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The Primary Care Companion For CNS... Mar 2017To evaluate whether prescribed benzodiazepines affect one's risk of suicide. (Review)
Review
OBJECTIVE
To evaluate whether prescribed benzodiazepines affect one's risk of suicide.
DATA SOURCES
A PubMed search of English-language publications from database inception until October 11, 2016, was conducted using the terms benzodiazepine and suicide. References and related articles were also searched to yield additional publications.
STUDY SELECTION/DATA EXTRACTION
Studies were included if they addressed the relationship between suicidal behavior and the prescribed use of either specific benzodiazepines or benzodiazepines as a class. A total of 17 studies were included in this review.
RESULTS
The majority of studies found that benzodiazepines were associated with increased suicide risk. This finding was consistent across various populations and different types of research, including a placebo-controlled crossover trial, a laboratory model of suicidal behavior, case-control studies regarding completed suicides on inpatient units, and large naturalistic studies.
CONCLUSIONS
Benzodiazepines appear to cause an overall increase in the risk of attempting or completing suicide. Possible mechanisms of prosuicidal effects may include increases in impulsivity or aggression, rebound or withdrawal symptoms, and toxicity in overdose.
Topics: Benzodiazepines; Humans; Risk; Suicide
PubMed: 28257172
DOI: 10.4088/PCC.16r02037 -
Tidsskrift For Den Norske Laegeforening... Mar 2024The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment.
BACKGROUND
The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment.
CASE PRESENTATION
A man in his thirties was submitted to detoxification after reportedly using flubromazolam, a high potency designer benzodiazepine, which he had purchased on the dark web. Extensive drug testing of serum, urine and hair, and the remains in a dropper bottle delivered by the patient, did not reveal flubromazolam or possible metabolites, but did reveal several common drugs of abuse, and 8-aminoclonazolam, a metabolite of clonazolam, another designer benzodiazepine sold on the dark web. The detoxification was uncomplicated. An excessive treatment protocol based on the patient's information, involving high preparedness and increased resources, both clinically and analytically, turned out to be unnecessary.
INTERPRETATION
The drug use and clinical course in this case proved to be more common than the unit prepared for. The case history illustrates both the challenges with users of NPS and the general unpredictability in substance abuse treatment.
Topics: Male; Humans; Benzodiazepines; Designer Drugs; Substance-Related Disorders; Substance Abuse Detection; Psychotropic Drugs
PubMed: 38506014
DOI: 10.4045/tidsskr.23.0668 -
Advances in Therapy May 2022Although benzodiazepines have been used for 6 decades, many questions remain unanswered by research. The lived experiences of those adversely affected long term can...
Although benzodiazepines have been used for 6 decades, many questions remain unanswered by research. The lived experiences of those adversely affected long term can provide insights into how these agents might be more thoughtfully prescribed. Here, perspectives of one such experience encompassing benzodiazepine initiation, ongoing use with adverse consequences and difficult discontinuation are presented through the eyes of an affected individual and a clinician. This experience highlights the importance of limited initiation and duration of use (2-4 weeks) as well as a supported, slow tapering process led by patients. Because researched evidence about deprescribing benzodiazepines is insufficient and because individual experiences vary so widely, it is the patient's expertise-that of her or his lived experience-that should assume a primary role in determining the course and pace of discontinuing these medications.
Topics: Benzodiazepines; Female; Humans; Male; Substance Withdrawal Syndrome
PubMed: 35239167
DOI: 10.1007/s12325-022-02055-y -
Swiss Medical Weekly 2011Benzodiazepines are widely prescribed drugs used to treat anxiety and insomnia, induce muscle relaxation, control epileptic seizures, promote anaesthesia or produce... (Review)
Review
Benzodiazepines are widely prescribed drugs used to treat anxiety and insomnia, induce muscle relaxation, control epileptic seizures, promote anaesthesia or produce amnesia. Benzodiazepines are also abused for recreational purposes and the number of benzodiazepine abusers is unfortunately increasing. Within weeks of chronic use, tolerance to the pharmacological effects can develop and withdrawal becomes apparent once the drug is no longer available, which are both conditions indicative of benzodiazepine dependence. Diagnosis of addiction (i.e. compulsive use despite negative consequences) may follow in vulnerable individuals. Here, we review the historical and current use of benzodiazepines from their original synthesis, discovery and commercialisation to the recent identification of the molecular mechanism by which benzodiazepines induce addiction. These results have identified the mechanisms underlying the activation of midbrain dopamine neurons by benzodiazepines, and how these drugs can hijack the mesocorticolimbic reward system. Such knowledge calls for future developments of new receptor subtype specific benzodiazepines with a reduced addiction liability.
Topics: Benzodiazepines; Dopaminergic Neurons; History, 20th Century; Humans; Mesencephalon; Substance-Related Disorders
PubMed: 22012428
DOI: 10.4414/smw.2011.13277 -
The Cochrane Database of Systematic... Oct 2009Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies... (Review)
Review
BACKGROUND
Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies have been unclear, with some suggesting that benzodiazepines may be useful in controlling non-alcohol related delirium.
OBJECTIVES
To determine the effectiveness and incidence of adverse effects of benzodiazapines in the treatment of non-alcohol withdrawal related delirium.
SEARCH STRATEGY
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February 2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG Specialized Register contains records from major health databases (including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial databases and grey literature sources.
SELECTION CRITERIA
Trials had to be unconfounded, randomized and with concealed allocation of subjects. Additionally, selected trials had to have assessed patients pre- and post-treatment. Where crossover design was present, only data from the first part of the trial were to be examined.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data from included trials. Data were pooled where possible, and were to be analysed using appropriate statistical methods. Odd ratios or average differences were to be calculated. Only "intention to treat" data were to be included.
MAIN RESULTS
Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion.
AUTHORS' CONCLUSIONS
No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.
Topics: Benzodiazepines; Delirium; Dexmedetomidine; Humans; Lorazepam
PubMed: 19821364
DOI: 10.1002/14651858.CD006379.pub3 -
Journal of Affective Disorders May 2020Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the literature to estimate the worldwide use of benzodiazepines before, during and after pregnancy, which could help to estimate benzodiazepine exposure and to prioritize and guide future investigations.
METHODS
We systematically searched Embase, Medline Ovid, Web of Science and Cochrane Central up until July 2019 for studies reporting on benzodiazepine use before (12 months), during and after pregnancy (12 months). Random effects meta-analysis was conducted to calculate pooled prevalence estimates, as well as stratified according to substantive variables.
RESULTS
We identified 32 studies reporting on 28 countries, together reporting on 7,343,571 pregnancies. The worldwide prevalence of benzodiazepine use/prescriptions during pregnancy was 1.9% (95%CI 1.6%-2.2%; I 97.48%). Highest prevalence was found in the third trimester (3.1%; 95%CI 1.8%-4.5%; I 99.83%). Lorazepam was the most frequently used/prescribed benzodiazepine (1.5%; 95%CI 0.5%-2.5%; I 99.87%). Highest prevalence was found in Eastern Europe (14.0%; 95%CI 12.1%-15.9%; I 0.00%).
LIMITATIONS
All analyses revealed considerable heterogeneity.
CONCLUSIONS
Our meta-analysis confirmed that benzodiazepine use before, during and after pregnancy is prevalent. The relatively common use of benzodiazepines with possible risks for both mother and (unborn) child is worrying and calls for prescription guidelines for women, starting in the preconception period. Given the substantial proportion of children exposed to benzodiazepines in utero, future research should continue to study the short- and long-term safety of maternal benzodiazepine use during pregnancy and to explore non-pharmacological alternative treatments.
Topics: Anxiety; Benzodiazepines; Child; Female; Humans; Hypnotics and Sedatives; Pharmaceutical Preparations; Pregnancy; Prevalence
PubMed: 32217339
DOI: 10.1016/j.jad.2020.03.014 -
The Cochrane Database of Systematic... Mar 2017Restless legs syndrome (RLS) is a common disease affecting about 5% to 15% of the population. Symptoms of RLS can be severe in a minority of and can have a major impact... (Review)
Review
BACKGROUND
Restless legs syndrome (RLS) is a common disease affecting about 5% to 15% of the population. Symptoms of RLS can be severe in a minority of and can have a major impact on sleep, mostly sleep initiation, and quality of life. Benzodiazepines are drugs that can induce and maintain sleep and, hence, intuitively are thought to be beneficial to people with RLS. Altough benzodiazepines, particularly clonazepam, are used to treat RLS symptoms, a systematic review done by the American Academy of Sleep Medicine stated that benzodiazepines should not be used as a first-line treatment, although could be used as a coadjuvant therapy.
OBJECTIVES
To evaluate the efficacy and safety of benzodiazepine compared to placebo or other treatment for idiopathic RLS, including unconfounded trials comparing benzodiazepines versus open control.
SEARCH METHODS
In March 2016 we searched CENTRAL, MEDLINE, Embase and LILACS We checked the references of each study and contacted study authors to identify any additional studies. We considered studies published in any language.
SELECTION CRITERIA
Randomised clinical trials of benzodiazepine treatment in idiopathic RLS.
DATA COLLECTION AND ANALYSIS
We did not perform data collection and analysis, since we did not include any studies, MAIN RESULTS: We did not identify any studies that met the inclusion criteria of the review. Two cross-over studies are awaiting classification because the cross-over trials did not give data at the end of the first cross-over period.
AUTHORS' CONCLUSIONS
The effectiveness of benzodiazepines for RLS treatment is currently unknown.
Topics: Benzodiazepines; Humans; Restless Legs Syndrome
PubMed: 28319266
DOI: 10.1002/14651858.CD006939.pub2 -
Molecules (Basel, Switzerland) Jan 2016Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered "privileged structures" since they possess a wide range of biological activities. The first... (Review)
Review
Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered "privileged structures" since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of the molecule and a study of its interaction with DNA. This opened up an intensive synthetic and biological study of the pyrrolo[2,1-c][1,4]benzodiazepines that has culminated in the development of the dimer SJG-136, at present in Phase II clinical trials. The synthetic efforts have brought to light some new synthetic methodology, while the contemporary work is focused on building trimeric pyrrolo[2,1-c][1,4]benzodiazepines linked together by various heterocyclic and aliphatic chains. It is the broad spectrum of biological activities of pyrrolo[1,2-a][1,4]benzodiazepines that has maintained the interest of researchers to date whereas several derivatives of the even less studied pyrrolo[1,2-d][1,4]benzodiazepines were found to be potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The present review is an update on the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines since the last major review of 2011, while the overview of the synthesis of the other two tricyclic isomers is comprehensive.
Topics: Anti-HIV Agents; Antineoplastic Agents; Benzodiazepines; Clinical Trials as Topic; Cyclization; DNA; HIV Infections; Humans; Molecular Structure; Neoplasms; Pyrroles; Structure-Activity Relationship
PubMed: 26828475
DOI: 10.3390/molecules21020154 -
Research in Social & Administrative... Apr 2022Deprescribing of medications such as benzodiazepines and benzodiazepine receptor agonists (z-drugs) can be a complex process that varies across practices, specialties,...
Deprescribing of medications such as benzodiazepines and benzodiazepine receptor agonists (z-drugs) can be a complex process that varies across practices, specialties, and health care systems. Care coordination among healthcare providers, patients, families, and other healthcare system components is critical to achieving high levels of deprescribing and person-centered care. We present a framework for promoting care coordination in the context of benzodiazepine/z-drug deprescribing. Future efforts are needed to study the impact of better care coordination on benzodiazepines/z-drug discontinuation and other outcomes that are important to stakeholders.
Topics: Benzodiazepines; Deprescriptions; Humans; Receptors, GABA-A
PubMed: 34229951
DOI: 10.1016/j.sapharm.2021.06.025 -
The Cochrane Database of Systematic... Nov 2012Because of the high number of people with schizophrenia not responding adequately to monotherapy with antipsychotic agents, the evidence regarding the efficacy and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Because of the high number of people with schizophrenia not responding adequately to monotherapy with antipsychotic agents, the evidence regarding the efficacy and safety of additional medication was examined in a number of clinical trials. One approach to this research question was the use of benzodiazepines, as monotherapy as well as in combination with antipsychotics.
OBJECTIVES
To determine the efficacy, acceptability, and tolerability of benzodiazepines in people with schizophrenia and schizophrenia-like psychoses.
SEARCH METHODS
In February 2011, we updated the literature search of the previous version of this systematic review (last search March 2005). We searched the trial register of the Cochrane Schizophrenia Group (containing methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings). Additionally, we inspected references of all identified studies for further relevant studies and contacted authors of relevant publications in order to obtain missing data from existing trials. We applied no language restrictions.
SELECTION CRITERIA
We included all randomised controlled trials comparing benzodiazepines (as monotherapy or as adjunctive agent) with antipsychotic drugs or placebo for the pharmacological management of schizophrenia and/or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
Review authors (MD and CL) analysed independently the new references of the update-search referring to the inclusion criteria. MD and CL extracted all data from the included trials. For dichotomous outcomes we calculated risk ratios (RR) and their 95% confidence intervals (CI). We analysed continuous data by using mean differences (MD) and their 95% CI. We assessed each pre-selected outcome from the included trials with the risk of bias tool.
MAIN RESULTS
The 2011 update search yielded three further randomised controlled trials. The review currently includes 34 studies with 2657 participants. Most studies were characterised by a small sample size, short duration, and incomplete outcome data reporting.Benzodiazepine monotherapy is compared with placebo in eight trials. The proportion of participants with no clinically important response did not significantly differ between those given benzodiazepines or placebo (N = 382, 6 RCTs, RR 0.67 CI 0.44 to 1.02). The results from the various rating scales applied to assess global and mental state were inconsistent.Fourteen studies examined benzodiazepine monotherapy in comparison with antipsychotic monotherapy. Clinically important treatment response assessment revealed no statistically significant difference between the study groups (30 minutes: N = 44, 1 RCT, RR 0.91 CI 0.58 to 1.43; 60 minutes: N = 44,1 RCT, RR 0.61 CI 0.20 to 1.86; 12 hours: N = 66, 1 RCT, RR 0.75 CI 0.44 to 1.30; pooled short-term studies: N = 112, 2 RCTs, RR 1.48 CI 0.64 to 3.46). Desired sedation occurred significantly more often among participants in the benzodiazepine group than in the antipsychotic group at 20 and 40 minutes. No significant between-group differences could be identified for global and mental state or occurrence of adverse effects.Twenty trials compared benzodiazepine augmentation of antipsychotics with antipsychotic monotherapy. Referring to clinically important response, statistically significant improvement could be demonstrated only for the first 30 minutes of augmentation treatment (30 minutes: 1 RCT, N = 45, RR 0.38 CI 0.18 to 0.80; 60 minutes: N = 45,1 RCT, RR 0.07 CI 0.00 to 1.13; 12 hour: N = 67,1 RCT, RR 0.85 CI 0.51 to 1.41; pooled short-term studies: N = 511, 6 RCTs, RR 0.87 CI 0.49 to 1.54). Analyses of the global and mental state yielded no between-group differences except for desired sedation at 30 as well as 60 minutes (30 minutes: N = 45, 1 RCT, RR 2.25 CI 1.18 to 4.30; 60 minutes: N = 45, 1 RCT, RR 1.39 CI 1.06 to 1.83).
AUTHORS' CONCLUSIONS
There is currently no convincing evidence to confirm or refute the practise of administering benzodiazepines as monotherapy or in combination with antipsychotics for the pharmacological treatment of schizophrenia and schizophrenia-like psychosis. Low-quality evidence suggests that benzodiazepines are effective for very short-term sedation and could be considered for calming acutely agitated people with schizophrenia. Measured by the overall attrition rate, the acceptability of benzodiazepine treatment appears to be adequate. Adverse effects were generally poorly reported. High-quality future research projects with large sample sizes are required to clarify the evidence of benzodiazepine treatment in schizophrenia, especially regarding long-term augmentation strategies.
Topics: Antipsychotic Agents; Benzodiazepines; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 23152236
DOI: 10.1002/14651858.CD006391.pub2