Prolonged Use Of Benzodiazepines Research Articles

Consequences of prolonged use of benzodiazepines related to the increase in mental disorders: a literature review

Consequences of prolonged use of benzodiazepines related to the increase in mental disorders: a literature review

The Use of Benzodiazepines Among Brazilian Women: An Integrative Literature Review

The prolonged use of benzodiazepines among women has been a recurring issue in health services. Hence, this study aimed to conduct an integrative literature review to identify the profile of Brazilian women regularly using benzodiazepines. The SciELO, PePSIC, and BVS-LILACS databases were searched, and 86 articles were identified by combining the keywords “mulher(es) AND benzodiazepínico(s)”, but only 11 papers met the inclusion criteria. Data revealed a higher concentration of women aged between 40 and 60 years old who used benzodiazepines for between one month and 37 years to treat insomnia, anxiety, headaches, and sadness. Benzodiazepines appear as a resource to escape problems and are usually prescribed by general practitioners without taking into account these women’s social issues that involve role overload, among other factors.

Profile of benzodiazepine users attending primary healthcare services in the city of Chapecó, Santa Catarina, Brazil

Primary Health Care is a transversal point in the Psychosocial Care Network, responsible for attending to demands related to mental suffering. Although medication represents the main treatment option, the prolonged use of benzodiazepines may lead to tolerance and consequent dependence. The objective of this study is to analyze the frequency and characteristics of benzodiazepine users attending primary healthcare services, through a cross-sectional study conducted in Chapecó, Santa Catarina, a municipality in southern Brazil. Higher proportional prescription was observed in adult and elderly women, with predominance among individuals who were women (80%), white (67.9%), and married (50.7%), with a median age of 56 years. These findings suggest a need to plan and implement changes in the procedures for prescribing and administering benzodiazepines.

Protocolized Sedative Weaning vs Usual Care in Pediatric Critically Ill Patients: A Pilot Randomized Controlled Trial.

ABSTRACTAimsThe prolonged use of benzodiazepines and opioids can lead to an increase in the incidence of withdrawal syndrome. One of the known risk factors is the lack of a sedative-weaning protocol. This study established a sedative-weaning protocol and compared this protocol with the usual care of weaning in high-risk critically ill children.Materials and methodsThis was an open-label, randomized controlled trial in a tertiary-care hospital. We recruited children aged 1 month to 18 years who had received intravenous sedative or analgesic drugs for at least 5 days. The exclusion criteria were patients who had already experienced the withdrawal syndrome. We established a weaning protocol. Eligible patients were randomly divided into the protocolized (intervention) and usual care (control) groups. The primary objective was to determine the prevalence of the withdrawal syndrome compared between two groups.ResultsThirty eligible patients were enrolled (19 in the intervention and 11 in the control group). Baseline characteristics were not significantly different between both the groups. The prevalence of the withdrawal syndrome was 84% and 81% of patients in the intervention and control group, respectively. The duration of the initial weaning phase was shorter in the intervention group than in the control group (p value = 0.026). The cumulative dose of morphine solution for rescue therapy in the intervention group was statistically lower than that in the control group (p value = 0.016).ConclusionThe implementation of the sedative-weaning protocol led to a significant reduction in the percentage of withdrawal days and length of intensive care unit stay without any adverse drug reactions. External validation would be needed to validate this protocol.ClinicalTrials.gov identifierNCT03018977How to cite this articleTiacharoen D, Lertbunrian R, Veawpanich J, Suppalarkbunlue N, Anantasit N. Protocolized Sedative Weaning vs Usual Care in Pediatric Critically Ill Patients: A Pilot Randomized Controlled Trial. Indian J Crit Care Med 2020;24(6):451–458.

Tapering Recommendations for Benzodiazepines

Tapering Recommendations for Benzodiazepines

Treatment of Anxiety Disorders - The Role of Pharmacists

Abstract Anxiety disorders represent the group of the most prevalent mental diseases which may have serious negative consequences for mental and social health. Anxiety is generally treated with a combination of the psychotherapeutic treatment and pharmacotherapy. Pharmacotherapy of anxiety implies the use of antidepressants, which are used as basic drugs, and an additional therapy with anxiolytics. This therapeutic approach in the treatment of anxiety disorders is accompanied by significant limitations. Adherence of anxiety patients is often insufficient due to the late onset of the effects of antidepressants, the appearance of adverse effects, the stigmatization of psychiatric patients in society and other reasons. Certain exogenous factors, such as an excessive use of coffee, smoking of marijuana, sleep disorders and personal problems, such as family problems or financial problems, can exacerbate anxiety and make it more difficult to treat it. Prolonged use of benzodiazepines, as an adjunct therapy in the treatment of anxiety, may be accompanied by the development of psycho-physical dependence. Finally, the drugs used to treat anxiety have a serious potential for the drug-drug interactions. All of these limitations may be completely or partially overcome through the active participation of Pharmacists as equal members of collaborative medical teams for the treatment of anxiety disorders.

Polypharmacy and potentially inappropriate medication use in older patients with multiple myeloma, related to fall risk and autonomous neuropathy.

Multiple myeloma is a chronic, uncurable hematological cancer with the involvement of multiple organ systems. As a disease affecting older patients, the treatment of multiple myeloma should be based on individual patient characteristics. Polypharmacy is an increasing problem in the care of older patients and in patients with multiple myeloma, polypharmacy is almost inevitable. We aimed to evaluate the applicability of polypharmacy definitions and the relation of polypharmacy with disease outcomes in patients with multiple myeloma. Eighty patients older than 65 years and diagnosed with multiple myeloma were retrospectively enrolled. Patient files, prescriptions, evaluations for polypharmacy were determined according to Beers and START/STOPP criteria. Outcomes were recorded from files in terms of fractures, autonomous neuropathy, and renal functions. Polypharmacy with ≥4 drugs was observed in 65 patients while polypharmacy with ≥5 drugs was observed in 51 patients. Autonomous neuropathy, polypharmacy with more than four or five medications, and use of multiple medications in the same category were related with poor ECOG performance status in women, while prolonged use of benzodiazepines and central nervous system (CNS) affecting drugs and inappropriate polypharmacy were more frequent in men with poor ECOG performance status. The majority of patients aged 75-84 years were observed to use inappropriate polypharmacy. Autonomous neuropathy and fall risk were observed to be significantly related with inappropriate polypharmacy. Drugs affecting balance and perception should be reconsidered in patients with multiple myeloma.

Long-term benzodiazepine use in patients taking antidepressants in a public health setting in Brazil: a cross-sectional study

ObjectiveThe aims of the study were to investigate the prevalence of long-term use of benzodiazepines in patients taking antidepressants and to identify the risk factors associated with the prolonged use...

Use of Benzodiazepines and Hypnotic Medications in Psychiatry Older Adult Outpatients

Benzodiazepines have anxiolytic, hypnotic, anticonvulsant, and muscle-relaxing properties, therefore, a widely prescribed treatment for anxiety and insomnia. They bind to gamma-aminobutyric acid type A (GABAA) receptors, which are responsible for most of the inhibitory neurotransmission in the central nervous system and these receptors are a major target of alcohol, barbiturates, muscle relaxants, and other medications with sedative effects, resulting in tolerance and dependence [1]. Benzodiazepines are categorized into short (15 to 30 minutes), intermediate (30 to 60 minutes), and long-acting agents (one hour or longer). Benzodiazepines are frequently prescribed for elderly patients living in the community and for those in hospitals and institutions. Prolonged use of benzodiazepines is particularly likely in old age for the treatment not only of insomnia and anxiety, but also of a wide range of nonspecific symptoms. Long term users are likely to have multiple concomitant physical and psychological health problems [2]. Benzodiazepines produce dependence, reduce attention, memory, and motor ability. They can cause disinhibition or aggressive behavior, facilitate the appearance of delirium, and increase accident and mortality rates in people older than 60 [3]. According to Maudsley guidelines, benzodiazepines use in elderly are poorly supported for their link to cognitive decline, increase risk of falls and hip fractures [4]. And, if indicated, short acting agents should be avoided. Long acting agents should be started in low doses and patients need to be followed and reassessed regularly. Zolpidem or melatonin are indicated for insomnia, clonazepam and diazepam for agitation and pregabalin for generalized anxiety disorder [5].

Psychotropic Drugs Associated With Increased Risk for Falls

Results from a retrospective observational study conducted in the Netherlands show that patients who are prescribed psychotropic drugs are at a significantly increased risk for falls. Taking psychotropic drugs on a scheduled basis was associated with an almost threefold increase in the incidence of falls. Researchers found that the risk was increased for both antipsychotics and antidepressants (J Am Med Dir Assoc 2016;17:1089–93). Psychotropic drugs (taken only on an as-needed basis) and benzodiazepines were associated with an increased risk of falls as well, although these associations did not reach statistical significance. Researchers also found that a combination of two or three of these drug classes was associated with increased risk. Researchers evaluated 2,368 nursing home residents at nine locations in Eindhoven, the Netherlands, for a total of 538,575 person-days. The mean age of the study participants was 83.9 years, and the mean follow-up period was 506 days. All residents who stayed at one of the locations for at least 1 day from May 2012 through April 2014 were included, but residents in palliative units were excluded. The mean number of psychotropic drug prescriptions per person-day was 1.2. A total of 1,629 patients (68.8%) were prescribed at least one psychotropic drug per day during a total of 318,128 person-days (59.1%). Scheduled prescriptions with or without an as-needed prescription were assigned on a total of 270,781 person-days (50.3%). Only prescriptions on an as-needed basis were assigned on 47,347 person-days (8.8%). Benzodiazepines were the most commonly prescribed class of drug. A total of 794 residents (33.5%) experienced at least one fall on 2,453 person-days (0.5%), for a fall incidence of 1.7 falls per person-year. Most falls occurred on days when a psychotropic drug was prescribed on a scheduled basis, with or without an as-needed prescription (1,652 person-days, 0.6%). At least one fall per person-day occurred on 175 person-days (0.4%) when a drug was prescribed on an as-needed basis only. At least one fall per person-day occurred on 618 person-days (0.3%) on days when no psychotropic drugs were prescribed. By percentage of person-days, falls were most likely to occur in patients taking antipsychotics (Table 1). Source: J Am Med Dir Assoc 2016;17:1089–93. “In subgroup analysis, only the prescription of benzodiazepines on a scheduled basis showed no statistical significant association,” the researchers wrote. “A hypothesis for this finding could be the fact that prolonged use of benzodiazepines results in adaptation of benzodiazepine receptors and could lead to habituation. For that reason, fall incidence could be lower while using a benzodiazepine on a scheduled basis as compared to incidental use.” The researchers also noted that fall risk was much higher for men. “Our finding that males were 87% more at risk of falling could possibly be explained by the higher prevalence of antipsychotic and antidepressant prescriptions among the male residents of our study population. However, it is also possible that our male residents had a diversity of comorbidities that influenced fall risk.” Jason Harris is a freelance writer based in Philadelphia.

Uso de benzodiazepínicos entre idosos: o alívio de "jogar água no fogo", não pensar e dormir

OBJETIVO: Compreender a percepção e os significados que os idosos atribuem a suas experiências relacionadas ao uso prolongado de benzodiazepínicos. MÉTODOS: Trabalho de abordagem qualitativa, de cunho antropológico, realizado junto a idosos participantes do Projeto Bambuí, estudo de base populacional sobre as condições de saúde da população idosa, realizado na cidade de Bambuí-MG. Foram realizadas entrevistas semiestruturadas com 22 idosos, sem comprometimento cognitivo e residentes na cidade de Bambuí-MG, que relataram uso de medicação benzodiazepínica. RESULTADOS: No grupo pesquisado, o uso de benzodiazepínicos foi compatível com a definição de "padrão de uso crônico", variando de seis meses a 40 anos, sendo o medicamento mais utilizado o Clonazepam. A coleta e análise dos dados foram guiadas pelo modelo de signos, significados e ações. Emergiram como categorias: a utilização de um remédio "muito bom"; o remédio bom que "parece que vicia"; a (des)obediência à prescrição médica; e o alívio. CONCLUSÃO: Os idosos entrevistados justificam o uso crônico de benzodiazepínicos como um paliativo para lidar com dificuldades existenciais decorrentes de situações culturais, sociais e familiares, as quais precisam ser abordadas nos serviços de saúde.

Prolonged Use of Benzodiazepines for Sleep Disturbances in the Elderly: Quality of Sleep and Related Comorbidities

Prolonged Use of Benzodiazepines for Sleep Disturbances in the Elderly: Quality of Sleep and Related Comorbidities

Prescripción inadecuada en pacientes polimedicados mayores de 64 años en atención primaria

ObjectiveTo describe inappropriate prescribing (IP) in the polymedicated population over 64 years-old in primary care using the STOPP/START criteria. DesignThe study design was descriptive, cross-sectional and multicenter. LocationFour urban primary care centers in Barcelona.Participants Patients over 64years-old with more than 5 prescribed drugs for at least 6months (n=467).Main measurements Major health problems, chronically prescribed drugs, and percentage of IP using the STOPP/START criteria were studied. Percentage of IP considered as the percentage of patients with at least one STOPP or START non-compliance criterion was calculated with a 95%CI. Chi-square was used for statistical analysis. ResultsThe mean age was 77.3 (±7.0SD) with a mean of 8.9 (±2.8SD) prescribed drugs. IP was higher the greater the number of drugs prescribed (p<0,01). 326 patients (76.4% [95%CI: 72.2 to 80.6]) had at least one IP, according to STOPP/START criteria. STOPP IP affected 51.4% of the patients and START IP 53.6%. The most frequent causes of IP were antiplatelet agents, for both over-prescribing (10.2%) and omission (17.9%). Prolonged use of benzodiazepines (6.6%) and duplications (6.4%) followed in prevalence. ConclusionsIP in polymedicated patients in primary care was very high. IP was similar for drugs that should be withdrawn or started. The most common causes of IP were antiplatelet agents, benzodiazepines and drug duplication.

Impact benzodiazepine dependence on the use of health services: senior’ health study

Prolonged use of benzodiazepines increases the risk of addiction. The impact of this disease on the use of health services by older adults is not known. Examine the association between benzodiazepine dependence and use of health services by older adults in Quebec. Methodology. The data comes from a survey conducted in Quebec in 2005-2006 with a representative sample of 707 elderly benzodiazepine consumption in the community. Benzodiazepine dependence was defined according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Revised Edition. The use of health services as measured by the incidence of consultations with health professionals over a period of 12 months. Seniors have consumed an average daily dose of 6.1 (± 7.6) mg diazepam equivalent to an average of 205 (± 130) days. The prevalence of benzodiazepine dependence has been estimated at 9.5%. This dependence increases the likelihood of consulting a specialist (odds ratio (OR) = 3.42; confidence interval 95% (CI 95%) = 1.38 to 8.50). Visits to other health professionals frontline were not significant. The results of this study suggest that the proportion of seniors who become addicted to benzodiazepines and do not use health services for this condition is important. There is a need to develop programs to improve the quality of benzodiazepine use in this population.

Treatment or “high”: Benzodiazepine use in patients on injectable heroin or oral opioids

Benzodiazepine (BZD) use is widespread among opioid-maintained patients worldwide. We conducted a cross-sectional survey to investigate motives and patterns of BZD use and psychiatric comorbidity in a convenience sample of patients (n=193) maintained on oral opioid agonists or diacetylmorphine (DAM). Prolonged BZD use and high-risk behaviors like parenteral use were common. After principal component analysis, motives were divided into those related to negative affect regulation, positive affect regulation (i.e. reward-seeking) and somato-medical problems. Negative affect regulation and somato-medical motives were associated with prolonged use. Psychiatric comorbidity was associated with several self-therapeutic motives, most importantly to lose anxiety. Patients maintained on DAM were more likely to be ex-users of BZD and report high positive affect regulation. Therefore, patients maintained on different agonists may have deviating motives for BZD use, which could be of importance when addressing this issue. Treatment of psychiatric comorbidity, in particular anxiety, depressive and sleeping disorders, may be helpful in reducing BZD use, particularly in patients maintained on oral opioids.

Level and factors of benzodiazepines misuse in Albania

There is little evidence on benzodiazepine misuse and associated factors in transitional countries of the Western Balkans. The aim of this study was to assess the level and socioeconomic correlates of misuse of benzodiazepine drugs in the Albanian adult population. We conducted a cross-sectional study including a representative sample of 422 individuals (158 men and 264 women) who were benzodiazepines users. A structured questionnaire included data on age, gender, type of drug used, and awareness of possibility to develop dependence and continuation of therapy after prescription. 289 individuals reported treatment continuation compared with 89 participants who reported no continuation of benzodiazepine drugs. There were no significant age group (P = 0.351), sex (P = 0.454), or educational differences (P = 0.117) in treatment continuation. Age was inversely related to the awareness of becoming dependent with the prolonged use of benzodiazepines (78.4% of the persons aged ≤40 years were aware of the dependence versus 51.9% in the age group >40 years; P = 0.002). Our study provides pioneering evidence on the use and misuse of benzodiazepines in Albania. Findings from this study may influence the reforms and policy formulation related to drug misuse in Albania.

Reduction of Group II Metabotropic Glutamate Receptors during Development of Benzodiazepine Dependence

Prolonged use of benzodiazepines often leads to dependence and withdrawal syndrome. However, the cellular mechanisms underlying benzodiazepine dependence have not been fully clarified. Several investigators have shown an involvement of metabotropic glutamate receptors (mGluRs) in the pathophysiology of dependence or withdrawal. This study was performed to elucidate the role of mGluRs in benzodiazepine dependence. Withdrawal signs were precipitated in mice by flumazenil injection (25 mg/kg) after continuous subcutaneous infusion of benzodiazepines for 7 days, and the effects of several Gi-coupled receptor ligands on forskolin-stimulated cyclic AMP accumulation were examined in the cerebral cortex of mice. The mRNA expression for mGluRs was determined by RT-PCR. A single injection of flumazenil precipitated typical withdrawal signs such as tail elevation and tremor in mice treated with diazepam or alprazolam, but not quazepam. The inhibitory effect of nonselective mGluR ligands on adenylate cyclase activity was diminished in mice that showed signs of benzodiazepine withdrawal. The mRNA expression levels of mGluR2 and mGluR3 were lowered in the cerebral cortex of mice pretreated with diazepam or alprazolam. Our findings suggest that the reduction in the expression of group II mGluRs subunits may be involved in the development of benzodiazepine dependence.

Evaluación de la adecuación del tratamiento farmacológico en pacientes pluripatológicos

ObjetiveTo analyze the appropriateness of pharmacotherapy and, if necessary, carry out interventions for its improvement in a cohort of patients with multiple chronic conditions. DesignDescriptive, prospective study of 21 months duration. LocationHospital Universitario Virgen del Rocío. ParticipantsPatients with multiple chronic conditions included in a project for integrated healthcare. MethodsThe primary endpoint was the number of inappropriate treatments. To evaluate the appropriateness of pharmacotherapy, the specialist in hospital pharmacy followed a standardized procedure consisting of the Medication Appropriateness Index (MAI) questionnaire, modified as an implicit method, and the list of criteria of the Screening Tool of Older Person's Potentially Inappropriate Prescription/Screening Tool to Alert doctors to the Right (STOPP-START) as an explicit method. ResultsA total of 244 patients were included, with a mean age of 76 ± 8 (± SD) years. Half (50%) of the patients were men. The mean number of diagnoses per patient was 8 ± 3 (± SD) and 12 ± 4 drugs (± SD). A total of 840 inappropriate treatments were detected, most of them being due to the presence of interactions. The STOPP criteria most not complied with, were duplicate drug class, and prolonged use of benzodiazepines with long half-life or long-acting metabolites, and START for ACE inhibitors in chronic heart failure and statins and antiplatelets in diabetes mellitus, if one or more coexisting risk factors. ConclusionsWe detected a large number of inappropriate treatments. This highlights the importance of evaluating the appropriateness of drug treatment in patients with multiple conditions. It is advisable to use a combined pharmacist intervention strategy that includes both an implicit method and an explicit method.

βCCT, an antagonist selective for α1GABAA receptors, reverses diazepam withdrawal-induced anxiety in rats

The abrupt discontinuation of prolonged benzodiazepine treatment elicits a withdrawal syndrome with increased anxiety as a major symptom. The neural mechanisms underlying benzodiazepine physical dependence are still insufficiently understood. Flumazenil, the non-selective antagonist of the benzodiazepine binding site of GABA(A) receptors was capable of preventing and reversing the increased anxiety during benzodiazepine withdrawal in animals and humans in some, but not all studies. On the other hand, a number of data suggest that GABA(A) receptors containing α(1) subunits are critically involved in processes developing during prolonged use of benzodiazepines, such are tolerance to sedative effects, liability to physical dependence and addiction. Hence, we investigated in the elevated plus maze the level of anxiety 24 h following 21 days of diazepam treatment and the influence of flumazenil or a preferential α(1)-subunit selective antagonist βCCt on diazepam withdrawal syndrome in rats. Abrupt cessation of protracted once-daily intraperitoneal administration of 2 mg/kg diazepam induced a withdrawal syndrome, measured by increased anxiety-like behavior in the elevated plus maze 24 h after treatment cessation. Acute challenge with either flumazenil (10mg/kg) or βCCt (1.25, 5 and 20 mg/kg) alleviated the diazepam withdrawal-induced anxiety. Moreover, both antagonists induced an anxiolytic-like response close, though not identical, to that seen with acute administration of diazepam. These findings imply that the mechanism by which antagonism at GABA(A) receptors may reverse the withdrawal-induced anxiety involves the α(1) subunit and prompt further studies aimed at linking the changes in behavior with possible adaptive changes in subunit expression and function of GABA(A) receptors.

Prolonged use of benzodiazepines is associated with childhood trauma in opioid-maintained patients

BackgroundBenzodiazepine (BZD) misuse in opioid-maintained patients is widespread and has been related to poorer treatment success. Associated factors, in particular, traumatic childhood experiences, have not been investigated extensively. MethodsCross-sectional survey including the childhood trauma questionnaire (CTQ) and clinical data among 193 patients prescribed oral opioids or injectable diacetylmorphine for opioid dependence. ResultsBZD use was prevalent (61%) and the burden of childhood traumatic experiences was high with 67% reporting at least one trauma subscore of moderate-to-severe level. In univariate analysis, CTQ-subcategories “emotional abuse” (p<0.05), “emotional neglect” (p<0.01) and “physical neglect” (p<0.001) were significantly associated with prolonged BZD use. In multivariate analysis, prolonged BZD use was associated with categorized overall CTQ-scores (OR 1.5), HCV-seropositivity (OR 4.0), psychiatric family history (OR 2.3), and opioid dose (mg methadone equivalents, OR 1.010). ConclusionsChildhood traumatic experiences may be associated with prolonged BZD use in opioid-maintained patients and could pose an important starting-point for prevention.