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Nsira, Asma, Ahlem Karoui, Rafik Gharbi, and Moncef Msaddek. "Chemoselectivity of the 1,3-Dipolar Cycloaddition of Some Diazoalkanes with 1,5-Benzodiazepine Derivatives." Journal of Chemical Research 36, no. 3 (March 2012): 152–56. http://dx.doi.org/10.3184/174751912x13300109535030.
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Benzodiazepines are pharmaceutically important synthetic materials. Reaction of the 4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-one with 2-diazopropane (DAP) gave a mixture of the 2-isopropylether of 4-(2-hydroxyphenyl)-3H-1,5-benzodiazepine and 1-isopropyl-4-(2-hydroxyphenyl)-3H-1,5-benzodiazepin-2-one. Whilst diphenyldiazomethane (DPDM) gave 1-benzhydryl-4-(2-hydroxyphenyl)-3H-1,5-benzodiazepin-2-one. Reaction of the corresponding thione with DAP led to the 2-isopropylthioether of 4-(2-hydroxyphenyl)-3H-1,5-benzodiazepine and 1-isopropyl-4-(2-hydroxyphenyl)-1,5-benzodiazepine-2-thione while the reaction with DPDM gave the 2-benzhydrylthioether of 4-(2-hydroxyphenyl)-3H-1,5-benzodiazepine. The characterisation of these prepared - N, - O and - S alkylated benzodiazepines involved 1D and 2D-NMR techniques, mass spectrometry and elemental analysis.
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Rotaru, Luciana Teodora, Paul Nedelea, Renata-Maria Varut, Alina Petrica, Silvia Nica, Catalin Bouros, Diana Cimpoesu, Mihaela Corlade, Mihai Banicioiu Covei, and Marius Novac. "Determining the Influence of Alcohol on the Pharmacological Effect of Benzodiazepines by Molecular Docking Tehnique." Revista de Chimie 70, no. 3 (April 15, 2019): 814–19. http://dx.doi.org/10.37358/rc.19.3.7013.
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Benzodiazepines represents a large category of medications that were originally developed to treat anxiety disorders or issues with anxiety, seizures, and issues with sleeping. The most common drugs abused along with benzodiazepines are other benzodiazepines, prescription pain medications and alcohol. Alcohol and benzodiazepine have a synergistic depressant effect on the central nervous system. Combining alcohol with benzodiazepines can be dangerous practice even if it is engaged in only occasionally. In the present study, using molecular docking technique we followed the binding energy of benzodiazepines with benzodiazepine receptor and efficacy of the flumazenil antidote against benzodiazepine in the presence and absence of alcohol. We realized correlation study of molecular descriptors value of benzodiazepines with benzodiazepine-GABAA complex binding energy.
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Lyukshenko, Natalya I., Roman G. Nikitin, and Yury V. Morozhenko. "New technology to obtain 1-methyl-5-pnenyl-7-chloro- 1,3-dihydro-2H-[1,4]-benzodiazepine-2-one." Butlerov Communications 60, no. 10 (October 31, 2019): 24–31. http://dx.doi.org/10.37952/roi-jbc-01/19-60-10-24.
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At present, benzodiazepine derivatives being used widely, they continue to occupy a leading position among the drugs of the anxiolytic group. Most anxiolytics of the benzodiazepine structure are derivatives of 1,4-benzodiazepine. The basis of the chemical benzodiazepine structure consists of a benzene ring connected to a seven-membered heterocyclic ring containing two nitrogen atoms (diazepine) at positions 1 and 4. All the benzodiazepine derivatives used in the clinic also have a second benzene ring attached to carbon. The presence of a halogen or a nitro group is essential to display its activity. Diazepam (1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H- [1,4] benzodiazepin-2-one) is in the list of necessary and important medicinal products. The urgent issue is the development of a new method to synthesize 1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one that would allow producing the drug in the required quantities and for mass consumption. The search for possible effective ways of synthesizing 1-methyl-5-phenyl-7-chlorine-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one for manufacturing application is of great scientific and practical interest. The purpose of our work is to search for a rational method to synthesize the target product, experimental study of the chemical processes to develop the most optimal methods to produce the product. The technology to produce 1-methyl-5-phenyl-7-chlor-1,3-dihydro-2H-[1,4]-benzodiazepine-2-one on an industrial scale was developed. The synthesis of 2-benzoyl-2',4-dichloro-N-methylacetanilide by condensation of 2-methylamine-5-chlorobenzophenone with chloracetyl chloride in carbon tetrachloride without further treatment of the reaction mass with water and sodium carbonate was developed. The highest yield of 1-methyl-5-phenyl-7-chlorine-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one was shown to be obtained if the cyclization reaction is carried out in isopropyl alcohol. The reaction mixture composition in interaction of 2-benzoyl- 2',4 -dichloro-N-methylacetanilide with urotropin plays the defining role in the formation of the target product.
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Muzaale, Abimereki D., Matthew Daubresse, Sunjae Bae, Nadia M. Chu, Krista L. Lentine, Dorry L. Segev, and Mara McAdams-DeMarco. "Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis." Clinical Journal of the American Society of Nephrology 15, no. 6 (May 26, 2020): 794–804. http://dx.doi.org/10.2215/cjn.13341019.
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Background and objectivesMortality from benzodiazepine/opioid interactions is a growing concern in light of the opioid epidemic. Patients on hemodialysis suffer from a high burden of physical/psychiatric conditions, which are treated with benzodiazepines, and they are three times more likely to be prescribed opioids than the general population. Therefore, we studied mortality risk associated with short- and long-acting benzodiazepines and their interaction with opioids among adults initiating hemodialysis.Design, setting, participants, & measurementsThe cohort of 69,368 adults initiating hemodialysis (January 2013 to December 2014) was assembled by linking US Renal Data System records to Medicare claims. Medicare claims were used to identify dispensed benzodiazepines and opioids. Using adjusted Cox proportional hazards models, we estimated the mortality risk associated with benzodiazepines (time varying) and tested whether the benzodiazepine-related mortality risk differed by opioid codispensing.ResultsWithin 1 year of hemodialysis initiation, 10,854 (16%) patients were dispensed a short-acting benzodiazepine, and 3262 (5%) patients were dispensed a long-acting benzodiazepine. Among those who were dispensed a benzodiazepine during follow-up, codispensing of opioids and short-acting benzodiazepines occurred among 3819 (26%) patients, and codispensing of opioids and long-acting benzodiazepines occurred among 1238 (8%) patients. Patients with an opioid prescription were more likely to be subsequently dispensed a short-acting benzodiazepine (adjusted hazard ratio, 1.66; 95% confidence interval, 1.59 to 1.74) or a long-acting benzodiazepine (adjusted hazard ratio, 1.11; 95% confidence interval, 1.03 to 1.20). Patients dispensed a short-acting benzodiazepine were at a 1.45-fold (95% confidence interval, 1.35 to 1.56) higher mortality risk compared with those without a short-acting benzodiazepine; among those with opioid codispensing, this risk was 1.90-fold (95% confidence interval, 1.65 to 2.18; Pinteraction<0.001). In contrast, long-acting benzodiazepine dispensing was inversely associated with mortality (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72 to 0.99) compared with no dispensing of long-acting benzodiazepine; there was no differential risk by opioid dispensing (Pinteraction=0.72).ConclusionsCodispensing of opioids and short-acting benzodiazepines is common among patients on dialysis, and it is associated with higher risk of death.
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Williams, Hugh, Doug Handyside, Kirsty Bashford, and Adenekan Oyefeso. "Service response to benzodiazepine use in opiate addicts: a national postal survey." Irish Journal of Psychological Medicine 22, no. 1 (March 2005): 15–18. http://dx.doi.org/10.1017/s0790966700008739.
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AbstractObjectives: The study reports on benzodiazepine use among opiate dependent patients attending National Health Service community prescribing services and examines current practice in the clinical management of benzodiazepine dependence.Method: A postal questionnaire survey of 174 NHS substance misuse services in England and Wales.Results: A 71% response rate was achieved. Services estimated the prevalence of benzodiazepine use to be 40% and the prevalence of benzodiazepine dependence to be less than 25% among opiate dependent patients in treatment. Illicit supplies (street) and general practitioners were regarded as the most common source of benzodiazepines. The most commonly reported reasons for benzodiazepine use were for the direct intoxicating effects and for the treatment of anxiety/insomnia. The majority of services (93,75%) reported prescribing benzodiazepines to patients for benzodiazepine detoxification while 43 (35%) reported prescribing for benzodiazepine maintenance treatment. The variations in benzodiazepine prescribing practices across services are described.Conclusions: Benzodiazepine use remains common among opiate addicts in contact with treatment services. The majority of services surveyed reported prescribing benzodiazepines but there was much variation in clinical practice nationally. There is need for further research to identify effective treatment approaches for comorbid benzodiazepine dependence in opiate misusers.
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van der Sluiszen, Nick, Annemiek Vermeeren, Stefan Jongen, Frederick Vinckenbosch, and Johannes Ramaekers. "Influence of Long-Term Benzodiazepine use on Neurocognitive Skills Related to Driving Performance in Patient Populations: A Review." Pharmacopsychiatry 50, no. 05 (July 4, 2017): 189–96. http://dx.doi.org/10.1055/s-0043-112755.
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AbstractAcute benzodiazepine intoxication produces severe impairment of neurocognitive skills related to driving. It is less clear whether such impairments also occur in patients who use benzodiazepines chronically. The current review evaluated neurocognitive skills of long-term benzodiazepine users and addressed 2 major questions: do long-term users develop tolerance for the impairing effects of benzodiazepines on neurocognitive performance, and if so, does tolerance warrant a change in driver fitness classification systems that currently deem users of benzodiazepines unfit to drive? Neurocognitive impairments were reported in patients who on average used benzodiazepines for 5–15 years. In addition, sensitivity to acute benzodiazepine impairment decreased in long-term users, suggesting (partial) tolerance. Definitions of clinical relevance of neurocognitive impairments in long-term users and how these were affected by duration of benzodiazepine use were generally lacking. Also, sensitivity of neurocognitive tasks to drug effects and their validity to predict fitness to drive were generally unknown. Because of these limitations, no firm conclusion can be drawn regarding a re-classification of long-term benzodiazepine effects on driver fitness.
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Grønbæk, Lisbet, Hugh Watson, Hendrik Vilstrup, and Peter Jepsen. "Benzodiazepines and risk for hepatic encephalopathy in patients with cirrhosis and ascites." United European Gastroenterology Journal 6, no. 3 (August 23, 2017): 407–12. http://dx.doi.org/10.1177/2050640617727179.
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Background There is limited evidence to support the belief that benzodiazepines increase cirrhosis patients’ risk of hepatic encephalopathy (HE). Objective We aimed to examine the association between benzodiazepine use and HE development in cirrhosis patients. Methods We used data on 865 cirrhosis patients with ascites from three trials to study the effect of benzodiazepine use on development of first-time HE. For each patient, we classified periods of benzodiazepine use by the number of days since initiation. We used Cox regression to compare the risk of HE in current benzodiazepine users vs. non-users adjusting for confounders. Results Cirrhosis patients were not at increased risk of HE for the first two days of benzodiazepine use, but then faced a five-fold increased risk of HE during days 3 to 10 of benzodiazepine use. The risk of HE was not increased for those who had been using benzodiazepines for more than 28 days. Conclusion Cirrhosis patients who had begun using benzodiazepines between 3 and 10 days previously had a markedly increased risk of developing first-time HE. Cirrhosis patients who had been using benzodiazepines for just one or two days or continued use for more than 28 days did not have such an excess risk.
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Lutz, Eric William, and Christopher Hines. "Recurrent clonazepam withdrawal delirium in a postoperative neurosurgical patient: a case report." BMJ Case Reports 14, no. 6 (June 2021): e240804. http://dx.doi.org/10.1136/bcr-2020-240804.
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We present a case of benzodiazepine withdrawal delirium in a middle-aged man undergoing spinal surgery. Benzodiazepines were stopped prior to surgery and on postoperative day 4, the patient exhibited significant paranoia, hyperarousal and ideas of reference. Patient’s symptoms resolved after reintroduction of his benzodiazepines. It is important to include benzodiazepine withdrawal in the differential diagnosis for acute delirium even in those patients taking low or moderate doses. Benzodiazepine withdrawal delirium typically responds rapidly to restarting benzodiazepines. In patients with known discontinuation issues, early consultation with consult-liaison psychiatry and preoperative planning for early medication re-initiation is paramount.
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Summers, J., and K. W. Brown. "Benzodiazepine prescribing in a psychiatric hospital." Psychiatric Bulletin 22, no. 8 (August 1998): 480–83. http://dx.doi.org/10.1192/pb.22.8.480.
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Using a case note study, this paper presents a longitudinal survey of the effect of psychiatric inpatient care on benzodiazepine prescribing. Standards were proposed to assess the quality of this prescribing. Based on these standards, the study shows inappropriate use of benzodiazepines. Following admission, there was an increase in the number of patients prescribed benzodiazepines and in the number of benzodiazepines prescribed. Of the benzodiazepines withdrawn, most were contrary to the proposed standard. The quality of drug history showed little emphasis being placed on rationalising benzodiazepine prescribing. The issue of how benzodiazepines should be handled during psychiatric admission is discussed.
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Cooper, Michael, Marc Safran, and Mark Eberhardt. "Caffeine Consumption among Adults on Benzodiazepine Therapy: United States 1988–1994." Psychological Reports 95, no. 1 (August 2004): 183–91. http://dx.doi.org/10.2466/pr0.95.1.183-191.
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The concomitant use of benzodiazepines and caffeine was studied to learn if caffeine consumption varied as a function of benzodiazepine use. Caffeine may antagonize the effects of benzodiazepine and even relatively small amounts can aggravate symptoms associated with anxiety disorders. In addition, caffeine can cause or aggravate insomnia, one of the main reasons cited for use by the subjects in this analysis. Given this, there would seem to be sufficient reason for at least some users of benzodiazepines to consider, with their physicians, avoiding or limiting caffeine consumption. Data from the Third National Health and Nutrition Examination Survey were analyzed to obtain a nationally representative sample of benzodiazepine users. Subjects included 253 individuals (64% women) whose median age was 54 yr. Approximately 88% of benzodiazepine users reported caffeine consumption in the 24-hr. Dietary Recall. 26% of benzodiazepine users and 23% of nonusers reported consuming greater than 250 mg of caffeine during the 24-hr. reference period. In regression analyses, no significant relationships were found between reported caffeine consumption and benzodiazepine use. This study suggests that users and nonusers of benzodiazepines ingest similar amounts of caffeine even though some users should probably avoid or limit caffeine use.
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De Maricourt, P., P. Gorwood, Th Hergueta, A. Galinowski, R. Salamon, A. Diallo, C. Vaugeois, J. P. Lépine, J. P. Olié, and O. Dubois. "Balneotherapy Together with a Psychoeducation Program for Benzodiazepine Withdrawal: A Feasibility Study." Evidence-Based Complementary and Alternative Medicine 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/8961709.
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Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (%) use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction.
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Cosh, Ayla, and Helen Carslaw. "Managing benzodiazepine dependence." InnovAiT: Education and inspiration for general practice 10, no. 11 (August 22, 2017): 671–78. http://dx.doi.org/10.1177/1755738017715275.
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Benzodiazepines have a variety of clinical indications. Benzodiazepines are used as anxiolytics, hypnotics, anticonvulsants, muscle relaxants and in assisting alcohol withdrawal. This article aims to give a general overview of benzodiazepine use, prescribing issues and approaches to managing dependence.
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Bužančić, Iva, Tajana Iva Pejaković, and Maja Ortner Hadžiabdić. "A Need for Benzodiazepine Deprescribing in the COVID-19 Pandemic: A Cohort Study." Pharmacy 10, no. 5 (September 23, 2022): 120. http://dx.doi.org/10.3390/pharmacy10050120.
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The COVID-19 pandemic has had a negative impact on patients’ mental health. The aim of this study was to explore whether the pandemic influenced the use and prescription of benzodiazepines and increased the need for community pharmacist involvement in counselling on deprescribing. Electronic prescription-related data from one pharmacy in Croatia were retrospectively collected for the COVID-19 period (April 2020 to March 2021) and compared with pre-COVID-19 (April 2019 to March 2020) data. Data were collected for patients diagnosed with anxiety disorders who filled out more than one prescription for benzodiazepines, and included age, sex, number of medicines, benzodiazepines, and comorbidities. A total of 1290 benzodiazepine users were identified; of these, 32.87% started using benzodiazepines during the COVID-19 period, while 35.2% continued with benzodiazepine use. More than half of all benzodiazepine users were identified as potential deprescribing candidates (dispensed more than three prescriptions). Women, older patients, multimorbid individuals, and patients with polypharmacy were more likely to use benzodiazepines for a prolonged period. The results show a negative trend of benzodiazepine usage among community-dwelling patients during the pandemic. Community pharmacists can identify potential candidates for deprescribing and initiate a process that ensures more rational use of benzodiazepines and increases the safety of treatment.
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Williams, Hugh, A. Oyefeso, and AH Ghodse. "Benzodiazepine misuse and dependence among opiate addicts in treatment." Irish Journal of Psychological Medicine 13, no. 2 (June 1996): 62–64. http://dx.doi.org/10.1017/s0790966700002445.
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AbstractObjective: Benzodiazepine misuse among opiate addicts is well described but few studies have reported on the occurrence and management of benzodiazepine dependence within this group. This study reports on the nature and extent of benzodiazepine dependence among a group of opiate addicts and describes the patients' treatment progress and requirement for substitute medication.Method: Over a 12 month period routinely collected data on all admissions of opiate addicts to our inpatient treatment and research unit were searched. Specific details were then extracted for those 61 admissions who were opiate dependent and also currently misusing benzodiazepines.Results: 26 (43%) of the 61 admissions were found to bephysically dependent on benzodiazepines. Temazepam and diazepam (respectively) were the most commonly misused preparations and 22% of those using temazepam were injecting it. Patients requiring detoxification were stabilised on doses of diazepam ranging from 20mg to 80mg daily (mean; 40mg). No correlation was found between reported use of benzodiazepines and the dose of diazepam required for stabilisation. Users found to be physically dependent on benzodiazepines more commonly reported daily use and use of two or more benzodiazepines concurrently.Conclusions: Our findings suggest: 1) that benzodiazepine dependence occurs in opiate addicts with a frequency similar to that reported previously for other groups of benzodiazepine users; 2) that individuals using benzodiazepines on a daily basis may be more at risk of developing physical dependence; and 3) that clinically it is difficult to accurately predict requirements for substitute medication solely from patient's reported daily use prior to admission.
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Reid Finlayson, Alistair J., Jane Macoubrie, Christy Huff, D. E. Foster, and Peter R. Martin. "Experiences with benzodiazepine use, tapering, and discontinuation: an Internet survey." Therapeutic Advances in Psychopharmacology 12 (January 2022): 204512532210823. http://dx.doi.org/10.1177/20451253221082386.
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Background: Over 92 million prescriptions for benzodiazepines are dispensed in the United States annually, yet little is known about the experiences of those taking and discontinuing them. Objective: The aim of this study is to assess the experiences of those taking, tapering, or having discontinued benzodiazepines. Methods: An online survey ( n = 1207) elicited information about benzodiazepine use, including long-term use, tapering, discontinuation, and withdrawal symptoms. Results: Symptoms associated with benzodiazepine use, tapering, and discontinuation were numerous and ranged from symptoms such as anxiety, insomnia, and nervousness to digestive problems, irregular heart rhythms, uncontrollable anger, photosensitivity, balance problems, and others. When asked how benzodiazepine symptoms affected their lives, 82.9% reported work problems, 86.3% had problems with social interactions and friendships, and 88.8% had problems with fun, recreation, and hobbies. Suicidal thoughts or attempted suicide was reported by 54.4%, and 46.8% said benzodiazepines caused lost employment. Most of the respondents for whom benzodiazepines were prescribed (76.2%) stated they had not been informed that benzodiazepines were indicated for short-term use only and that discontinuation might be difficult. About a third (31.5%) reported food allergies and/or seasonal allergies that occurred only after benzodiazepine use. Conclusion: The trajectory of those who taper or discontinue benzodiazepines is unpredictable, and many patients experience a range of protracted and severe symptoms, even years after benzodiazepines were completely discontinued. Greater awareness is needed for both prescribers and patients about the potential for a difficult withdrawal from benzodiazepines.
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Warner, A. "Interference of common household chemicals in immunoassay methods for drugs of abuse." Clinical Chemistry 35, no. 4 (April 1, 1989): 648–51. http://dx.doi.org/10.1093/clinchem/35.4.648.
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Abstract I report how some adulterants affect results for drugs of abuse in urine as measured by Roche RIA, Syva emit d.a.u., and Abbott TDx fpia (fluorescence polarization immunoassay) for the following drugs: amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, and phencyclidine (PCP). Sodium chloride interfered negatively with all of these drugs when assayed by emit and caused a slight decrease in measured benzodiazepine concentration by fpia. Drug concentrations were also decreased by added H2O2 (emit: benzodiazepine), Joy detergent (emit: cannabinoid, benzodiazepines, PCP), NaHCO3 (emit: opiate; fpia: PCP), or NaClO [corrected] (emit, RIA, fpia: amphetamines, opiates, PCP; emit, fpia: cannabinoid; emit: benzodiazepines). False-positive results were caused by H2O2 (fpia: benzodiazepines) and Joy (RIA, fpia: benzodiazepine, cannabinoid; fpia: barbiturate, amphetamine). Sodium bicarbonate causes a suspiciously high pH in the urine, NaClO [corrected] an apparently low pH (using pH paper).
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Sim, Faye, Isabel Sweetman, Shitij Kapur, and Maxine X. Patel. "Re-examining the role of benzodiazepines in the treatment of schizophrenia: A systematic review." Journal of Psychopharmacology 29, no. 2 (July 21, 2014): 212–23. http://dx.doi.org/10.1177/0269881114541013.
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Background Benzodiazepine prescribing for schizophrenia occurs in clinical practice and antipsychotic trials. This review examined the clinical outcomes for benzodiazepines in schizophrenia. Method A systematic search identified randomised controlled trials that evaluated benzodiazepines in comparison with placebo or antipsychotics, and also as adjuncts to antipsychotics. Relevant clinical outcome data was extracted. Results Twenty six studies were included with some reporting multiple comparisons. Seven short-term studies compared benzodiazepines with placebo: benzodiazepine superiority was found in two out of five studies for global improvements and two out of four studies for psychiatric/behavioural outcomes. Eleven studies compared benzodiazepines with first-generation antipsychotics (FGAs): four out of nine studies (including two long-term studies) reported greater global improvements for antipsychotics; four out of five studies showed no treatment differences for psychiatric/behavioural outcomes. Fourteen studies compared benzodiazepines (as adjunct to antipsychotics) vs antipsychotics alone (mostly FGAs); benzodiazepine superiority was found for global improvement in one out of eight studies and inferiority in two out of eight short-term studies whereas superiority was found for psychiatric/behavioural outcomes in three out of 12 short-term studies and inferiority in three out of 12 studies. Conclusion Benzodiazepine superiority over placebo was found for global, psychiatric and behavioural outcomes, but inferiority to antipsychotics on longer-term global outcomes. Conflicting evidence exists regarding the addition of benzodiazepines to antipsychotics; thus the use of benzodiazepines in clinical practice and antipsychotic trials should be limited.
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Perkovic-Vukcevic, Natasa, Gordana Vukovic-Ercegovic, Zoran Segrt, Snezana Djordjevic, and Jasmina Jovic-Stosic. "Benzodiazepine poisoning in elderly." Vojnosanitetski pregled 73, no. 3 (2016): 234–38. http://dx.doi.org/10.2298/vsp141208025p.
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Background/Aim. Benzodiazepines are among the most frequently ingested drugs in self-poisonings. Elderly may be at greater risk compared with younger individuals due to impaired metabolism and increased sensitivity to benzodiazepines. The aim of this study was to assess toxicity of benzodiazepines in elderly attempted suicide. Methods. A retrospective study of consecutive presentations to hospital after self-poisoning with benzodiazepines was done. Collected data consisted of patient's characteristics (age, gender), benzodiazepine ingested with its blood concentrations at admission, clinical findings including vital signs and Glasgow coma score, routine blood chemistry, complications of poisoning, details of management, length of hospital stay and outcome. According the age, patients are classified as young (15-40-year old), middle aged (41-65-year old) and elderly (older than 65). Results. During a 2-year observational period 387 patients were admitted because of pure benzodiazepine poisoning. The most frequently ingested drug was bromazepam, the second was diazepam. The incidence of coma was significantly higher, and the length of hospital stay significantly longer in elderly. Respiratory failure and aspiration pneumonia occurred more frequently in old age. Also, flumazenil was more frequently required in the group of elderly patients. Conclusion. Massive benzodiazepines overdose in elderly may be associated with a significant morbidity, including deep coma with aspiration pneumonia, respiratory failure, and even death. Flumazenil is indicated more often to reduce CNS depression and prevent complications of prolonged unconsciousness, but supportive treatment and proper airway management of comatose patients is the mainstay of the treatment of acute benzodiazepine poisoning.
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Schallemberger, Janaína Barden, and Christiane de Fátima Colet. "Assessment of dependence and anxiety among benzodiazepine users in a provincial municipality in Rio Grande do Sul, Brazil." Trends in Psychiatry and Psychotherapy 38, no. 2 (June 27, 2016): 63–70. http://dx.doi.org/10.1590/2237-6089-2015-0041.
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Abstract Introduction: Benzodiazepines are among the most prescribed drugs for anxiety and one of the most used drug classes in the world and have a high potential for addiction. The objective of this study was to assess levels of dependence and anxiety among users of these drugs in the public health system. Methods: This was a cross-sectional, descriptive and quantitative study. Benzodiazepine users treated on the public health system were selected. Anxiety levels were assessed with the Hamilton Anxiety Scale and dependency with the Benzodiazepine Dependence Self-Report Questionnaire. Results: Benzodiazepine use was higher among women and in older age groups. Duration of benzodiazepine use was greater than 1 year for all respondents. The dependence assessment indicated that more than half of users were dependent on taking benzodiazepines and most had a severe degree of anxiety. Conclusion: This study found evidence of prolonged and inappropriate use of benzodiazepines. It is necessary to educate users about the risks of these drugs and to develop strategies to rationalize use of these drugs by working with prescribers and dispensers.
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Keshavan, M. S., P. Moodley, M. Eales, E. Joyce, and V. K. Yeragani. "Delusional Depression following Benzodiazepine Withdrawal." Canadian Journal of Psychiatry 33, no. 7 (October 1988): 626–27. http://dx.doi.org/10.1177/070674378803300709.
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Withdrawal from long-term treatment with benzodiazepines was followed in three patients by a severe delusional depression. The delusional depression may be related to the neurotransmitter changes accompanying benzodiazepine withdrawal. Caution should be exercised in long-term use of benzodiazepines in susceptible individuals.
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Raut, Binod, Anjan Khadka, Pradeep Manandhar, and Kamal Kandel. "Study of association between characteristics of patient and likelihood of benzodiazepine use in psychiatry outpatient department at tertiary care hospital of Kathmandu." Journal of Chitwan Medical College 7, no. 3 (September 30, 2017): 13–20. http://dx.doi.org/10.3126/jcmc.v7i3.23689.
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Introduction: Benzodiazepines exert their pharmacological properties as hypnotics, anxiolytics, anticonvulsants and muscle relaxants. Benzodiazepines are clinically effective for a number of indication including the reduction of anxiety, the induction and maintenance of sleep, muscle relaxation. They have a range of well documented adverse effects that may outweigh the benefits in certain patient population including psychomotor impairment, development of tolerance and dependence, potential for abuse.
Methods: It is a hospital based prospective cross-sectional study conducted in a psychiatry outpatient department of tertiary care hospital. All the patients attended to the outpatient department of psychiatry and prescribed with benzodiazepine were selected for study. Drug therapy details in medication chart review and clinical review in patients treated with benzodiazepines was analyzed to measure the utilization pattern of benzodiazepines in terms of patient characteristics (e.g. age, gender and marital status), occupation, education and diagnosis, number of prescription of benzodiazepines, their doses, frequency, routes of administration and duration of use in each patient.
Results: Out of a total of 384 patients, 246 of the patients had been currently using at least one benzodiazepine. Prevalence of benzodiazepine use was 64%. There was statistically significant association between benzodiazepines use with gender distribution, occupation and education. The prevalence of benzodiazepines use is relatively higher than that reported in the developed countries. Clonazepam was the most widely used benzodiazepine followed by lorazepam.
Conclusion: The study evaluated the association between characteristics of patient and likelihood of benzodiazepines use. This will definitely help to optimize the drug therapy, improve the quality of care and reduce the negative outcomes in the usage of benzodiazepines.
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Carr, Frances, Peter Tian, Jeffrey Chow, Jennifer Guzak, Jean Triscott, Pamela Mathura, Xing Sun, and Bonnie Dobbs. "Deprescribing benzodiazepines among hospitalised older adults: quality improvement initiative." BMJ Open Quality 8, no. 3 (August 2019): e000539. http://dx.doi.org/10.1136/bmjoq-2018-000539.
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Benzodiazepines are recognised as being potentially inappropriate medications for seniors due to their considerable side-effect profile, yet they are commonly prescribed and infrequently discontinued (deprescribed). The study’s primary objective was the deprescription or the dose reduction of benzodiazepines among newly hospitalised seniors using a patient education intervention. A 3-month duration quality improvement study based on the plan–do–study–act model was conducted across two units (3C and 4D) in the Glenrose Rehabilitation Hospital to improve benzodiazepine deprescribing among newly admitted seniors (65 years or older) who were using benzodiazepines. The primary outcome measure was the number of eligible patients who had benzodiazepine deprescribing initiated. A patient education intervention comprising a structured medication review, written patient education (the Eliminating Medications Through Patient Ownership of End Results (EMPOWER) brochure) and at least one brief supportive counselling session by the clinical pharmacist or physician was applied to all eligible patients. All 12 eligible patients consented to benzodiazepine deprescribing; however, only 11 of them (92%) initiated benzodiazepine deprescribing. Six of the 11 patients (55%) had their benzodiazepines discontinued, with the 5 remaining patients (45%) achieving greater than 50% dosage reduction. Seven patients (64%) experienced side effects during the deprescribing process, with over half (57%, n=4) of these seven patients experiencing worsening anxiety symptoms. Five of the 11 patients (45%) required benzodiazepine substitute medications. The use of a structured patient education intervention involving the use of a structured medication review, written patient education material and one-on-one patient counselling can promote benzodiazepine deprescribing. Although worsening anxiety was frequently observed, this was easily managed by the substitution of a more appropriate and clinically indicated medication, which was well tolerated and acceptable by all of our participants. Targeted screening for the presence of anxiety would help to guide the deprescribing process and the need for medication substitution.
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Edinoff, Amber N., Catherine A. Nix, Amira S. Odisho, Caroline P. Babin, Alyssa G. Derouen, Salim C. Lutfallah, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, and Alan D. Kaye. "Novel Designer Benzodiazepines: Comprehensive Review of Evolving Clinical and Adverse Effects." Neurology International 14, no. 3 (August 22, 2022): 648–63. http://dx.doi.org/10.3390/neurolint14030053.
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As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. Meclonazepam ((3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one) is a designer benzodiazepine with additional anti-parasitic effects. Although it has proven to be an efficacious therapy for schistosomiasis, its sedative side effects have prevented it from being marketed as a therapeutic agent. The use of DBZs has been a subject of multiple recent clinical studies, likely related to increasing presence and availability on the internet drug market and lack of regulation. Many studies have aimed to identify the prevalence of DBZs and their effects on those using them. This review discussed these designer benzodiazepines and the dangers and adverse effects that the clinician should know.
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Hammond, Drayton A., Jordan M. Rowe, Adrian Wong, Tessa L. Wiley, Kristen C. Lee, and Sandra L. Kane-Gill. "Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review." Hospital Pharmacy 52, no. 9 (July 17, 2017): 607–16. http://dx.doi.org/10.1177/0018578717720310.
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Purpose: Benzodiazepines are the drug of choice for alcohol withdrawal syndrome (AWS); however, phenobarbital is an alternative agent used with or without concomitant benzodiazepine therapy. In this systematic review, we evaluate patient outcomes with phenobarbital for AWS. Methods: Medline, Cochrane Library, and Scopus were searched from 1950 through February 2017 for controlled trials and observational studies using [“phenobarbital” or “barbiturate”] and [“alcohol withdrawal” or “delirium tremens.”] Risk of bias was assessed using tools recommended by National Heart, Lung, and Blood Institute. Results: From 294 nonduplicative articles, 4 controlled trials and 5 observational studies (n = 720) for AWS of any severity were included. Studies were of good quality (n = 2), fair (n = 4), and poor (n = 3). In 6 studies describing phenobarbital without concomitant benzodiazepine therapy, phenobarbital decreased AWS symptoms ( P < .00001) and displayed similar rates of treatment failure versus comparator therapies (38% vs 29%). A study with 2 cohorts showed similar rates of intensive care unit (ICU) admission (phenobarbital: 16% and 9% vs benzodiazepine: 14%) and hospital length of stay (phenobarbital: 5.85 and 5.30 days vs benzodiazepine: 6.64 days). In 4 studies describing phenobarbital with concomitant benzodiazepine therapy, phenobarbital groups had similar ICU admission rates (8% vs 25%), decreased mechanical ventilation (21.9% vs 47.3%), decreased benzodiazepine requirements by 50% to 90%, and similar ICU and hospital lengths of stay and AWS symptom resolution versus comparator groups. Adverse effects with phenobarbital, including dizziness and drowsiness, rarely occurred. Conclusion: Phenobarbital, with or without concomitant benzodiazepines, may provide similar or improved outcomes when compared with alternative therapies, including benzodiazepines alone.
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Nichols, Taylor A., Sophie Robert, David J. Taber, and Jeffrey Cluver. "Alcohol withdrawal-related outcomes associated with gabapentin use in an inpatient psychiatric facility." Mental Health Clinician 9, no. 1 (January 1, 2019): 1–5. http://dx.doi.org/10.9740/mhc.2019.01.001.
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Abstract Introduction Limited evidence exists evaluating the impact of gabapentin in conjunction with benzodiazepines for the management of alcohol withdrawal. A review of outcomes associated with combination gabapentin and benzodiazepine therapy may illuminate new therapeutic uses in clinical practice. Methods This retrospective study evaluated the impact of gabapentin on as-needed use of benzodiazepines in inpatients being treated for acute alcohol withdrawal. The treatment cohort consisted of patients prescribed gabapentin while on a symptom-triggered alcohol withdrawal protocol. The control cohort consisted of patients on symptom-triggered alcohol withdrawal protocol without concurrent gabapentin use. Secondary objectives included length of hospital stay, duration on alcohol withdrawal protocol, frequency of complicated withdrawal, and use of additionally prescribed as-needed or scheduled benzodiazepines. Results The gabapentin cohort was on the alcohol withdrawal protocol for a similar duration, compared with the control cohort (median of 4 [interquartile range: 2,6] days vs 3 [2,4] days, P = .09, respectively). Similarly, the gabapentin cohort required a median of 1 [1,2] benzodiazepine dose for alcohol withdrawal symptoms compared with a median of 1 [1,2] dose in the control cohort, P = .89. No significant difference was found between cohorts for as-needed and scheduled benzodiazepine use. Length of stay in hospital was similar between groups. Discussion These results suggest that gabapentin use, in conjunction with benzodiazepines, impacts neither the time on alcohol withdrawal protocol or the number of benzodiazepine doses required for withdrawal. Larger, prospective studies are needed to detect if gabapentin alters benzodiazepine usage and to better elucidate gabapentin's role in acute alcohol withdrawal.
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Taylor, S., C. F. M. McCracken, K. C. M. Wilson, and J. R. M. Copeland. "Extent and appropriateness of benzodiazepine use." British Journal of Psychiatry 173, no. 5 (November 1998): 433–38. http://dx.doi.org/10.1192/bjp.173.5.433.
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BackgroundWe sought to determine the extent and appropriateness of benzodiazepine use in an elderly community, by measuring prevalence and incidence of benzodiazepines and examining mental health status as a predictor of benzodiazepine use.MethodData were collected from two longitudinal studies of people from the same community, sampled in 1982–1983 and again in 1989–1991.ResultsBenzodiazepine prevalence did not decrease during the period under study, but there was a significant reduction in anxiolytic use. Prevalence of benzodiazepines in women is twice that in men, and incidence of hypnotics is slightly higher in women. Prevalence and incidence of hypnotics are strongly associated with increasing age. There were high proportions of long-term users (61 and 70%), and continued use was high (52%) among new users. A large proportion of benzodiazepine use was by those who were concurrently depressed. Similarly, anxiety predicted both current and subsequent use of hypnotics.ConclusionsMany older people still use benzodiazepines, contrary to official guidelines with regard to their mental health. Our findings add to the weight of opinion that persistent and long-term use should be discouraged.
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Cook, B., L. Chavez, R. Carmona, and M. Alegria. "Assessing Comorbidities and service use among patients with benzodiazepine abuse." European Psychiatry 33, S1 (March 2016): S294. http://dx.doi.org/10.1016/j.eurpsy.2016.01.1003.
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Prior studies have identified that individuals with comorbid substance use disorder and mental health disorder are at a greater risk of benzodiazepine abuse compared to individuals that present with mental health disorder without an accompanying substance use disorder. These studies were conducted in predominantly white populations, and little is known if the same associations are seen in safety net health care networks. Also, the literature is mixed as to whether or not psychiatrists’ prescription of benzodiazepines places individuals at undue risk of benzodiazepine abuse.We use 2013–2015 electronic health record data from a Boston healthcare system. Patients with benzodiazapene abuse were identified if they had received treatment under the ICD-9 code 304.1. Benzodiazepine abuse was compared between patients with only mental illness and patients with existing comorbid substance and mental health disorder, in unadjusted comparisons and adjusted regression models. Covariates in regression models were used to identify subgroups at higher risk of benzodiazepine abuse.Individuals with benzodiazepine abuse had higher rates of emergency room and inpatient use than patients with other mental health and/or substance use disorders. Those with comorbid substance and mental disorder were significantly more likely than individuals with mental or substance use disorder alone to abuse benzodiazepines (P < .01). Among those with benzodiazepine abuse, 93.3% were diagnosed with a mental illness, 75.6% were diagnosed with a substance use disorder (other than benzodiazepine), and 64.4% had comorbid anxiety disorder and substance use disorder. These analyses suggest that patients with benzodiazepine abuse have complex presentations and intensive service use.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Dowling, M. J., Patrick Doyle, and S. P. Kennelly. "282 A Time to Wean: An Audit on Benzodiazepine and Z-drug Use Amongst Patients Attending a Geriatric Ambulatory Care Day Hospital." Age and Ageing 48, Supplement_3 (September 2019): iii17—iii65. http://dx.doi.org/10.1093/ageing/afz103.177.
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Abstract Background Benzodiazepine prescription is common among the Irish patient cohort. 23% of medical card holders have been prescribed a benzodiazepine or Z-drug, with a third of these being for a period longer than three months. This is despite these drugs being associated with addiction, falls, cognitive and psychomotor impairment, mood disorder, sleep automatism and drug interactions. We performed an audit looking at the repeat prescriptions of patients attending a geriatric day hospital. Methods The repeat prescriptions of all patients currently enrolled at a day hospital were analysed for benzodiazepines or Z-drugs. Medical records were then analysed to look for indication and whether these patients were currently attending psychiatric services. Subsequent to this, notices were placed in the patient consult room in direct line of sight of the registrar reminding them to consider weaning these drugs and detailing the negative side effects and guidelines for weaning from the Canadian National Pain Centre. Results 59 patients were enrolled at the day hospital when the audit was performed. 11 (19%) had either a benzodiazepine or Z-drug as part of their repeat prescription (benzodiazepine-5, Z-drug-5, both-1). The most common benzodiazepines prescribed were diazepam and clonazepam (2 patients on each). Of those prescribed a benzodiazepine, none were currently being weaned. Of those on benzodiazepines, 4 of 6 had a documented psychiatric diagnosis, and 1 of 6 had documented that they were currently attending psychiatric services. A re-audit three months later showed no change in those prescribed benzodiazepines (5/59), and a non-significant increase in those on Z-drugs (9/59, p=0.26). Conclusion This audit showed a significant number of patients attending our day hospital are being prescribed long term benzodiazepines or Z-drugs, and highlights that this setting is an opportune time and place to establish a supported program to wean people off these medications.
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Voica, Donna. "Change in Benzodiazepine Prescribing Practices of Mental Health Providers After Implementation of an Agency-Specific Protocol." Journal of Doctoral Nursing Practice 9, no. 1 (2016): 29–37. http://dx.doi.org/10.1891/2380-9418.9.1.29.
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Purpose: As a class of drugs, benzodiazepines are highly effective in treating anxiety disorders. However, the use of benzodiazepines carries a risk for dependence with an increased incidence in individuals with cooccurring disorders. The project evaluated the impact of a benzodiazepine prescribing protocol on mental health providers’ prescribing practices. Methods: A retrospective chart review (N = 237) was conducted to assess changes in benzodiazepine prescribing patterns prior to and following the implementation of an agency-specific protocol. A convenience sample of 15 providers included nurse practitioners and psychiatrists from a regional mental health center in East Tennessee. For the diagnoses of anxiety disorders, the number of benzodiazepine prescriptions written, dose reduced or discontinued was determined along with concordance to current recommendations for benzodiazepine use. Results: No statistically significant differences were found in scores between study periods, even though there was a decrease in the number of prescriptions written between the pre- (n = 81) and postmeasures (n = 34). Conclusion: The implementation of a benzodiazepine protocol does not necessarily bring about significant changes in providers’ prescribing practices. Audit and feedback are an essential part of the intervention strategy and are often required to change performance-related outcomes.
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Goudarzi, Fazel, Razieh Sadat Mousavi-Roknabadi, Maryam Abdollahpour, and Robab Sadegh. "Hypoglycemia in Patients With Pure Benzodiazepine Poisoning." International Journal of Medical Toxicology and Forensic Medicine 11, no. 2 (June 15, 2021): 32702.1–32702.6. http://dx.doi.org/10.32598/ijmtfm.v11i2.32702.
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Background: Various studies investigated the effects of benzodiazepines on insulin and blood glucose levels and provided contradictory results. The present study aimed to evaluate the clinical effects of benzodiazepine poisoning on hypoglycemia. Methods: This retrospective cross-sectional study (from 22/June/2018 to 22/December/2018) was conducted on all medical records of adult patients with benzodiazepine poisoning who were referred to Ali-Asghar Hospital. The required data were collected using a data-gathering form and then analyzed. Results: In total, 61 patients were enrolled in this study. Furthermore, 19 (31.2%) patients developed hypoglycemia. Besides, 50 (82%) patients used benzodiazepine for a suicide attempt, i.e. higher in patients with hypoglycemia (P<0.0001). Multivariate logistic regression test data indicated that benzodiazepine consumption for suicide attempt (OR=47.978, P=0.001, 95%CI, 5.313-433.277), and the respiratory rate at the time of suicide (OR=0.549, P=0.023, 95%CI, 0.328-0.920) were predictive factors for hypoglycemia in patients with benzodiazepine poisoning. Conclusion: Our study data suggested that 31% of patients who were poisoned with benzodiazepines developed hypoglycemia. The suicidal use of drugs and respiratory rates were predictive factors for hypoglycemia in these patients.
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Paredes, Nivia Pinos, Adriana Inocenti Miasso, and Carlos Renato Tirapelli. "Consumption of benzodiazepines without prescription among first-year nursing students at the University of Guayaquil, school of nursing, Ecuador." Revista Latino-Americana de Enfermagem 16, spe (August 2008): 634–39. http://dx.doi.org/10.1590/s0104-11692008000700021.
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This study aimed to determine the consumption of benzodiazepines without prescription among first-year students from a nursing school of a public University in Ecuador. This is a descriptive, transversal and explanatory study with a quantitative approach. A questionnaire was used for data collection. The population studied was of 181 students. The results showed that 10.5% of the students had consumed benzodiazepine without prescription once in their lives. Of these, 6.1% consumed benzodiazepine in the last year, and 3.9% are currently consuming it. The diazepam was the most consumed BZD without prescription and pharmacies, were the place of higher access. The main reasons for the benzodiazepine consumption were: insomnia, anxiety, stress, depression, family and economical problems. The use of benzodiazepines with non-medicinal purposes is related to problems such as memory loss, retirement syndrome and sedation. When benzodiazepines are consumed jointly with alcohol or other drugs they can lead to coma or death. This study shows the serious consequences benzodiazepines cause when used by nursing students in Ecuador.
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Avallone, R., M. L. Zeneroli, I. Venturini, L. Corsi, P. Schreier, M. Kleinschnitz, C. Ferrarese, et al. "Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy." Gut 42, no. 6 (June 1, 1998): 861–67. http://dx.doi.org/10.1136/gut.42.6.861.
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Background/Aim—Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines.Subjects—Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied.Methods—Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam andN-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay.Results—Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased.Conclusions—Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy.
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Pflanz, Natasha C., Anna W. Daszkowski, Garrett L. Cornelison, James R. Trudell, and S. John Mihic. "An intersubunit electrostatic interaction in the GABAA receptor facilitates its responses to benzodiazepines." Journal of Biological Chemistry 293, no. 21 (April 5, 2018): 8264–74. http://dx.doi.org/10.1074/jbc.ra118.002128.
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Benzodiazepines are positive allosteric modulators of the GABAA receptor (GABAAR), acting at the α–γ subunit interface to enhance GABAAR function. GABA or benzodiazepine binding induces distinct conformational changes in the GABAAR. The molecular rearrangements in the GABAAR following benzodiazepine binding remain to be fully elucidated. Using two molecular models of the GABAAR, we identified electrostatic interactions between specific amino acids at the α–γ subunit interface that were broken by, or formed after, benzodiazepine binding. Using two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes, we investigated these interactions by substituting one or both amino acids of each potential pair. We found that Lys104 in the α1 subunit forms an electrostatic bond with Asp75 of the γ2 subunit after benzodiazepine binding and that this bond stabilizes the positively modified state of the receptor. Substitution of these two residues to cysteine and subsequent covalent linkage between them increased the receptor's sensitivity to low GABA concentrations and decreased its response to benzodiazepines, producing a GABAAR that resembles a benzodiazepine-bound WT GABAAR. Breaking this bond restored sensitivity to GABA to WT levels and increased the receptor's response to benzodiazepines. The α1 Lys104 and γ2 Asp75 interaction did not play a role in ethanol or neurosteroid modulation of GABAAR, suggesting that different modulators induce different conformational changes in the receptor. These findings may help explain the additive or synergistic effects of modulators acting at the GABAAR.
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Fisher, T. E., D. D. Johnson, J. M. Tuchek, and R. D. Crawford. "Evidence for the pharmacological relevance of benzodiazepine receptors to anticonvulsant activity." Canadian Journal of Physiology and Pharmacology 63, no. 11 (November 1, 1985): 1477–79. http://dx.doi.org/10.1139/y85-243.
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Each of a series of benzodiazepines was found to be effective in preventing convulsions evoked by intermittent photic stimulation of epileptic chickens. There was a high correlation between the anticonvulsant potencies (mean effective dosages) and the affinity of the agents for the putative benzodiazepine receptor as measured by displacement of [3H]diazepam from binding sites on chicken synaptosomal membranes. This correlation in a genetic model of epilepsy provides further evidence that benzodiazepines exert their anticonvulsant effects by interacting with the benzodiazepine receptor.
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Apantaku-Olajide, Tunde, Kevin Ducray, Patricia Byrne, and Bobby P. Smyth. "Perception of unmet needs and association with benzodiazepine misuse among patients on a methadone maintenance treatment programme." Psychiatrist 36, no. 5 (May 2012): 169–74. http://dx.doi.org/10.1192/pb.bp.111.036616.
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Aims and methodTo examine patients' perceptions of unmet needs during methadone maintenance treatment (MMT), and to explore the relationship between co-occurring benzodiazepine misuse and severity of needs. A cross-sectional survey was carried out at an MMT programme in Dublin, Ireland. All patients were invited to participate on a voluntary basis. Of the 191 eligible patients, 107 agreed to participate and completed the Camberwell Assessment of Need questionnaire.ResultsUnmet needs for substance misuse treatments, daytime activities, socialisation, money management and psychological distress were high. Fifty-two respondents (49%) reported using non-prescribed benzodiazepines during the past month. Compared with non-users of benzodiazepines, benzodiazepine users reported higher ratings of total and unmet needs (P < 0.05). The number of days using benzodiazepines predicted the severity of needs.Clinical implicationsThe findings highlight the importance of addressing coexisting psychological needs, and further support enhancing treatment interventions for benzodiazepine misuse or dependence among patients on MMT.
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Davies, Simon J. C., Binu Jacob, David Rudoler, Juveria Zaheer, Claire de Oliveira, and Paul Kurdyak. "Benzodiazepine prescription in Ontario residents aged 65 and over: a population-based study from 1998 to 2013." Therapeutic Advances in Psychopharmacology 8, no. 3 (December 5, 2017): 99–114. http://dx.doi.org/10.1177/2045125317743651.
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Background: Although commonly used in anxiety and insomnia, recent guidelines recommend caution when prescribing benzodiazepines in the elderly. Here we examined rates of benzodiazepine prescribing to older adults in Ontario, Canada from 1998 to 2013 and impact of legislation that made prescribing regulations more strict. Method: Annual benzodiazepine prescription rates for Ontario residents aged 65 and over were examined using the Ontario Drug Benefit database which captures all publicly funded prescriptions. Since most drugs, including benzodiazepines, are funded for residents aged ⩾65, data are essentially population-based. Weighted least squares regression methods were used to examine trends in prescribing rates (all benzodiazepines, anxiolytics, hypnotics, short- and long-acting drugs and individual drugs) from 1998 to 2013 for all Ontario residents aged ⩾65 and by sex and 5-year age bands. Impact on monthly prescribing rates of legislative changes (November 2011) which aimed to promote appropriate prescribing and dispensing practices for controlled substances, including requiring prescribers to record specified information, was assessed by constructing an interrupted time-series model. Results: Benzodiazepines were prescribed to 23.2% of the 1,412,638 Ontario residents aged ⩾65 in 1998, declining to 14.9% of 2,057,899 residents aged ⩾65 in 2013 ( p < 0.001 for trend). Rates were significantly greater throughout in older age bands ( p < 0.001) and 1.54–1.62 times greater in females than males ( p < 0.001). Lorazepam was the most prescribed benzodiazepine throughout, but rates declined from 11.4% in 1998 to 8.5% in 2013. Diazepam rates fell from 2.3% to 0.7%. However, clonazepam prescription rates increased until 2011, 1.7-fold overall. After the November 2011 legal changes, downward shifts were observed in total benzodiazepine prescription rates and for each drug individually. The step function, conditional on covariates, suggested benzodiazepine rates after November 2011 were 2.89 per 1000 ( p < 0.001) below rates observed previously, representing a relative reduction of 4.8% compared to the year before the intervention. Conclusion: Benzodiazepine prescribing rates declined markedly in this population from 1998 to 2013. Targeted legislation may have reduced rates, but the effect, although statistically significant, was small.
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Alves-dos-Reis, T., A. L. Papoila, and R. Gusmão. "Changes in prescribing patterns of benzodiazepines after training of general practitioners." European Psychiatry 33, S1 (March 2016): S86. http://dx.doi.org/10.1016/j.eurpsy.2016.01.045.
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IntroductionBenzodiazepines are the most utilized anxiolytic and hypnotic drugs. The high consumption of benzodiazepines has been a concern due to reported side effects of long-term use and dependence. Portugal has the highest benzodiazepine utilization in Europe.ObjectivesTo analyze the change in general practitioners’ (GPs) benzodiazepine prescription pattern after an intervention period.MethodsAn educational session was delivered to a group of intervened GPs. The benzodiazepine prescription pattern of intervened group was compared to the pattern of a non-intervened matched group from the same region, and of another non-intervened matched group from a different region. The research time frame was 12 months before and after intervention. The analysis of the prescription trends used the defined daily dose (DDD) and defined daily dose per 1000 patients per day (DHD) methodology. The statistical methods consisted of segmented regression analysis.ResultsThere was a decrease in benzodiazepine prescription pattern of intervened GPs after intervention (P = 0.005). There was also a decrease in benzodiazepine prescription pattern for the non-intervened group from the same region (P = 0.037) and for the non-intervened group from a different region (P = 0.010). Concerning an analysis by gender, female gender prescribed a higher amount of benzodiazepines. The intervened female gender prescribers presented the highest decrease in prescription trend after intervention (P = 0.008).ConclusionsIntervention was effective in reducing benzodiazepine prescription after intervention. It demonstrates that a single intervention has a positive impact on improving prescription trends. The replication of this intervention might be an opportunity for changing the worrying benzodiazepine utilization in Portugal.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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LINDEN, M., T. BÄR, and B. GEISELMANN. "Patient treatment insistence and medication craving in long-term low-dosage benzodiazepine prescriptions." Psychological Medicine 28, no. 3 (May 1998): 721–29. http://dx.doi.org/10.1017/s0033291798006734.
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Background. Long-term low-dosage dependence on benzodiazepines is traditionally explained by withdrawal symptoms. Previous research has not given much attention to reports that suggest that many patients oppose stopping benzodiazepines long before withdrawal symptoms have developed. This study investigates the scope of and factors associated with this pre-withdrawal treatment insistence.Methods. Patients receiving long-term low-dosage benzodiazepines in primary care were asked to take a drug-holiday of at least 3 weeks. Sociodemographic, medication, morbidity and attitudinal variables were assessed in addition to the GPs' perceptions of their patients.Results. Two-thirds of the patients rejected the drug-holiday proposal. Patients who refused a drug-holiday were less educated and were using a higher percentage of long-acting benzodiazepines than patients who accepted the drug-holiday proposal. Those who refused were seen by their GPs as being more complaining, harder to satisfy and less co-operative.Conclusions. These results provide evidence for drug-seeking or craving behaviour of patients who receive low-dosage benzodiazepine prescriptions. A major problem in benzodiazepine withdrawal occurs before the withdrawal programme has even begun. These data show that benzodiazepine low-dosage dependence should be considered a real form of dependence.
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Chatterjee, Devoshree, Steve Iliffe, Kalpa Kharicha, Danielle Harari, Cameron Swift, Gerhard Gillman, and Andreas E. Stuck. "Health risk appraisal in older people 7: long-acting benzodiazepine use in community-dwelling older adults in London: is it related to physical or psychological factors?" Primary Health Care Research & Development 18, no. 03 (February 22, 2017): 253–60. http://dx.doi.org/10.1017/s1463423617000068.
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Aim To investigate whether the use of long-acting benzodiazepines, in individuals aged 65 and over is mediated by physical or psychological factors. Background Long-acting benzodiazepine consumption among older people has implications for mortality, morbidity and cost-effective prescribing. Two models explain benzodiazepine use in this age group, one linked to physical illness and disability and one to psychological factors. Methods Secondary analysis of baseline data from a study of 1059 community-dwelling non-disabled people aged 65 years and over recruited from three general practices in London. For this analysis, use of long-acting benzodiazepines was defined as any self-reported use of diazepam or nitrazepam in the last four weeks. Associations between demographic factors, health service use, and physical and psychological characteristics and benzodiazepine use were investigated. Findings The prevalence of benzodiazepine use in this sample was 3.3% (35/1059). In univariate analyses, benzodiazepine use was associated with female gender, low income, high consultation rates, physical factors (medication for arthritis or joint pain, polypharmacy, difficulties in instrumental activities of daily living, recent pain) and psychological factors (poor self-perceived health, social isolation, and symptoms of anxiety or agitation). In a multivariate logistic regression analysis only two factors retained statistically significant independent associations with benzodiazepine use: receiving only the state pension (OR=4.0, 95% CI: 1.70, 9.80) and pain in the past four weeks (OR=3.79, 95% CI: 1.36, 10.54).
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Rowntree, R., J. Sweeney, N. Crumlish, and G. Flynn. "How do we compare with best practice? A completed audit of benzodiazepine and z-hypnotic prescribing." Irish Journal of Psychological Medicine 35, no. 4 (June 23, 2016): 321–24. http://dx.doi.org/10.1017/ipm.2016.24.
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ObjectivesTo compare benzodiazepine and z-hypnotic prescribing practices in an inpatient psychiatric unit to best practice standards.MethodsMedication charts of all inpatients in the psychiatric unit, over a 1-week period, were reviewed. Details of current benzodiazepine and z-hypnotic prescriptions were collected. Information collected included the substance prescribed, duration and administration instructions. Feedback was communicated to medical practitioners through a presentation and email. A re-audit was completed 4 months later.ResultsThere were increases in total benzodiazepine and z-hypnotic prescribing despite intervention. A reduction of 2 mg occurred in the mean regular dose of benzodiazepine prescribed. Lorazepam was the most prescribed benzodiazepine throughout. In both data sets, at least 50% of regular z-hypnotics and benzodiazepines were initiated before admission. There was an increase of 14% in regular benzodiazepines initiated in hospital exceeding 4 weeks in duration. In neither data collection did regular z-hypnotics initiated in hospital exceed this cut off. A greater number of individuals were in the process of being withdrawn from regular benzodiazepine or z-hypnotic prescriptions in the re-audit. There were minimal improvements in ‘as required’ prescribing as regards documentation of an indication, time limit and maximum dose.ConclusionThe increase in overall prescribing, despite intervention, maybe because these medications continued to be indicated in the acute presentations needing inpatient treatment. The small improvements in ‘as required’ prescribing patterns suggest that the intervention was limited in effecting change in this area.
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Bobes, J., G. Rubio, A. Terán, G. Cervera, V. López-Gómez, I. Vilardaga, and M. Pérez. "Pregabalin for the discontinuation of long-term benzodiazepines use: An assessment of its effectiveness in daily clinical practice." European Psychiatry 27, no. 4 (May 2012): 301–7. http://dx.doi.org/10.1016/j.eurpsy.2010.12.004.
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AbstractPurposeTo evaluate the effectiveness and tolerability of pregabalin in the management of the discontinuation of benzodiazepines in long-term users.Subjects and methodsWe performed a 12-week, prospective, uncontrolled, non-interventional, and observational study in patients aged 18 years old or above, who met DSM-IV-TR criteria for benzodiazepine dependence without other major psychiatry disorder. Evaluations included the Benzodiazepine Withdrawal Symptom Questionnaire, the Hamilton Anxiety Rating Scale, the Clinical Global Impression Scale, and the Sheehan Disability Scale. A urine drug screen for benzodiazepines was performed at baseline and every 4 weeks thereafter. The primary effectiveness variable was success rate, defined as achievement of benzodiazepine-free status at week 12 according to the urine drug screen.Results and discussionThe mean dose at week 12 was 315 (±166) mg/day. The success rate of the benzodiazepine taper in the primary efficacy population (n = 282) was 52% (95% confidence interval [CI], 46–58). Success rates for women and men were 58% (95% CI, 49–67) and 46% (95% CI, 38–55), respectively. The success rates did not differ according to either the benzodiazepine of abuse or the presence of other substance use disorders. Significant and clinically relevant improvements were observed in withdrawal and anxiety symptoms, as well as in patients’ functioning. At week 12, tolerability was rated as good or excellent by 90% and 83% of the clinicians and patients, respectively.ConclusionOur results suggest that pregabalin is an efficacious and well-tolerated adjunctive treatment for benzodiazepine withdrawal.
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Teuber, L., F. Watjen, and L. H. Jensen. "Ligands for the Benzodiazepine Binding Site - a Survey." Current Pharmaceutical Design 5, no. 5 (May 1999): 317–43. http://dx.doi.org/10.2174/138161280505230110100242.
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Abstract: y-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian Central Nervous System (CNS). GABA participates in the 1·egulation of neuronal excitability through interaction with specific membrane proteins (the GABAA receptors). The binding of GABA to these postsynaptic receptors, results in an opening of a chloride channel integrated in the receptor which allows the entry of c1- and consequently leads to hyperpolarization of the recipient cell. The action of GABA is allosterically modulated by a wide variety of chemical entities which interact with distinct binding sites at the GABAA receptor complex. One of the most thoroughly investigated rnodulatory site is the benzodiazepin binding site. The benzodiazepines constitute a well-known class of therapeutics displaying hypnotic, anxiolytic and anticonvulsant effects. Their usefulness, however, is limited by a broad range of side effects comprising sedation, ataxia, amnesia, alcohol and barbiturate potentiation, tolerance development and abuse potential. Consequently, there has been an intensive search for modulatory agents with an improved profile, and a diversity of chemical entities distinct from the benzodiazepines. but with GABA modulatory effects have been identified. The existence of endogenous ligands for the GABAA receptor complex beside GABA has often been described, but their role in the regulation of GABA action is still a matter of controversy. The progress of molecular biology during the last decade has contributed enormously to the understanding of benzodiazepine receptor pharmacology. A total of 14 GABAA receptor subunits have been cloned from mammalian brain and have been expressed/co-expressed in stable cell lines. These transfected cells constitute an important tool in the characterization of subtype selective ligands. In spite of the rapidly expanding knowledge of the molecular and pharmacological mechanisms involved in GABA/benzodiazepine related CNS disorders. the identification of clinically selective acting drugs is still to come.
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Gould, Rebecca L., Mark C. Coulson, Natasha Patel, Elizabeth Highton-Williamson, and Robert J. Howard. "Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials." British Journal of Psychiatry 204, no. 2 (February 2014): 98–107. http://dx.doi.org/10.1192/bjp.bp.113.126003.
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BackgroundThe use of benzodiazepines has been advised against in older people, but prevalence rates remain high.AimsTo review the evidence for interventions aimed at reducing benzodiazepine use in older people.MethodWe conducted a systematic review, assessment of risk of bias and meta-analyses of randomised controlled trials of benzodiazepine withdrawal and prescribing interventions.ResultsTen withdrawal and eight prescribing studies met the inclusion criteria. At post-intervention, significantly higher odds of not using benzodiazepines were found with supervised withdrawal with psychotherapy (odds ratio (OR) = 5.06, 95% CI 2.68–9.57,P<0.00001) and withdrawal with prescribing interventions (OR = 1.43, 95% CI 1.02–2.02,P=0.04) in comparison with the control interventions treatment as usual (TAU), education placebo, withdrawal with or without drug placebo, or psychotherapy alone. Significantly higher odds of not using benzodiazepines were also found for multifaceted prescribing interventions (OR = 1.37, 95% CI 1.10–1.72,P= 0.006) in comparison with control interventions (TAU and prescribing placebo).ConclusionsSupervised benzodiazepine withdrawal augmented with psychotherapy should be considered in older people, although pragmatic reasons may necessitate consideration of other strategies such as medication review.
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Vejdělek, Zdeněk, Jan Metyš, Jiří Holubek, Miloš Buděšínský, Emil Svátek, Oluše Matoušová, and Miroslav Protiva. "Potentional anxiolytics and hypnotics: 1-(Alkanesulfonamidoalkyl)-6-aryl-8-halogeno-s-triazolo[4,3-a]-1,4-benzodiazepines and related compounds." Collection of Czechoslovak Chemical Communications 53, no. 1 (1988): 132–44. http://dx.doi.org/10.1135/cccc19880132.
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7-Chloro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-thione and its 5-(2-chlorophenyl) and 7-bromo-5-(2-chlorophenyl)analogues were reacted with N-(methanesulfonyl)- and N-(ethanesulfonyl)glycine and –alanine hydrazides (X-XIII) in boiling butanol to give the title compounds Iabc - IVabc. The alanine-derived substances IIIabc and IVabc were characterized by 1H NMR spectra as mixtures of two diastereoisomers. Similar reactions of 5-methylimidazole-4-carboxylic acid hydrazide (XIV) gave the s-triazolo[4,3-a]-1,4-benzodiazepines Vabc together with their ring-opened precursors XVI and XVII. The compounds prepared showed the activity profile of the anxiolytic and hypnotic 4H-s-triazolo[4,3-a]-1,4-benzodiazepine derivatives.
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Fortin, Dany, Michel Préville, Claire Ducharme, Réjean Hébert, Jacques Allard, Jean-Pierre Grégoire, Lise Trottier, and Anick Bérard. "Facteurs associés à la consommation de courte et de longue durée des benzodiazépines chez les personnes âgées du Québec." Canadian Journal on Aging / La Revue canadienne du vieillissement 24, no. 2 (2005): 103–13. http://dx.doi.org/10.1353/cja.2005.0062.
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ABSTRACTIn Quebec, benzodiazepines are some of the most extensively used drugs by the elderly. The goal of this study was to identify factors associated with short- and long-term benzodiazepine use among 2,039 elderly persons having participated in the Quebec Health Survey conducted in 1998. Results of the multivariate, multinomial logistic regression showed that a higher number of chronic health problems, a higher number of physicians visited and general practitioners consulted were associated with short- and long-term use of benzodiazepines. Factors specifically associated with long-term use were female gender (OR=1.84) and the presence of benzodiazepine users in the household (OR=1.90). In this study, we were unable to show a difference between the two groups of users with regards to the risk factors studied. This result leads us to conclude that prevention of long-term use must be aimed at all new benzodiazepine users.
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Grande, G., I. Tramacere, D. L. Vetrano, S. Pomati, C. Mariani, and G. Filippini. "Use of benzodiazepines and cognitive performance in primary care patients with first cognitive complaints." International Psychogeriatrics 30, no. 4 (November 10, 2017): 597–601. http://dx.doi.org/10.1017/s104161021700223x.
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ABSTRACTThe aim of the present study is to investigate the impact of benzodiazepine use on cognitive performance in primary care patients with first cognitive complaints. The association between the exposition to benzodiazepines (short and long half-life) and cognitive performance, evaluated through the Mini Mental State Examination (MMSE), was tested through analysis of the covariance and logistic regression models. Within the 4,249 participants (mean age 77.0 ± 8.2, 66.4% women), 732 (17%) were on benzodiazepines. When compared with non-users, short- and long-acting benzodiazepine users presented overlapping adjusted MMSE mean scores (respectively, mean MMSE score: 25.3, 95%CI 25.2–25.5; 25.4, 95%CI 25.1–25.7, and 25.9, 95%CI 25.3–26.4; p = 0.156). When tested according to the logistical regression model, after adjusting for potential confounders, no association was found between short and long acting benzodiazepine use and a MMSE < 24 (respectively, OR 0.9, 95%CI 0.7–1.2; OR 0.8, 95%CI 0.7–1.3) as compared with non-users. In conclusion, according to the results of our study, benzodiazepine use seems not to impact on cognitive performance- as assessed with the MMSE- of primary care patients referring to GPs for first cognitive complaints.
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Soyka, Michael. "Missbrauch und Abhängigkeit von Benzodiazepinen und Z-Drugs." Nervenheilkunde 40, no. 08 (July 2021): 636–47. http://dx.doi.org/10.1055/a-1523-5718.
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ZUSAMMENFASSUNGMissbrauch und Abhängigkeit von Sedativa und Hypnotika sind klinisch häufig (Prävalenz ca. 2%), insbesondere von Benzodiazepinen und Non-Benzodiazepin-Hypnotika (Z-Drugs). Beide Substanzgruppen haben ältere und weit toxischere Sedativa und Hypnotika wie Barbiturate und Meprobamat zu Recht verdrängt. Benzodiazepine wie Z-Drugs entfalten ihre Wirkung über den inhibitorischen GABA-Rezeptor und können beide eine erhebliche Toleranz induzieren, was klinisch zu Dosissteigerungen, physischer und psychischer Abhängigkeit, Kontrollverlust sowie Entzugssymptomen führen kann. Prädisponierende Faktoren sind neben dem Geschlecht, Frauen sind häufiger betroffen, vor allem psychiatrische und psychosomatische Erkrankungen, insbesondere Angst und Schlafstörungen, aber auch psychosomatische Störungen und chronische Schmerzerkrankungen. Besonders häufig und lange werden Benzodiazepine älteren Patienten verschrieben, entgegen aller Leitlinienempfehlungen.Therapeutisch gesichert ist, dass bei Benzodiazepinabhängig-keit ein langsames Ausschleichen über viele Wochen, manchmal sogar Monate notwendig ist. Ansonsten können erhebliche Entzugserscheinungen inklusive epileptischen Anfällen, Psychosen und Delire auftreten. Das Entzugssyndrom bei Sedativa und Hypnotika ist sehr vielgestaltig mit Depression, Agitation, innerer Unruhe und Perzeptions-und Schlafstörungen als häufigen Symptomen. Die übrige Therapie ist pragmatisch und richtet sich nach den zugrunde liegenden psychischen Störungen und Entzugssymptomen. Im Wesentlichen werden Antidepressiva eingesetzt. Kurzzeitinterventionen werden empfohlen. Psychotherapeutisch haben sich Psychoedukation, kognitive Verhaltenstherapie oder motivationale Therapien bewährt.
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Huff, Christy, A. J. Reid Finlayson, D. E. Foster, and Peter R. Martin. "Enduring neurological sequelae of benzodiazepine use: an Internet survey." Therapeutic Advances in Psychopharmacology 13 (January 2023): 204512532211455. http://dx.doi.org/10.1177/20451253221145561.
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Introduction: Benzodiazepine tapering and cessation has been associated with diverse symptom constellations of varying duration. Although described in the literature decades ago, the mechanistic underpinnings of enduring symptoms that can last months or years have not yet been elucidated. Objective: This secondary analysis of the results from an Internet survey sought to better understand the acute and protracted withdrawal symptoms associated with benzodiazepine use and discontinuation. Methods: An online survey ( n = 1207) was used to gather information about benzodiazepine use, including withdrawal syndrome and protracted symptoms. Results: The mean number of withdrawal symptoms reported by a respondent in this survey was 15 out of 23 symptoms. Six percent of respondents reported having all 23 listed symptoms. A cluster of least-frequently reported symptoms (whole-body trembling, hallucinations, seizures) were also the symptoms most frequently reported as lasting only days or weeks, that is, short-duration symptoms. Symptoms of nervousness/anxiety/fear, sleep disturbances, low energy, and difficulty focusing/distractedness were experienced by the majority of respondents (⩾85%) and, along with memory loss, were the symptoms of longest duration. Prolonged symptoms of anxiety and insomnia occurred in many who have discontinued benzodiazepines, including over 50% who were not originally prescribed benzodiazepines for that indication. It remains unclear if these symptoms might be caused by neuroadaptive and/or neurotoxic changes induced by benzodiazepine exposure. In this way, benzodiazepine withdrawal may have acute and long-term symptoms attributable to different underlying mechanisms, which is the case with alcohol withdrawal. Conclusions: These findings tentatively support the notion that symptoms which are acute but transient during benzodiazepine tapering and discontinuation may be distinct in their nature and duration from the enduring symptoms experienced by many benzodiazepine users.
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Hawley, C. J., M. Tattersall, C. Dellaportas, and C. Hallstrom. "Comparison of Long-Term Benzodiazepine Users in Three Settings." British Journal of Psychiatry 165, no. 6 (December 1994): 792–96. http://dx.doi.org/10.1192/bjp.165.6.792.
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BackgroundMost studies of chronic benzodiazepine users consider selected populations which may be unrepresentative. This study was undertaken to examine possible differences between groups.MethodSubjects chosen were benzodiazepine users in general practice, a hospital clinic, and attending TRANX trials. Descriptive data were collected on characteristics and outcome.ResultsRANX trial patients had the best outcome (P = 0.027). Hospital cases used high doses of anxiolytic benzodiazepines; concomitant mental disorder, including schizophrenia, was common. General practice cases were older and mainly used hypnotics (P < 0.05).ConclusionsBecause groups of benzodiazepine users are different, there cannot be one single management approach. Cases require individual medical assessment.
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Boulter, Jason H., Brian P. Curry, Nicholas S. Szuflita, Charles A. Miller, Joseph Spinelli, John J. Delaney, Chris J. Neal, Christopher J. Spevak, and Randy S. Bell. "Protocolization of Post-Transforaminal Lumbar Interbody Fusion Pain Control with Elimination of Benzodiazepines and Long-Acting Opioids." Neurosurgery 86, no. 5 (July 5, 2019): 717–23. http://dx.doi.org/10.1093/neuros/nyz232.
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Abstract BACKGROUND The opioid epidemic continues to worsen with a concomitant increase in opioid-related mortality. In response, the Department of Defense and Veterans Health Agency recommended against the use of long-acting opioids (LAOs) and concurrent use of opioids with benzodiazepines. Subsequently, we eliminated benzodiazepines and LAOs from our postoperative pain control regimen. OBJECTIVE To evaluate the impact of removing benzodiazepines and LAOs on postoperative pain in single-level transforaminal lumbar interbody fusion (TLIF) patients. METHODS A retrospective cohort study of single-level TLIF patients from February 2016-March 2018 was performed. Postoperative pain control in the + benzodiazepine cohort included scheduled diazepam with or without LAOs. These medications were replaced with nonbenzodiazepine, opioid-sparing adjuncts in the −benzodiazepine cohort. Pain scores, length of hospitalization, trigger medication use, and opioid use and duration were compared. RESULTS Among 77 patients, there was no difference between inpatient pain scores, but the -benzodiazepine cohort experienced a faster rate of morphine equivalent reduction (−18.7%, 95% CI [−1.22%, −36.10%]), used less trigger medications (−1.55, 95% CI [−0.43, −2.67]), and discharged earlier (0.6 d; 95% CI [0.01, 1.11 d]). As outpatients, the −benzodiazepine cohort was less likely to receive opioid refills at 2 wk (29.2% vs 55.8%, P = .021) and 6 mo postoperatively (0% vs 13.2%, P = .039), and was less likely to be using opioids by 3 mo postoperatively (13.3% vs 34.2%, P = .048). CONCLUSION Replacement of benzodiazepines and LAOs in the pain control regimen for single-level TLIFs did not affect pain scores and was associated with decreased opioid use, a reduction in trigger medications, and shorter hospitalizations.