a worldwide public health concern that is associated with a number of concerning consequences. Findings from the present review have implications for identifying subgroups who could benefit from prevention and treatment efforts, critical points for intervention, and treatment targets.
Topics: Benzodiazepines; Drug Overdose; Humans; Prescription Drug Misuse; Prescription Drugs; Prevalence; Public Health; Quality of Life; Substance-Related Disorders
PubMed: 31121495
DOI: 10.1016/j.drugalcdep.2019.02.033 -
British Journal of Clinical Pharmacology Feb 2014The benzodiazepines (BZDs) are anxiolytics, hypnotics, anticonvulsants, muscle-relaxants and induce anaesthesia. Adverse effects comprise sedation subjectively and... (Review)
Review
The benzodiazepines (BZDs) are anxiolytics, hypnotics, anticonvulsants, muscle-relaxants and induce anaesthesia. Adverse effects comprise sedation subjectively and cognitive and psychomotor impairment objectively. Complex skills such as driving can be compromised. Paradoxical excitement can have forensic implications. Long term use beyond the licensed durations is common but both efficacy and adverse effects associated with this have been poorly documented. Withdrawal and dependence have excited particular concern, and even polemic. Perhaps a third of long term (beyond 6 months) users experience symptoms and signs on attempting to withdraw - anxiety, insomnia, muscle spasms and tension and perceptual hypersensitivity. Uncommonly, fits or a psychosis may supervene. The patterns following withdrawal vary widely. The usual method of withdrawal is slow tapering but it may not obviate the problems completely. BZDs are also drugs of abuse either on their own or in conjunction with opioids and stimulants. Claims have been made that the use of BZDs is associated with increased mortality. This is a concern in view of the widespread usage of these drugs, particularly in the elderly. All of these factors impinge on the risk : benefit ratio and the severity of the indications. Harm reduction should focus on choice of alternative treatments both psychological and pharmacological. Guidelines emphasise that BZDs are not drugs of first choice and should only be used short term. Schedules are available to educate about methods of withdrawal in current users, emphasising the slow rate of taper. General principles of harm minimization in the addiction field are appropriate to BZD abuse.
Topics: Aged; Anti-Anxiety Agents; Benzodiazepines; Harm Reduction; Humans; Hypnotics and Sedatives; Practice Guidelines as Topic; Practice Patterns, Physicians'; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors
PubMed: 22882333
DOI: 10.1111/j.1365-2125.2012.04418.x -
Korean Journal of Anesthesiology Aug 2022Intravenous anesthetic agents such as midazolam, propofol, and ketamine are routinely used to provide anesthesia and sedation. They have been shown to effectively induce... (Review)
Review
Intravenous anesthetic agents such as midazolam, propofol, and ketamine are routinely used to provide anesthesia and sedation. They have been shown to effectively induce and maintain amnesia, sedation, and hypnosis in various patient groups and clinical settings. However, all anesthetic agents have the potential to cause unwanted side effects such as hemodynamic instability, respiratory depression, or slow recovery due to prolonged post-procedural sedation. Remimazolam, a recently approved benzodiazepine for general anesthesia and procedural sedation in Korea, has been successfully used for these purposes. To date, inconclusive knowledge has been obtained regarding the use of remimazolam in different patient populations and under various surgical conditions. With respect to the specific pharmacokinetic and pharmacodynamic characteristics of remimazolam, the use of remimazolam is expected to increase providing safe general anesthesia and sedation. This review aims to provide an overview of the basic and clinical pharmacology of remimazolam and to compare it with midazolam and propofol.
Topics: Anesthesia, General; Anesthetics, Intravenous; Benzodiazepines; Double-Blind Method; Humans; Hypnotics and Sedatives; Midazolam; Propofol
PubMed: 35585830
DOI: 10.4097/kja.22297 -
The Cochrane Database of Systematic... Mar 2018Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering.
OBJECTIVES
To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use.
SEARCH METHODS
We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions.
AUTHORS' CONCLUSIONS
Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.
Topics: Adult; Antidepressive Agents; Aspartic Acid; Benzodiazepines; Buspirone; Carbamazepine; Ethylamines; Flumazenil; Homeopathy; Humans; Imidazoles; Lithium Compounds; Melatonin; Paroxetine; Pregabalin; Progesterone; Pyridines; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Sulfides; Withholding Treatment
PubMed: 29543325
DOI: 10.1002/14651858.CD011481.pub2 -
JAMA Neurology Sep 2022Acute vertigo can be disabling. Antihistamines and benzodiazepines are frequently prescribed as "vestibular suppressants," but their efficacy is unclear. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Acute vertigo can be disabling. Antihistamines and benzodiazepines are frequently prescribed as "vestibular suppressants," but their efficacy is unclear.
OBJECTIVE
To assess the efficacy of antihistamines and benzodiazepines in the treatment of acute vertigo from any underlying cause.
DATA SOURCES
We searched the PubMed, CENTRAL, EMBASE, CINAHL, Scopus, and ClinicalTrials.gov databases from inception to January 14, 2019, without language restrictions. Bibliographies of the included studies and relevant reviews were also screened.
STUDY SELECTION
We included randomized clinical trials (RCTs) comparing antihistamine or benzodiazepine use with another comparator, placebo, or no intervention for patients with a duration of acute vertigo for 2 weeks or less. Studies of healthy volunteers, prophylactic treatment, or induced vertigo were excluded, as were studies that compared 2 medications from the same class.
DATA EXTRACTION AND SYNTHESIS
Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, data were extracted and risk of bias was assessed by 2 authors independently for each study. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The predefined primary outcome was change in 10- or 100-point vertigo or dizziness visual analog scale (VAS) scores at 2 hours after treatment. Secondary outcomes included change in nausea VAS scores at 2 hours, use of rescue medication at 2 hours, and improvement or resolution of vertigo at 1 week or 1 month.
RESULTS
Of the 27 trials identified in the systematic review, 17 contributed to the quantitative meta-analysis and involved a total of 1586 participants. Seven trials with a total of 802 participants evaluated the primary outcome of interest: single-dose antihistamines resulted in significantly more improvement on 100-point VAS scores compared with benzodiazepines (difference, 16.1 [95% CI, 7.2 to 25.0]) but not compared with other active comparators (difference, 2.7 [95% CI, -6.1 to 11.5]). At 1 week and 1 month, neither daily benzodiazepines nor antihistamines were reported to be superior to placebo. RCTs comparing the immediate effects of medications (at 2 hours) after a single dose generally had a low risk of bias, but those evaluating 1-week and 1-month outcomes had a high risk of bias.
CONCLUSIONS AND RELEVANCE
Moderately strong evidence suggests that single-dose antihistamines provide greater vertigo relief at 2 hours than single-dose benzodiazepines. Furthermore, the available evidence did not support an association of benzodiazepine use with improvement in any outcomes for acute vertigo. Other evidence suggested that daily antihistamine use may not benefit patients with acute vertigo. Larger randomized trials comparing both antihistamines and benzodiazepines with placebo could better clarify the relative efficacy of these medications.
Topics: Benzodiazepines; Histamine Antagonists; Humans; Vertigo
PubMed: 35849408
DOI: 10.1001/jamaneurol.2022.1858 -
International Journal of Environmental... Sep 2021Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major... (Review)
Review
Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk-benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70-80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.
Topics: Acceptance and Commitment Therapy; Anxiety Disorders; Benzodiazepines; Cognitive Behavioral Therapy; Humans; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome
PubMed: 34639523
DOI: 10.3390/ijerph181910222