Long-term Benzodiazepine Use Research Articles

Prior benzodiazepine use and mortality among adult patients with sepsis: A retrospective population-based cohort study in South Korea.

This study investigated whether long-term benzodiazepine use is associated with increased 90-day mortality among patients with sepsis. A retrospective population-based cohort study based on health records obtained from the National Health Insurance Service database in South Korea was conducted. All adult patients (≥18years) admitted to the hospital with a primary diagnosis of sepsis or septic shock during 2010-2018 were included in the study. Sepsis and septic shock were diagnosed based on the International Classification of Diseases (10th revision: A40, A41 and R65.2). Benzodiazepine users were defined as individuals who were prescribed regular benzodiazepine continuously for over 6months before admission. A total of 251837 patients with sepsis were included in this study, 16686 of which (6.6%) were benzodiazepine users, and 235151 (93.4%) were non-users. After propensity score (PS) matching, 33370 patients (16685 in both groups) were ultimately included. Moreover, following PS matching, the 90-day mortality among benzodiazepine users and non-users was 60.9% (10167) and 41.4% (6916), respectively. Cox regression analysis further revealed the hazard ratio (HR) for 90-day mortality in benzodiazepine users to be 1.75, compared with non-users [95% confidence interval (CI): 1.70-1.81; P<.001]. Sensitivity analyses showed that, compared with non-users, HRs for 90-day mortality in benzodiazepine users without and with other psychiatric illnesses were 1.43 (95% CI: 1.38-1.49; P<.001) and 1.89 (95% CI: 1.84-1.94; P<.001), respectively. Long-term benzodiazepine use is associated with increased 90-day mortality among adult patients with sepsis compared with non-users. This association was more evident in benzodiazepine users with other psychiatric diseases, such as depression or anxiety disorder.

Different Attitudes of Patients and Psychiatrists Toward Benzodiazepine Treatment.

BackgroundConcern regarding the benefit/risk ratio of the long-term use of benzodiazepines (BDZs) and Z-drugs is increasing. To prevent the risk of dependence in BDZ long-term use, it is essential to understand the attitudes of patients and psychiatrists toward BDZ treatment. The aims of this investigation were to 1) obtain information on patients’ attitudes with long-term BDZ use and their referring psychiatrists’ attitudes toward BDZ treatment, including their perception of the difficulty of reducing the dose of BDZs, and 2) identify discrepancies between patients’ and psychiatrists’ perceptions.MethodsA brief questionnaire was constructed to investigate the attitudes of patients receiving BDZ treatment and their referring psychiatrists. Our sample comprised 155 patients who received BDZ treatment for more than one year and their referring eight psychiatrists. Both the patients and their psychiatrists completed our questionnaire between August 2017 and December 2017.ResultsOf the patients, 13% felt that it was more difficult to reduce the dose of BDZs than their referring psychiatrists (type A discrepancy), while 25% felt that it was less difficult (type B discrepancy). In the multivariate logistic regression analysis, the female sex and both the patients’ (“psychotherapy plus BDZs was necessary” and “it was necessary to increase the dose of BDZs”) and psychiatrists’ beliefs (“short-term prescription was justified”) were associated with type A discrepancies. Type B discrepancies were associated with psychiatrists’ beliefs that the patient’s wishes justified the use of BDZs and that the cessation of treatment with BDZs would lead to the deterioration of their rapport with their patients.ConclusionTo overcome the discrepancies in the attitudes of patients and psychiatrists toward the cessation of BDZ treatment, it is necessary to promote patient-centered care involving patient psychoeducation and practice guidelines for the decision-making process. Further studies investigating the promotion of patient-centered care to reduce BDZ use are needed.

Role of the prescriber in supporting patients to discontinue benzodiazepines: a qualitative study.

BackgroundGiven the prevalence of long-term benzodiazepine (BZD) prescribing, increased monitoring through the implementation of prescription monitoring programmes (PMPs) may be the necessary impetus to promote BZD deprescribing. Despite evidence promoting the importance of patient-centred care, GPs have not been sufficiently supported to implement these principles through current deprescribing practice.AimTo investigate patients’ perception of their prescriber’s influence on ceasing BZD use, including their willingness to take their advice, and to understand how a patient’s stage of change influences the barriers and facilitators they perceive to discontinuing BZDs.Design and settingAn online survey and qualitative interviews with 22 long-term users of BZD (≥6 months), aged 18–69 years, recruited from the general population in Victoria, Australia.MethodTwo groups of users of BZD participated, one in the process of reducing their BZD and one not reducing, and were categorised according to their stage of change. Data underwent thematic analysis to identify barriers and facilitators to reducing BZDs both at the patient level and the prescriber level.ResultsBZD patients’ perceptions of the prescriber influence were characterised by prescribing behaviours, treatment approach, and attitude. Barriers and facilitators to reducing their BZD were mapped against their stage of change. Irrespective of their stage of change, participants reported they would be willing to try reducing their BZD if they trusted their prescriber.ConclusionThis study illustrates that, with a few key strategies at each step of the deprescribing conversation, GPs are well positioned to tackle the issue of long-term BZD use in a manner that is patient centred.

Lack of observed tolerance to diazepam nasal spray (Valtoco®) after long-term rescue therapy in patients with epilepsy: Interim results from a phase 3, open-label, repeat-dose safety study

ObjectiveTolerance is a known consideration for maintenance use of benzodiazepines and other antiseizure drugs; however, clinical experience suggests that tolerance may not be anticipated with long-term intermittent use of benzodiazepines as rescue therapy. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation approved for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Reported here are exploratory analyses investigating whether there was evidence of development of tolerance in an interim analysis of a long-term, phase 3, open-label safety study of diazepam nasal spray. MethodsPatients and care partners were trained to administer 5, 10, 15, or 20 mg of diazepam nasal spray (age- and weight-based dosing), with a second dose administered 4–12 hours later if needed. A series of analyses were performed to assess evidence of tolerance using 2 equal, adjacent time periods and data for each patient to compare the proportion of events for which second doses of diazepam nasal spray (as a proxy for effectiveness) were administered in period 1 compared with period 2. ResultsA total of 175 patients were enrolled at interim cutoff, and 158 were treated with diazepam nasal spray for 3370 seizure-cluster events. For 73.4% of patients, duration of exposure to diazepam nasal spray was ≥12 months. A total of 191 analyses were conducted; the proportion of analyses in which second doses in period 2 were lower than in period 1 was 72.8%. Only 5 analyses showed nominally statistically significant changes (P < 0.05); this is fewer than expected by chance, and these differences were not directionally consistent. There was no safety signal with continued use. ConclusionsThese analyses found no statistical evidence of tolerance with the use of diazepam nasal spray over time based on use of a second dose in an initial period of the study compared with a subsequent period for each patient. These results are in agreement with prior studies of benzodiazepine rescue therapy.

Benzodiazepine deprescription strategies in chronic users: a systematic review.

As long-term use of benzodiazepines increases, adverse effects also become more frequent, especially in elderly adults. Due the potential of causing dependence, poor patient adherence and a lack of awareness of side effects, deprescription is challenging. This study aimed to identify what are the effective approaches to motivate and promote deprescription of benzodiazepines. We used MeSH terms to search in five databases that were MEDLINE, Cochrane CENTRAL, LILACS, SCIELO and Science Direct. Then, we selected articles accordingly to inclusion and exclusion criteria. Risk of bias assessment for randomized controlled trials and prospective interventional studies was made using RoB 2.0 and ROBINS-I tools, respectively. For cohort studies, we used the clarity group by McMaster University tool. Database search retrieved 412 results, and 11 studies were selected for analysis. Interventions focusing on patient education to improve community awareness about deprescription presented better discontinuation rates and more potential on motivating discussions about deprescribing with physicians. Interventions based on counselling by different health professionals were not well evaluated as they presented four of six studies as high, serious or critical risk of bias. Although the comparison of different strategies was impaired by the high risk of bias in some studies, patient education focused interventions presented good results. Future studies should consider doing a follow-up of 6 months or longer with evaluation of withdrawal symptoms and sleep patterns, inclusion of young adults on the sample and some form of cognitive evaluation that might influence the results of the intervention.

Prevalence of and factors associated with acute withdrawal symptoms after 24\u2009weeks of eszopiclone treatment in patients with chronic insomnia: a prospective, interventional study

BackgroundAlthough long-term use of benzodiazepines and benzodiazepine receptor agonists (BZDs) has been associated with an increased risk of dependence, the incidence, details of clinical manifestations, and triggering factors of withdrawal symptoms associated with long-term BZD use at common clinical doses remain unclear.MethodsIn a multicenter, open-label study of 123 Japanese patients with insomnia, patients were given a common clinical dose of eszopiclone (2 mg) for 24 weeks, and then treatment was abruptly discontinued. Withdrawal symptoms were evaluated using the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The Insomnia Severity Index (ISI) was used to rate insomnia severity during treatment and 2 weeks after discontinuation. Dependence and poor compliance during treatment without strict medication controls were evaluated with the Benzodiazepine Dependence Self Report Questionnaire short version (Bendep-SRQ SV) subscale sum scores for problematic use, preoccupation, and lack of compliance. Associations between the presence of clinically relevant withdrawal symptoms (BHWSS≥7) and demographic measures, ISI scores at Week 24, and Bendep-SRQ SV subscale sum scores were evaluated by multivariable stepwise logistic regression analyses.ResultsSeventy-six patients completed treatment and 2 weeks of withdrawal; eight (10.5%) had clinically relevant withdrawal symptoms. On multiple logistic regression analysis, Bendep-SRQ SV subscale sum scores were correlated with withdrawal symptoms (odds ratio, 1.650; 95% confidence interval, 1.105–2.464; p = 0.014). Exacerbation of post-discontinuation insomnia was not significantly different between patients who showed clinically relevant withdrawal symptoms and those who did not (p = 0.245).ConclusionsDependence and poor compliance may contribute to withdrawal symptoms with long-term BZD use. Providing guidance to ensure proper compliance is thought to be the best way to mitigate withdrawal symptoms.Trial registrationUMIN000024462 (18/10/2016).

157 Prevalence and Patterns of Drug-Disease Interactions in Long-Term Residents in Nursing Home Facilities in the Czech Republic

Abstract Introduction Prescription of potentially inappropriate medications, non-geriatric doses and drug-disease interactions contribute to high prevalence of adverse drug events, geriatric syndromes and symptoms, and increased frailty in older adults. Despite serious health and socio-economic consequences, a very few studies have been published on phenomenon of prescribing of drug-disease interactions (DDI) in older patients in Central and Eastern Europe. Methods This study aimed to investigate the prevalence of DDI and differences across nursing home (NH) facilities applying relevant parts of Beers 2012 criteria, Czech national consensus 2012 (CNC), and STOPP/START criteria vers.1. This is a retrospective cross-sectional study that analysed semi-implicitly InterRAI-LTC assessment protocols of 490 NH residents from 10 Czech NH facilities (N = 490, 65+) participating in the EU SHELTER project. Retrospective analyses were conducted in 2019 year. Results Prevalence of potentially inappropriate DDI ranged from 44.5% to 62.3% identified by STOPP criteria and CNC, respectively. The most common DDIs were long-term use of benzodiazepines in depressive residents (7.8%) and use of opioids in residents with chronic constipation without osmotic laxative treatment (7.4%). The prevalence of undertreatment identified by START criteria was 52.9%, mainly due to absence of statins in NH residents with diabetes mellitus and cardiovascular risk factors (9.8%) and the absence of anticoagulation therapy in patients with atrial fibrillation (7.1%). Conclusions Potentially inappropriate DDI were highly prevalent in Czech long-term NH residents with significant differences across NH facilities. Using method of semi-implicit medication reviews, we cannot judge the real quality of drug treatment, but there is a necessity to reduce the high prevalence of DDI in NHs in order to prevent potential adverse drug events. Grant support: InoMed project (reg. No: CZ.02.1.01/0.0/0.0/18_069/0010046, 2019–2022), H2020-MCSF-ITN-764632, PROGRESS Q42 FoP, Charles University, FP7-HEALTH-F4–2008-201,917, SVV 260417.

Does cognitive behavioral therapy for anxiety disorders assist the discontinuation of benzodiazepines among patients with anxiety disorders? A systematic review and meta-analysis.

Long‐term use of benzodiazepines (BZD) is not recommended for the treatment of anxiety disorders. Cognitive behavioral therapy (CBT) is an effective treatment option for discontinuation of BZD in patients with anxiety disorders. This systematic review and meta‐analysis sought to clarify whether CBT is effective for discontinuing BZD anxiolytics in patients with anxiety disorders. This study was preregistered with PROSPERO (registration number: CRD42019125263). A literature search of major electronic databases was conducted in December 2018. Three randomized controlled trials were included in this review, and meta‐analyses were performed. The proportion of discontinuing BZD anxiolytics was significantly higher in the CBT plus gradual tapering group than in the gradual tapering alone group, both in the short term (3 months after allocation; number needed to treat: 3.2, 95% confidence interval [CI]: 2.1 to 7.1; risk ratio: 1.96, 95%CI: 1.29 to 2.98, P = 0.002, three studies) and long term (6 to 12 months after allocation; number needed to treat: 2.8, 95%CI: 1.9 to 5.3; risk ratio: 2.16, 95%CI: 1.41 to 3.32, P = 0.0004, three studies). CBT may be effective for discontinuing BZD anxiolytics, both in the short term and in the long term after the allocation. Further studies with larger sample sizes are necessary to draw definitive conclusions regarding the efficacy and safety of CBT for discontinuing BZD anxiolytics in patients with anxiety disorders.

Long-Term Benzodiazepine Prescription During Maintenance Therapy of Individuals With Psychosis Spectrum Disorders-Associations With Cognition and Global Functioning.

BackgroundCognitive difficulties have a significant impact on life functioning and overall well-being in patients with psychosis spectrum disorders (PSDs). There are indications that continuous use of benzodiazepines (BZDs) in various patient groups has a detrimental effect on cognition. Our aim was to explore the association between long-term BZD prescription, global functioning, and cognitive functioning in persons with PSD.MethodsThis exploratory study included 55 PSD patients, recruited from 2 outpatient services in Serbia. Patients were grouped into BZD long-term prescription group and BZD-other group. Brief Psychiatric Rating Scale was used for symptom assessment, functioning was measured by Global Assessment and Functioning Scale, and cognition was assessed by the Global Assessment of Functioning–Cognition in Schizophrenia Scale.ResultsThe sample comprised 52.7% patients who were prescribed with BZD for 6 months or more continually (29/55), with a mean daily dose of 3.16 ± 0.66 mg lorazepam equivalents. There were no differences between study groups in any of the sociodemographic characteristics, duration of illness, or antipsychotic daily dosages. The BZD long-term prescription group had lower global (P < 0.01) and cognitive functioning (P < 0.01), higher Brief Psychiatric Rating Scale scores (1.86 vs 1.58, respectively, P < 0.01), and more psychotropic drugs prescribed on a daily basis than the other group (median: 4 vs 2, respectively, P < 0.01).ConclusionsThe study explored a topic that continues to be underresearched, especially in the Balkans. Prospective studies and comprehensive cognitive batteries are needed to further elucidate the associations between polypharmacy, long-term BZD use, cognitive functioning, and global functioning during maintenance therapy of individuals with PSD.

Age, individual drug associated with long‐term benzodiazepine use

The Brown University Psychopharmacology UpdateVolume 32, Issue 2 p. 7-7 Research Roundup Age, individual drug associated with long-term benzodiazepine use First published: 07 January 2021 https://doi.org/10.1002/pu.30680Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume32, Issue2February 2021Pages 7-7 RelatedInformation

Suicidal Behavior and Medication Adherence in Schizophrenic Patients.

Suicide is one of the potential complications in the Schizophrenic patient population. This review article deals with the significance of antipsychotic medication compliance in decreasing suicidal behavior and hospitalizations in Schizophrenic patients. The medication adherence with second-generation antipsychotics (SGA) like clozapine and long-acting injectables (LAIs) like paliperidone is associated with decrease suicidal behavior and all-cause mortality in Schizophrenic patients. Concomitant treatment of depression and substance abuse disorder in this patient population is also associated with decreasing all-cause mortality and hospitalizations. On the other hand, long-term benzodiazepine use is associated with increase mortality in Schizophrenic patients. We also discuss some important physician intervention strategies to improve medication adherence in Schizophrenic patients like motivational interviewing (MI), behavioral tailoring (BT), and psychosocial interventions like cognitive behavior therapy (CBT).

The effect of concomitant benzodiazepine use on neurocognition in stable, long-term patients with bipolar disorder.

Neurocognitive dysfunction is a common feature of bipolar disorder even in euthymia, and psychopharmacological treatment could have an effect on cognition. Long-term prescription of benzodiazepines in bipolar disorder is a common practice, and their effect on neurocognition has not been well studied in this population. The aim of this study was to evaluate the impact of concomitant benzodiazepine long-term use on neurocognitive function in stable euthymic bipolar disorder patients. Seventy-three euthymic bipolar disorder outpatients and 40 healthy individuals were assessed using a neurocognitive battery. Patients were classified in two groups according to the presence of benzodiazepines in their treatment: the benzodiazepine group (n = 34) and the non- benzodiazepine group (n = 39). Neurocognitive performance was compared between the groups using a multivariate analysis of covariance, considering age, number of depressive episodes, adjuvant antipsychotic drugs, Young Mania Rating Scale score and Hamilton Depression Rating Scale score as covariates. Both bipolar disorder groups (benzodiazepine and non-benzodiazepine) showed an impairment in memory domains (Immediate Visual Memory [p = 0.013], Working Memory [p < 0.001], and Letter-Number Sequence [p < 0.001] from the Wechsler Memory Scale-Revised-III) and slower processing speed functions (Stroop Colour [p < 0.001]) relative to the control group. Nevertheless, the benzodiazepine group showed a greater impairment in executive functions (Conceptual Level Responses [p = 0.024] from the Wisconsin Card Sorting Test and Frontal Assessment Battery [p = 0.042]). Although memory and processing speed impairments were found in bipolar disorder, regardless of their benzodiazepine treatment, benzodiazepine users presented additional neurocognitive impairments in terms of executive functioning. These findings support restricted prescription of benzodiazepines in individuals with bipolar disorder.

Incidence of and Characteristics Associated With Long-term Benzodiazepine Use in Finland

The proportion of patients who develop long-term benzodiazepine use remains controversial, as do the length of time before long-term use develops and the factors associated with long-term use. To investigate the incidence of long-term benzodiazepine and related drug (BZDR) use and factors associated with the development of long-term use implementing a follow-up design with new BZDR users. This population-based cohort study used a nationwide cohort of 129 732 new BZDR users in Finland. New users of BZDRs aged 18 years or older were identified from the prescription register maintained by the Social Insurance Institution of Finland as individuals who initiated BZDR use during 2006 and had not used BZDRs from 2004 to 2005. The follow-up continued until death, long-term hospitalization, a gap of 2 years in BZDR use, or December 31, 2015. The population was analyzed according to age at treatment initiation, categorized into younger (<65 years) and older (≥65 years) subcohorts. Analyses were conducted from May 2019 to February 2020. Use of BZDRs, modeled from register-based data using the PRE2DUP (from prescriptions to drug use periods) method. Long-term BZDR use, defined as continuous use of 180 days or longer, and factors associated with long-term vs short-term use, compared using Cox proportional hazards models. Among the 129 732 incident BZDR users, the mean (SD) age was 52.6 (17.7) years, and 78 017 (60.1%) individuals were women. During the follow-up period, 51 099 BZDR users (39.4%) became long-term users. Long-term treatment was more common in the older subcohort (19 103 individuals [54.5%]) than the younger subcohort (31 996 individuals [33.8%]). At 6 months, 28 586 individuals (22.0%) had become long-term users: 11 805 (33.7%) in the older subcohort and 16 781 (17.7%) in the younger subcohort. The largest proportions of initiators who became long-term users were those persons who initiated treatment with nitrazepam (76.4%; 95% CI, 73.6%-79.1%), temazepam (63.9%; 95% CI, 62.9%-65.0%), lorazepam (62.4%; 95% CI, 59.7%-65.1%), or clonazepam (57.5%; 95% CI, 55.9%-59.2%). Factors associated with the development of long-term use included male sex, older age, receipt of social benefits, psychiatric comorbidities, and substance abuse. The findings of this population-based cohort study conducted in Finland suggest that the incidence of subsequent long-term BZDR use in individuals who initiate use of BZDRs is high, especially among older persons, and that the specific BZDR used initially is associated with the development of long-term BZDR use and should be carefully considered when prescribing BZDRs. The observed factors that appear to be associated with development of long-term BZDR use also should be considered in clinical decision-making when starting and monitoring BZDR treatment.

Association Between Preoperative Benzodiazepine Use and Postoperative Opioid Use and Health Care Costs

The association between preoperative benzodiazepine use and long-term postoperative outcomes is not well understood. To characterize the association between preoperative benzodiazepine use and postoperative opioid use and health care costs. In this cohort study, retrospective analysis of private health insurance claims data on 946 561 opioid-naive patients (no opioid prescriptions filled in the year before surgery) throughout the US was conducted. Patients underwent 1 of 11 common surgical procedures between January 1, 2004, and December 31, 2016; data analysis was performed January 9, 2020. Benzodiazepine use, defined as long term (≥10 prescriptions filled or ≥120 days supplied in the year before surgery) or intermittent (any use not meeting the criteria for long term). The primary outcome was opioid use 91 to 365 days after surgery. Secondary outcomes included opioid use 0 to 90 days after surgery and health care costs 0 to 30 days after surgery. In this sample of 946 561 patients, the mean age was 59.8 years (range, 18-89 years); 615 065 were women (65.0%). Of these, 23 484 patients (2.5%) met the criteria for long-term preoperative benzodiazepine use and 47 669 patients (5.0%) met the criteria for intermittent use. After adjusting for confounders, long-term (odds ratio [OR], 1.59; 95% CI, 1.54-1.65; P < .001) and intermittent (OR, 1.47; 95% CI, 1.44-1.51; P < .001) benzodiazepine use were associated with an increased probability of any opioid use during postoperative days 91 to 365. For patients who used opioids in postoperative days 91 to 365, long-term benzodiazepine use was associated with a 44% increase in opioid dose (additional 0.6 mean daily morphine milligram equivalents [MMEs]; 95% CI, 0.3-0.8 MMEs; P < .001), although intermittent benzodiazepine use was not significantly different (0.0 average daily MMEs; 95% CI, -0.2 to 0.2 MMEs; P = .65). Preoperative benzodiazepine use was also associated with increased opioid use in postoperative days 0 to 90 for both long-term (32% increase, additional 1.9 average daily MMEs; 95% CI, 1.6-2.1 MMEs; P < .001) and intermittent (9% increase, additional 0.5 average daily MMEs; 95% CI, 0.4-0.6 MMEs; P < .001) users. Intermittent benzodiazepine use was associated with an increase in 30-day health care costs ($1155; 95% CI, $938-$1372; P < .001), while no significant difference was observed for long-term benzodiazepine use. The findings of this study suggest that, among opioid-naive patients, preoperative benzodiazepine use may be associated with an increased risk of developing long-term opioid use and increased opioid dosages postoperatively, and also may be associated with increased health care costs.

Is the Long-Term Use of Benzodiazepines Associated With Worse Cognition Performance in Highly Educated Older Adults?

Background: Benzodiazepines (BZD) are common medications for sedative, hypnotic, and anxiolytic that are especially prevalent in older adults. Previous studies have shown that BZD use could impair users' cognition, significantly affecting their quality of life. Past research has shown that higher education might play a protective role in the process of cognitive decline. Very few studies had examined the cognitive effects of BZD on highly educated older adults. The study aimed to explore how cognitive functions would be affected by benzodiazepines among highly educated older adults.Method: 140 older adults with an average education period of 14.8 years were included in this study. The subjects were divided into three separate groups, the long-term BZD users (≥180 days), short-term BZD users (<180 days), and non-users. Demographics and cognitive assessments for the three groups were analyzed using the analysis of variance (ANOVA), the chi-squared test, and the analysis of covariance (ANCOVA). To examine the association between BZD use and cognition a multiple linear aggression approach was used.Result: All three groups were significantly different from each other when looking at executive functioning in the Trail Making Test B (TMT-B). Compared to the control group, short-term BZD users showed significant defects in TMT-B time (p = 0.002) and TMT-B errors (p < 0.001); long-term BZD users showed significant defect on TMT-B time (p = 0.041). Compared to short-term BZD users, long-term BZD users showed significant merit on TMT-B errors (p = 0.001). No significant differences were found in other cognitive tasks that reflected general cognition, verbal memory, language fluency, and visual memory. After adjusting for demographic, increased BZD use over time was positively associated with scores for the revised Brief Visuospatial Memory Test (r = 0.377, p = 0.012).Conclusion: BZD use may be significantly associated with worse executive functioning in highly educated older adults. However, there is no association between the duration of BZD use and increased cognitive deficits in highly educated older adults. This study identified future experimental directions including potential longitudinal studies, within-subject studies comparing mood disorder patients' cognitive performance before and after onset of BZD use, and between-subject studies that directly compare BZD's effect on subjects with the same baseline of cognitive functioning.

Predictive modeling of long-term opioid and benzodiazepine use after intradural tumor resection

BACKGROUND CONTEXTDespite increased awareness of the ongoing opioid epidemic, opioid and benzodiazepine use remain high after spine surgery. In particular, long-term co-prescription of opioids and benzodiazepines have been linked to high risk of overdose-associated death. Tumor patients represent a unique subset of spine surgery patients and few studies have attempted to develop predictive models to anticipate long-term opioid and benzodiazepine use after spinal tumor resection. METHODSThe IBM Watson Health MarketScan Database and Medicare Supplement were assessed to identify admissions for intradural tumor resection between 2007 and 2015. Adult patients were required to have at least 6 months of continuous preadmission baseline data and 12 months of continuous postdischarge follow-up. Primary outcomes were long-term opioid and benzodiazepine use, defined as at least 6 prescriptions within 12 months. Secondary outcomes were durations of opioid and benzodiazepine prescribing. Logistic regression models, with and without regularization, were trained on an 80% training sample and validated on the withheld 20%. RESULTSA total of 1,942 patients were identified. The majority of tumors were extramedullary (74.8%) and benign (62.5%). A minority of patients received arthrodesis (9.2%) and most patients were discharged to home (79.1%). Factors associated with postdischarge opioid use duration include tumor malignancy (vs benign, B=19.8 prescribed-days/year, 95% confidence interval [CI] 1.1–38.5) and intramedullary compartment (vs extramedullary, B=18.1 prescribed-days/year, 95% CI 3.3–32.9). Pre- and perioperative use of prescribed nonsteroidal anti-inflammatory drugs and gabapentin/pregabalin were associated with shorter and longer duration opioid use, respectively. History of opioid and history of benzodiazepine use were both associated with increased postdischarge opioid and benzodiazepine use. Intramedullary location was associated with longer duration postdischarge benzodiazepine use (B=10.3 prescribed-days/year, 95% CI 1.5–19.1). Among assessed models, elastic net regularization demonstrated best predictive performance in the withheld validation cohort when assessing both long-term opioid use (area under curve [AUC]=0.748) and long-term benzodiazepine use (AUC=0.704). Applying our model to the validation set, patients scored as low-risk demonstrated a 4.8% and 2.4% risk of long-term opioid and benzodiazepine use, respectively, compared to 35.2% and 11.1% of high-risk patients. CONCLUSIONSWe developed and validated a parsimonious, predictive model to anticipate long-term opioid and benzodiazepine use early after intradural tumor resection, providing physicians opportunities to consider alternative pain management strategies.

Long-Term Use of Benzodiazepines, Stimulants and Lithium is Not Evidence-Based.

ObjectiveTo study whether three widely differing drug classes, benzodiazepines and similar agents, stimulants and lithium, showed similar patterns of long-term usage.MethodI constructed usage curves over a ten-year period, from 2007 to 2017, based on data from Statistics Denmark.ResultsIn 2007, a total of 478,097 patients deemed a prescription for a benzodiazepine or similar agent, 13,225 for lithium and 8,800 for a stimulant, corresponding to 8.8%, 0.24% and 0.16%, respectively, of the Danish population of 5,427,459 people. Only 6,2102, 5,339 and 983 of these were first-time users (13.0%, 40.4% and 11.2%, respectively). The percentage of current users who redeemed a prescription for the same or a similar drug in each of the following years fell most quickly for benzodiazepines and similar agents and most slowly for lithium, and after ten years, it was 18%, 40% and 29%, respectively.For first-time users, the drop in usage was much quicker. The percentage of first-time users who redeemed a prescription for the same or a similar drug in each of the following years fell to 12%, 59% and 49%, respectively, already after only two years.ConclusionsWe should focus on helping patients withdraw slowly and safely from the drugs they are on instead of telling them that they need to stay on them.

Cost-effectiveness of brief structured interventions to discontinue long-term benzodiazepine use: an economic analysis alongside a randomised controlled trial

Background: In Spain, long-term use of benzodiazepine is prevalent in 7% of the population; however, this longer-term use lacks clinical benefits, costs €90million per year and side-effects further add extra cost through adverse health outcomes. This study aims to estimate the cost-effectiveness of primary care services stepped dose reduction of long-term benzodiazepines using either Structured Interview with Follow-up (SIF) or Without Follow-up (SIW), compared to Treatment as Usual (TAU). Design: Cost-effectiveness analysis was conducted alongside randomised control utilizing data from three arm cluster randomized trial. Setting: Primary care. Participants: 75 general practitioners were randomised to one of the three arms (TAU, SIW, SIF). Measurements: Cost and Cost per Quality-Adjusted Life Year (QALY) Results: Compared to usual care, providing SIW per participant costs an additional €117.94 and adding patient follow-up, €218.4. As a result of intervention, participants showed a gain of, on average, for SIW 0.0144 QALY (95% CI -0.0137 to 0.0425) and for SIF 0.0340 QALYs (0.0069 to 0.0612). The Incremental Cost Effectiveness Ratio was €8190.28/QALY (SIW) and €6423.53/QALY (SIF). At the Spanish reimbursement threshold (€45,000 per QALY) the chance interventions are cost effective is 79.8% for SIW and 97.7% for SIF. Conclusions: Brief structured interventions to discontinue long-term benzodiazepine use represent value for money, particularly with scheduled follow-up appointments, and would represent a cost-effective investment by the Spanish healthcare to reduce prevalence of long-term use.

Assessment of Physician Prescribing of Muscle Relaxants in the United States, 2005-2016

Little is known to date about national trends in the prescribing of skeletal muscle relaxants (SMRs), the use of which is associated with important safety concerns, especially in older adults and in those who use concomitant opioids. To measure national trends in SMR prescribing over a 12-year period. This cross-sectional study used data from the National Ambulatory Medical Care Survey from January 2005 to December 2016. Data were analyzed from August 21, 2018, to July 18, 2019. The study included patients with ambulatory care visits who had encounters with non-federally funded, office-based physicians in the United States. SMR use, categorized as newly prescribed or continued therapy at the office visit. Ambulatory care visits-overall and stratified by calendar year, geographic region, and patient age, sex, and race-in which an SMR was newly prescribed or continued were quantified. Among office visits in which an SMR was newly prescribed, diagnoses were assessed. Concomitant medications were quantified for all office visits, stratified by new or continued therapy. Survey visit weights were used to estimate nationally representative measures, and age-standardized rates were generated by geographic region using US Census data. This study included a total of 314 970 308 office visits (mean [SD] age, 53.5 [15.2] years; 194 621 102 [61.8%] men and 120 349 206 [38.2%] women). In 2016, there were 30 730 262 (95% CI, 30 626 464-30 834 060) US ambulatory care visits in which an SMR was either newly prescribed or continued as ongoing therapy. Patients in these visits were most frequently female (58.2% [95% CI, 57.9%-58.6%]), white (53.7% [95% CI, 53.4%-54.0%]), and aged 45 to 64 years (48.5% [95% CI, 48.2%-48.9%]). During the study period, office visits with a prescribed SMR nearly doubled from 15.5 million (95% CI, 15.4-15.6 million) in 2005 to 30.7 million (95% CI, 30.6-30.8 million) in 2016. Although visits for new SMR prescriptions remained stable, office visits with continued SMR drug therapy tripled from 8.5 million (95% CI, 8.4-8.5 million) visits in 2005 to 24.7 million (95% CI, 24.6-24.8 million) visits in 2016. Older adults accounted for 22.2% (95% CI, 21.8%-22.6%) of visits with an SMR prescription. Concomitant use of an opioid was recorded in 67.2% (95% CI, 62.0%-72.5%) of all visits with a continuing SMR prescription. This study found that SMR use increased rapidly between 2005 and 2016, which is a concern given the prominent adverse effects and limited long-term efficacy data associated with their use. These findings suggest that approaches are needed to limit the long-term use of SMRs, especially in older adults, similar to approaches to limit long-term use of opioids and benzodiazepines.

Benzodiazepines Reduce Relapse and Recurrence Rates in Patients with Psychotic Depression.

The long-term use of benzodiazepines is not recommended for the treatment of major depressive disorder (MDD) due to the risk of adverse effects, including dependence, falls, dementia, mortality and the lack of evidence of effectiveness for symptoms other than anxiety. However, there are many patients with MDD for whom antidepressants are co-administrated with benzodiazepines. This study aimed to identify whether the use of benzodiazepines is associated with a lower risk of relapse or recurrence of MDD in some patients, and the characteristics of these patients. Kaplan–Meier survival analysis was used to quantify the relapse and recurrence of MDD in 108 patients with MDD who achieved remission during hospitalization. Among them, 26 patients had been diagnosed with severe MDD with psychotic features. There was no significant difference in the rate of relapse/recurrence between patients with and without benzodiazepines when all patients were analyzed together. However, among the 26 patients with psychotic depression, 21.2% in the benzodiazepine group and 75.0% in the non-benzodiazepine group experienced relapse (log rank p = 0.0040). Kaplan–Meier survival analysis revealed that this effect was dose-dependent. The adjunctive use of benzodiazepines may reduce relapse/recurrence rates in patients with severe MDD with psychotic features.