-
Critical Care Medicine Sep 2018Benzodiazepine use may be associated with delirium in critically ill children. However, benzodiazepines remain the first-line sedative choice in PICUs. Objectives were... (Observational Study)
Observational Study
OBJECTIVES
Benzodiazepine use may be associated with delirium in critically ill children. However, benzodiazepines remain the first-line sedative choice in PICUs. Objectives were to determine the temporal relationship between administration of benzodiazepines and delirium development, control for time-varying covariates such as mechanical ventilation and opiates, and evaluate the association between dosage of benzodiazepines and subsequent delirium.
DESIGN
Retrospective observational study.
SETTING
Academic tertiary care PICU.
PATIENTS
All consecutive admissions from January 2015 to June 2015.
INTERVENTIONS
Retrospective assessment of benzodiazepine exposure in a population that had been prospectively screened for delirium.
MEASUREMENTS AND MAIN RESULTS
All subjects were prospectively screened for delirium throughout their stay, using the Cornell Assessment for Pediatric Delirium, with daily cognitive status assigned as follows: delirium, coma, or normal. Multivariable mixed effects modeling determined predictors of delirium overall, followed by subgroup analysis to assess effect of benzodiazepines on subsequent development of delirium. Marginal structural modeling was used to create a pseudorandomized sample and control for time-dependent variables, obtaining an unbiased estimate of the relationship between benzodiazepines and next day delirium. The cumulative daily dosage of benzodiazepines was calculated to test for a dose-response relationship. Benzodiazepines were strongly associated with transition from normal cognitive status to delirium, more than quadrupling delirium rates (odds ratio, 4.4; CI, 1.7-11.1; p < 0.002). Marginal structural modeling demonstrated odds ratio 3.3 (CI, 1.4-7.8), after controlling for time-dependent confounding of cognitive status, mechanical ventilation, and opiates. With every one log increase in benzodiazepine dosage administered, there was a 43% increase in risk for delirium development.
CONCLUSIONS
Benzodiazepines are an independent and modifiable risk factor for development of delirium in critically ill children, even after carefully controlling for time-dependent covariates, with a dose-response effect. This temporal relationship suggests causality between benzodiazepine exposure and pediatric delirium and supports limiting the use of benzodiazepines in critically ill children.
Topics: Adolescent; Benzodiazepines; Child; Child, Preschool; Critical Illness; Delirium; Female; Humans; Infant; Male; Retrospective Studies; Time Factors
PubMed: 29727363
DOI: 10.1097/CCM.0000000000003194 -
European Addiction Research 2022Benzodiazepines are widely used in the treatment of anxiety disorders and sleep disturbances, but negative cognitive side effects have been reported after long-term use....
BACKGROUND
Benzodiazepines are widely used in the treatment of anxiety disorders and sleep disturbances, but negative cognitive side effects have been reported after long-term use. Studies on the cognitive effects of long-term benzodiazepine use to date have typically included small samples and limited cognitive assessments.
OBJECTIVES
This study examined cognitive performance on four cognitive domains in long-term benzodiazepine users, compared to normative data. Furthermore, it was examined whether sex, age, benzodiazepine dose, and state and trait anxiety moderated cognitive functioning in long-term benzodiazepine users.
METHODS
Neuropsychological tests targeting different cognitive domains were administered to 92 patients with long-term benzodiazepine use who were accepted for enrolment into a benzodiazepine discontinuation programme in an academic hospital. Test scores were compared to a large normative data sample.
RESULTS
Of the long-term benzodiazepine users, 20.7% could be classified as cognitively impaired across all domains, with the largest effects found in the domains processing speed and sustained attention, and an overall worse performance in women, an effect which appears to be moderated by state anxiety. No effects of age or benzodiazepine dose were found.
CONCLUSIONS
These results extend those of earlier studies on benzodiazepine effects on specific cognitive domains. This study implies an overall detrimental cognitive effect in long-term benzodiazepine users rather than specific effects. Therefore, long-term benzodiazepine use should be avoided, and once present, tailored interventions aimed at tapering benzodiazepines are warranted.
Topics: Anxiety; Attention; Benzodiazepines; Cognition; Female; Humans; Neuropsychological Tests
PubMed: 36041417
DOI: 10.1159/000525988 -
Journal of General Internal Medicine Nov 2022Benzodiazepines and antipsychotics are routinely prescribed for symptom management in hospice. There is minimal evidence to guide prescribing in this population, and...
BACKGROUND
Benzodiazepines and antipsychotics are routinely prescribed for symptom management in hospice. There is minimal evidence to guide prescribing in this population, and little is known about how prescribing varies across hospice agencies.
OBJECTIVE
Examine patient- and hospice agency-level characteristics associated with incident prescribing of benzodiazepines and antipsychotics in hospice.
DESIGN
Retrospective cohort study of a 20% sample of Medicare beneficiaries newly enrolled in hospice.
PARTICIPANTS
Medicare hospice beneficiaries ≥ 65 years old between 2014 and 2016, restricted to those without benzodiazepine (N = 169,688) or antipsychotic (N = 190,441) prescription fills in the 6 months before hospice enrollment.
MAIN MEASURES
The primary outcome was incident (i.e., new) prescribing of a benzodiazepine or antipsychotic. A series of multilevel Cox regression models with random intercepts for hospice agency were fit to examine the association of incident benzodiazepine and antipsychotic prescribing with patient and hospice agency characteristics.
KEY RESULTS
A total of 91,728 (54.1%) and 58,175 (30.5%) hospice beneficiaries were newly prescribed an incident benzodiazepine or antipsychotic. The prescribing rate of the hospice agency was the strongest predictor of incident prescribing: Compared to patients in bottom-quartile benzodiazepine-prescribing agencies, those in top-quartile agencies were 10.7 times more likely to be prescribed an incident benzodiazepine (adjusted hazard ratio [AHR] 10.7, 95% CI 10.1-11.3). For incident antipsychotic prescribing, patients in top-quartile agencies were 51.7 times more likely to receive an antipsychotic (AHR 51.7, 95% CI 44.3-60.4) compared to those in the bottom quartile. Results remained consistent accounting for comfort kit prescribing.
CONCLUSIONS
The pattern of benzodiazepine or antipsychotic prescribing of a hospice agency strongly predicts whether a hospice enrollee is prescribed these medications, exceeding every other patient-level factor. While the appropriate level of prescribing in hospice is unclear, this variation may reflect a strong local prescribing culture across individual hospice agencies.
Topics: Humans; Aged; United States; Benzodiazepines; Antipsychotic Agents; Hospices; Retrospective Studies; Medicare; Practice Patterns, Physicians'
PubMed: 35469359
DOI: 10.1007/s11606-022-07604-3 -
Ugeskrift For Laeger Jan 2017In this review, we summarize the evidence for benzodiazepines and barbiturates as alcohol withdrawal treatment and outline a treatment guideline. A number of randomized... (Review)
Review
In this review, we summarize the evidence for benzodiazepines and barbiturates as alcohol withdrawal treatment and outline a treatment guideline. A number of randomized controlled trials (RCTs) indicate that benzodiazepine treatment decreases alcohol withdrawal seizures and is safe. For barbiturates, only a few RCTs have been undertaken, and barbiturates were not found to be superior to benzodiazepines. Consequently, we suggest that benzodiazepines should still be first-line treatment for alcohol withdrawal.
Topics: Alcohol Withdrawal Delirium; Alcohol Withdrawal Seizures; Barbiturates; Benzodiazepines; Chlordiazepoxide; Humans; Phenobarbital; Risk
PubMed: 28115043
DOI: No ID Found -
Depression and Anxiety Feb 2022Population studies have shown that rates of depressive and anxious symptoms have increased as a result of COVID-19. We analyzed trends in the dispensing rates of...
BACKGROUND
Population studies have shown that rates of depressive and anxious symptoms have increased as a result of COVID-19. We analyzed trends in the dispensing rates of antidepressants and benzodiazepines in Canada to determine whether the pandemic has caused changes in rates of pharmacological treatment for depression and anxiety.
METHODS
We conducted a population-based, cross-sectional time-series analysis of antidepressants and benzodiazepines dispensed monthly by Canadian community pharmacies between January 2017 and December 2020. We used March 2020 as the intervention month to determine if there were any significant changes in the national rate of antidepressant and benzodiazepine tablets dispensed as the result of the COVID-19 pandemic.
RESULTS
There was a temporary reduction in the dispensing rate of antidepressants in April 2020 (from 489 tablets per 100 in March 2020 to 356 tablets per 100 in April 2020; p ≤ .0001); however, the rate returned to its previous level by August 2020. There were no detectable deviations in benzodiazepine dispensing after the declaration of the state of emergency in Ontario.
CONCLUSIONS
Despite the increased reporting of depressive and anxious symptoms during the COVID-19 pandemic, there have been no changes in the dispensing trends of medications used to treat these disorders. As the pandemic continues to evolve, future research is needed to monitor the prevalence of depression and anxiety, and associated medication use, in the Canadian population.
Topics: Antidepressive Agents; Benzodiazepines; COVID-19; Cross-Sectional Studies; Humans; Ontario; Pandemics; SARS-CoV-2
PubMed: 34843627
DOI: 10.1002/da.23228 -
JAMA Network Open Jun 2021Increased use of benzodiazepines has resulted in increasing rates of misuse and adverse effects associated with these drugs. Little is known about the initial exposure...
IMPORTANCE
Increased use of benzodiazepines has resulted in increasing rates of misuse and adverse effects associated with these drugs. Little is known about the initial exposure and source of benzodiazepines among those who use them persistently.
OBJECTIVE
To examine the frequency of use and persistent use of benzodiazepines among patients undergoing major and minor surgical procedures.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included 2 509 599 adult patients who underwent 1 of 11 common surgical procedures in the United States from 2009 to 2017 and were recorded in the MarketScan database. The rates of perioperative and persistent benzodiazepine use were examined in benzodiazepine-naive patients. Data analysis was conducted from July to November 2020.
MAIN OUTCOMES AND MEASURES
Receipt of a perioperative benzodiazepine prescription and persistent use (ie, fill of a second prescription 90-180 days after surgery) among those who received a benzodiazepine perioperatively.
RESULTS
Among 2 509 599 included patients, the mean (SD) age was 54.4 (15.3) years, and 1 596 137 (63.6%) were women. Perioperative benzodiazepine use was noted in 63 931 patients (2.6%). The median (interquartile range) benzodiazepine supply was 10 (5-23) days. Among benzodiazepine-naive patients prescribed a perioperative benzodiazepine, the rate of persistent benzodiazepine use was 19.5% (95% CI, 19.2%-19.8%). During the 90 to 180-day period after surgery, 7013 of 12 468 patients (56.2%) received 1 prescription for benzodiazepines while 5455 (43.8%) received 2 or more prescriptions. Among patients prescribed a benzodiazepine, persistent use was more common in Medicaid recipients (vs patients with commercial insurance: adjusted rate ratio [aRR], 1.29; 95% CI, 1.03-1.62), patients 70 years or older (vs those aged 40-49 years: aRR, 1.14; 95% CI, 1.05-1.23), in women (vs men: aRR, 1.10; 95% CI, 1.06-1.15), in patients with more medical comorbidities (eg, Elixhauser comorbidity score ≥3 vs 0: aRR, 1.11; 95% CI, 1.04-1.19), and in those with diagnoses of anxiety, depression, insomnia or substance use disorder (eg, with vs without anxiety: aRR, 1.43; 95% CI, 1.37-1.50).
CONCLUSIONS AND RELEVANCE
In this study, a relatively small percentage of surgical patients were prescribed benzodiazepines in the perioperative period; however, 1 in 5 of these patients went on to persistent benzodiazepine use.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Benzodiazepines; Cohort Studies; Female; Humans; Male; Middle Aged; Pain, Postoperative; Substance-Related Disorders; United States
PubMed: 34081136
DOI: 10.1001/jamanetworkopen.2021.12478 -
Journal of Pain and Symptom Management May 2019Patients with cancer often experience distressing symptoms such as anxiety or dyspnea, which can be managed with benzodiazepines; however, concerns regarding the impact...
CONTEXT
Patients with cancer often experience distressing symptoms such as anxiety or dyspnea, which can be managed with benzodiazepines; however, concerns regarding the impact of these drugs on survival may dissuade prescribing and compliance.
OBJECTIVES
We aimed to identify and appraise studies examining benzodiazepine use and survival in adults with cancer, to investigate the relationship and context of use.
METHODS
Systematic review of the international literature prepared according to preferred reporting items for systematic reviews. Comprehensive searches of the MEDLINE, Embase, PsycINFO, Cochrane Library, and AMED databases using medical subject heading and free-text search combinations with no date or language restrictions were undertook. Handsearching of references was conducted. Risk of bias of the included studies was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria.
RESULTS
Two thousand two hundred fifty-seven unique records were identified, with 18 meeting inclusion criteria, representing 4117 patients. All studies were very low quality. No study found an increase in mortality in association with benzodiazepine use, whereas two demonstrated an increase.
CONCLUSION
Existing evidence shows no association between benzodiazepine use in patients with cancer and decreased survival. None of the studies evaluated the association between benzodiazepine use and survival in earlier stages of cancer, and the quality of studies retrieved signifies a need for further robust studies to draw more definitive conclusions. Further investigation in patients with cancer using well-designed, high-quality research with survival as a primary outcome should be conducted.
Topics: Benzodiazepines; Humans; Neoplasms
PubMed: 30708126
DOI: 10.1016/j.jpainsymman.2019.01.010 -
PloS One 2023Acute benzodiazepine withdrawal has been described, but literature regarding the benzodiazepine-induced neurological injury that may result in enduring symptoms and life...
BACKGROUND
Acute benzodiazepine withdrawal has been described, but literature regarding the benzodiazepine-induced neurological injury that may result in enduring symptoms and life consequences is scant.
OBJECTIVE
We conducted an internet survey of current and former benzodiazepine users and asked about their symptoms and adverse life events attributed to benzodiazepine use.
METHODS
This is a secondary analysis of the largest survey ever conducted with 1,207 benzodiazepine users from benzodiazepine support groups and health/wellness sites who completed the survey. Respondents included those still taking benzodiazepines (n = 136), tapering (n = 294), or fully discontinued (n = 763).
RESULTS
The survey asked about 23 specific symptoms and more than half of the respondents who experienced low energy, distractedness, memory loss, nervousness, anxiety, and other symptoms stated that these symptoms lasted a year or longer. These symptoms were often reported as de novo and distinct from the symptoms for which the benzodiazepines were originally prescribed. A subset of respondents stated that symptoms persisted even after benzodiazepines had been discontinued for a year or more. Adverse life consequences were reported by many respondents as well.
LIMITATIONS
This was a self-selected internet survey with no control group. No independent psychiatric diagnoses could be made in participants.
CONCLUSIONS
Many prolonged symptoms subsequent to benzodiazepine use and discontinuation (benzodiazepine-induced neurological dysfunction) have been shown in a large survey of benzodiazepine users. Benzodiazepine-induced neurological dysfunction (BIND) has been proposed as a term to describe symptoms and associated adverse life consequences that may emerge during benzodiazepine use, tapering, and continue after benzodiazepine discontinuation. Not all people who take benzodiazepines will develop BIND and risk factors for BIND remain to be elucidated. Further pathogenic and clinical study of BIND is needed.
Topics: Humans; Amnesia; Anxiety; Anxiety Disorders; Control Groups; Benzodiazepines
PubMed: 37384788
DOI: 10.1371/journal.pone.0285584 -
British Journal of Clinical Pharmacology Mar 2020Use and misuse of benzodiazepine might be very prevalent in patients with acute psychiatric symptoms, whereas they might be associated with specific adverse events in...
AIMS
Use and misuse of benzodiazepine might be very prevalent in patients with acute psychiatric symptoms, whereas they might be associated with specific adverse events in this population. The study investigated their prevalence in these patients. Secondary objectives were to identify risk factors for misuse of benzodiazepines, and its impact.
METHODS
A cohort study was based on the hospital's electronic patient records and conducted in patients aged 18 years and over and admitted to a psychiatric hospital. They were followed up for 84 days or until the end of hospitalisation. Four variables of misuse were built: excessive duration of treatment, type of product, excessive dosage and concomitant benzodiazepines. Backward stepwise multivariate logistic regression analysis was used to assess risk factors for each misuse criterion, on the 1 hand, and impact of benzodiazepine misuse, on the other.
RESULTS
In total, 511 psychiatric inpatients were included with 89.0% of them exposed to benzodiazepine. Discharge prescription included no benzodiazepine or a dosage lower than the maximum dosage prescribed during hospitalisation for 78.2% of patients exposed to benzodiazepine during their stay. Of benzodiazepine treatments, 31.4% were associated with at least 1 misuse criterion. Excessive dosage was associated with age ≥65 years (OR 11.57; 95% confidence interval 4.92-27.17), substance/alcohol use disorders (3.35; 95% confidence interval 1.70-6.62) and parenthood (0.49; 0.25-0.97). Some criteria of benzodiazepine misuse were associated with a higher frequency of adverse events occurring after treatment initiation.
CONCLUSIONS
Misuse of benzodiazepines is very common in inpatients with psychiatric disorders. These findings should alert clinicians to comply with clinical recommendations.
Topics: Adolescent; Adult; Aged; Alcoholism; Benzodiazepines; Cohort Studies; Humans; Inpatients; Prescription Drug Misuse; Prevalence
PubMed: 31652345
DOI: 10.1111/bcp.14165 -
Current Opinion in Supportive and... Dec 2018To provide an evidence-based synopsis on the role of benzodiazepines in patients with agitated delirium. (Review)
Review
PURPOSE OF REVIEW
To provide an evidence-based synopsis on the role of benzodiazepines in patients with agitated delirium.
RECENT FINDINGS
Existing evidence supports the use of benzodiazepines in two specific delirium settings: persistent agitation in patients with terminal delirium and delirium tremens. In the setting of terminal delirium, the goal of care is to maximize comfort, recognizing that patients are unlikely to recover from their delirium. A recent randomized trial suggests that lorazepam in combination with haloperidol as rescue medication was more effective than haloperidol alone for the management of persistent restlessness/agitation in patients with terminal delirium. In patients with refractory agitation, benzodiazepines may be administered as scheduled doses or continuous infusion for palliative sedation. Benzodiazepines also have an established role in management of delirium secondary to alcohol withdrawal. Outside of these two care settings, the role of benzodiazepine remains investigational and clinicians should exercise great caution because of the risks of precipitating or worsening delirium and over-sedation.
SUMMARY
Benzodiazepines are powerful medications associated with considerable risks and benefits. Clinicians may prescribe benzodiazepines skillfully by selecting the right medication at the right dose for the right indication to the right patient at the right time.
Topics: Aging; Alcohol Withdrawal Delirium; Antipsychotic Agents; Benzodiazepines; Delirium; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Palliative Care
PubMed: 30239384
DOI: 10.1097/SPC.0000000000000395