Barriers to conducting deprescribing in the elderly population amid the COVID-19 pandemic

Deprescribing aims to reduce polypharmacy, especially in the elderly population, in order to maintain or improve quality of life, reduce harm from medications, and limit healthcare expenditure. Coronavirus disease (COVID-19) is an infectious disease that has led to a pandemic and has changed the lives many throughout the world. The mode of transmission of this virus is from person to person through the transfer of respiratory droplets. Therefore, non-essential healthcare services involving direct patient interactions, including deprescribing, has been on hiatus to reduce spread. Barriers to deprescribing before the pandemic include patient and system related factors, such as resistance to change, patient's knowledge deficit about deprescribing, lack of alternatives for treatment of disease, uncoordinated delivery of health services, prescriber's attitudes and/or experience, limited availability of guidelines for deprescribing, and lack of evidence on preventative therapy. Some of these barriers can be mitigated by using the following interventions:patient education, prioritization of non-pharmacological therapy, incorporation of electronic health record (EHR), continuous prescriber education, and development of research studies on deprescribing. Currently, deprescribing cannot be delivered through in person interactions, so virtual care is a reasonable alternative format. The full incorporation of EHR throughout Canada can add to the success of this strategy. However, there are several challenges of conducting deprescribing virtually in the elderly population. These challenges include, but are not limited, to their inability to use technology, lack of literacy, lack of assistance from others, greater propensity for withdrawal effects, and increased risk of severe consequences, if hospitalized. Virtual care is the future of healthcare and in order to retain the benefits of deprescribing, additional initiatives should be in place to address the challenges that elderly patients may experience in accessing deprescribing virtually. These initiatives should involve teaching elderly patients how to use technology to access health services and with technical support in place to address any concerns.     

Older adults’ perceptions of deprescribing chronic benzodiazepines

ObjectiveThe primary objective of our study was to explore older adults’ willingness to stop or lower the dose or frequency their chronic benzodiazepine with the long-term goal of developing a patient-centered intervention to support older adults during the deprescribing process.MethodsWe conducted semistructured interviews with adults aged 60 years and older who reported taking a benzodiazepine for at least 3 months. We recruited participants using our institutional research recruitment website between September and November 2019. Eligible participants completed an interview which was audio-recorded and subsequently transcribed. We identified themes related to older adults’ willingness to consider deprescribing their benzodiazepine, if recommended by their prescriber in a hypothetical scenario. Secondary outcomes focused on their use and perceptions of taking a benzodiazepine as well as their experiences attempting to stop the medication.ResultsAmong the 21 participants, most were female (n = 14, 66.7%), white (n = 20, 95.2%), and reported good or fair health (n = 17, 81.0%). More than three-fourths of participants who reported data (n = 14 of 18, 77.8%) had taken a benzodiazepine for 6 or more years. Participants generally reported that the medication was very effective (n = 16, 76.2%) and adverse effects were infrequent (n = 5, 23.8%). Participants varied widely in their attitudes toward the hypothetical questions about changing their current benzodiazepine. A total of 7 people were open to stopping the medication, 4 were willing to potentially consider it, and 10 were resistant. However, most of the participants were open to the idea of de-escalation (n = 17, 81.0%).ConclusionMany older adults were willing to consider deprescribing a long-term benzodiazepine if it were recommended by their prescriber. Older adults were more open to consider lowering the dose or frequency of the chronic benzodiazepine than stopping the medication. Further research is needed to design a patient-centered intervention tool to support prescribers and older adults in deprescribing conversations about benzodiazepines.     

Methods for evaluating the benefit and harms of deprescribing in observational research using routinely collected data

Deprescribing is defined as “the planned and supervised process of dose reduction or stopping of medication that might be causing harm, or no longer be of benefit”. Barriers to deprescribing include healthcare professional fear and lack of guidance. These may stem from limited available evidence on benefits and harms of deprescribing medications commonly used among older persons. Advances in pharmacoepidemiology and causal inference methods to evaluate comparative effectiveness and safety of prescribing medications have yet to be considered for deprescribing medication. This paper discusses select methods and how they can be applied to deprescribing research, using case studies of benzodiazepines and low-dose acetylsalicylic acid (aspirin). Target trial emulation involves the explicit application of design principles from randomised controlled trials to observational studies. Several design aspects, including defining eligibility criteria and time zero, require additional considerations for deprescribing studies. The active comparator new user design also presents challenges, including selection of an appropriate comparator. This paper discusses these aspects, and others, in relation to deprescribing studies. Furthermore, methods proposed to control for confounding, in particular, the prior event rate ratio and propensity scores, are discussed. Introduction of billing codes or mechanisms for accurately determining when deprescribing has occurred would enhance the ability to conduct research using routinely collected data. Although the approaches discussed in this paper may strengthen observational studies of deprescribing, their use may be best suited to certain scenarios or research questions, where randomised controlled trials may be less feasible.     

“I simply don't know,because I don't know which drugs I get”: Perspectives on deprescribing among older adults with limited life expectancy and their relatives

Use of medications of questionable benefit is common in end of life care. In order to effectively carry out deprescribing, it is important to gain insight into the perspectives of patients and their relatives. Thus, our objective was to explore perspectives on deprescribing among older adults with limited life expectancy and their relatives. We conducted semi‐structured interviews with ten nursing home residents and nine relatives. Interviews were analysed using systematic text condensation. Four main themes were identified: “Medication as a necessity and to feel well,” “Frailty as a barrier for taking responsibility,” “Patient autonomy and faith in authority” and “A wish for being involved.” Most participants had not considered the possibility of deprescribing but were open towards medication change if proposed by a healthcare professional. Most participants did not have in‐depth knowledge about medication but would like to be informed or involved in decisions. The participants generally had faith in healthcare professionals despite limited contact. Our study implies that older adults with limited life expectancy and their relatives are generally interested in deprescribing activities; however, the initiative of deprescribing lies with the healthcare professionals.     

Rotarod studies in the rat of the GABAA receptor agonist gaboxadol: lack of ethanol potentiation and benzodiazepine cross-tolerance

All benzodiazepines and benzodiazepine site agonists impair motor performance dose-dependently and potentiate the effects of ethanol. In order to evaluate the risk of benzodiazepine and ethanol interaction with the direct acting GABA(A) receptor agonist 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-ol (gaboxadol), we studied impairment of motor coordination for combinations of gaboxadol, ethanol and a series of benzodiazepines (flunitrazepam, zolpidem and indiplon) in a rat rotarod model. All compounds produced a dose-dependent motor impairment and, in agreement with earlier data, a supra-additive effect of the benzodiazepine ligands and ethanol 1 g/kg was seen. In contrast, no significant potentiation of the effects of gaboxadol by ethanol was detected, and furthermore, no synergistic interaction between gaboxadol and any of the benzodiazepines was seen. A 30-day tolerance study was conducted with daily injections of gaboxadol (7.9 mg/kg) and zolpidem (1.25 mg/kg), respectively. A time-dependent tolerance developed to the motor impairment produced by both compounds. On day 31, cross-tolerance studies between zolpidem/gaboxadol and gaboxadol/zolpidem were conducted. No cross-tolerance was observed, indicating that the motor coordination effects observed with gaboxadol and zolpidem may arise from interaction with different receptor populations.     

Flumazenil's reversal of myoclonic-like movements associated with midazolam in term newborns

Sedation is an important aspect of care for critically ill newborns. Proper sedation reduces stress during procedures such as mechanical ventilation. Midazolam, a short-acting benzodiazepine, is widely administered as a sedative in newborn intensive care units but is not without side effects. Three term newborns developed myoclonic-like abnormal movements after receiving midazolam. In one, flumazenil controlled the abnormal movements. Flumazenil is a potent benzodiazepine antagonist that competitively blocks the central effects of benzodiazepines. It can reverse the sedative effects of benzodiazepines occurring after diagnostic or therapeutic procedures or after benzodiazepine overdose. Flumazenil may be considered in cases of abnormal movements associated with midazolam. However, further studies are needed to provide guidelines for the administration of this drug in newborns.     

Pharmacological profiles in vivo of benzodiazepine receptor ligands

Since the discovery of specific binding sites for benzodiazepines in the brain, a range of compounds have been discovered that do not have the benzodiazepine structure but that do interact with the benzodiazepine receptors. Classical benzodiazepines were considered to be agonists at these receptors. Some compounds only possess part of the profile of classical benzodiazepines and antagonise benzodiazepines in those test procedures in which they are totally inactive. Such compounds are regarded as partial agonists. The discovery of methyl and ethyl β-carboline-3-carboxylate opened a new vista in the pharmacology of benzodiazepine receptors. These agents and now several other compounds act on the benzodiazepine receptors to induce effects functionally opposite to those of classical benzodiazepines (proconvulsant and convulsant) and have been called inverse agonists. Both agonists and inverse agonists can be blocked by compounds with affinity for the receptors but little intrinsic activity (antagonists). A recent increase in the number of benzodiazepine receptor ligands with in vivo activities allows comparison of a range of compounds from several different structral groups. Their pharmacological profiles suggest that these compounds all fit onto a continuum of behavioural effects related to activation of benzodiazepine receptors.     

Testing for benzodiazepine inebriation—relationship between benzodiazepine concentration and simple clinical tests for impairment in a sample of drugged drivers

Objective To study how the various 25 subtests and observations of the Norwegian clinical test for impairment related to the blood benzodiazepine concentrations of apprehended drivers suspected of driving under the influence of benzodiazepines. The impact of single-dose intake in non-daily users of benzodiazepines on the clinical picture of inebriation was also studied.Methods Included in the study were 818 drivers suspected of driving under the influence of non-alcoholic drugs with blood samples containing only one benzodiazepine. We determined which of the 25 subtests and observations of the clinical test for impairment related significantly to the blood benzodiazepine concentrations.Results Significantly related to blood benzodiazepine concentrations were 13 subtests and observations. Of these, 9 withstood adjustment for a variety of background variables. Singledose intake in non-daily users only influenced 3 subtests and observations after adjustment for blood benzodiazepine concentration and background variables. Romberg's test, 1 observation concerning alertness (oriented for time and place), 4 tests on motor and coordination (walk and turn on line, finger-to-nose and finger-to-finger tests), 2 observations on speech (articulation and content) and 1 observation regarding appearance (general conduct) were related to blood benzodiazepine concentrations.Conclusion Many of these simple clinical tests are included in the standardized field sobriety test and are of value in revealing benzodiazepine impairment. The present study offered some possible additions. Combinations of these robust tests can also be used to reveal benzodiazepine inebriation in other contexts.     

Pharmacist interventions to deprescribe opioids and benzodiazepines in older adults: A rapid review

BackgroundMany older adults are prescribed opioids and benzodiazepines (BZDs), despite increased susceptibility to adverse events. Challenges of deprescribing include fragmented care and lack of knowledge or time. Pharmacists are well-positioned to overcome these challenges and facilitate deprescribing of these medications.ObjectivesWe sought to evaluate interventions utilizing pharmacists to deprescribe opioids and BZDs in older adults.MethodsWe conducted a rapid review following a comprehensive literature search to identify interventions with pharmacist involvement for deprescribing opioids and BZDs in older adults. Studies were included based on: (1) inclusion of patients ≥ 65 years old receiving BZDs and/or opioids, (2) evaluation of feasibility or outcomes following deprescribing (3) pharmacists as part of the intervention. We included randomized, observational, cohort, and pilot studies. Studies that did not report specific results for BZD or opioids were excluded.ResultsWe screened 687 abstracts and included 17 studies. Most (n = 13) focused on BZD deprescribing. Few studies focused on opioids (n = 2) or co-prescribing of opioids and BZDs (n = 2). The most common intervention was educational brochures (n = 8), majority being the EMPOWER brochure for deprescribing BZDs. Other interventions included chart review with electronic notes (n = 4), pharmacist-led programs/services (n = 2), and multifactorial interventions (n = 3). Many studies were underpowered or lacked suitable control groups. Generally speaking, interventions utilizing educational materials and those in which pharmacists engaged with patients and providers were more effective. Interventions relying on electronic communication by pharmacists were less successful, due to low acceptance or acknowledgement.ConclusionsWe identified a number of feasible interventions to reduce BZD use, but fewer interventions to reduce opioid use in older adults. An optimal approach for deprescribing likely requires pharmacists to engage directly with patients and providers. Larger well-designed studies are needed to evaluate the effectiveness of deprescribing interventions beyond feasibility.     

Implementing deprescribing guidelines into frontline practice: Barriers and facilitators

A Bruyère Evidence-Based Deprescribing Guideline Symposium was held in March 2018; one component focused on implementing deprescribing guidelines into practice. An interactive discussion activity allowed the 107 participants to share experiences and ideas concerning the barriers and facilitators that arise when moving deprescribing guidelines into frontline practice. Participants identified 8 broad challenges and problem areas. These included challenges and barriers that arise in the daily practices of pharmacists and prescribers and in other health care settings, and those related to existing policies, processes, and financial structures. They also identified 10 factors that facilitated implementation efforts, including: educating patients, caregivers, health care providers (HCPs) and staff; improving collaboration across practice disciplines; expanding the evidence for deprescribing; and fostering organizational cultures of deprescribing. The results indicate that participants are committed to deprescribing and are moving forward with efforts to bring about change. Participants recognize that the implementation of deprescribing is best conceived of as a comprehensive systems change, and that patients and the public need to be involved in deprescribing processes and activities.     

Use of benzodiazepines and benzodiazepine-related drugs among 223 patients with an acute hip fracture in Finland: Comparison of benzodiazepine findings in medical records and laboratory assays

BACKGROUND AND OBJECTIVE: CNS drugs are a risk factor for falls and fractures among older people. Our aim was to describe the use of benzodiazepines and benzodiazepine-related drugs among patients admitted to two Finnish hospitals as a result of an acute hip fracture, and to analyse the concordance of benzodiazepine findings from different data sources. PATIENTS AND METHODS: We studied the use of benzodiazepines and benzodiazepine-related drugs by (i) asking the patient or his/her relatives about his/her use of hypnotics; (ii) checking the patient's medical records; and (iii) analysing for the presence of benzodiazepines in serum and urine. Blood and urine samples were taken at admission. Detection of benzodiazepines in serum and urine was achieved by the fluorescence polarisation method. Concordance in benzodiazepine findings between medical records and laboratory results was estimated by calculating the degree of agreement (kappa) and described graphically using a Venn diagram. RESULTS: A total of 223 patients were enrolled in the study. Of these, 71% were women. The mean age of women was 80.5 years (SD: 10) and of men, 73 years (SD: 12) [p < 0.0001]. Thirty percent of the patients reported that they used hypnotics. Benzodiazepine in serum or urine was detected in 83 (37%) patients. Over half of the patients coming from residential homes (53%) and institutions (54%) were benzodiazepine-positive. For home dwellers the proportion of patients that were benzodiazepine-positive was 29%. In 48% (40/83) of the benzodiazepine-positive patients, the type of benzodiazepine could not be identified because of a lack of drug records regarding benzodiazepines. A total of 113 (51%) patients used benzodiazepines or benzodiazepine-related drugs when both laboratory results and medical drug records were taken into account. Thirty-nine percent of these patients were home dwellers, 69% came from residential care and 76% from institutional care. The concordance between medical records and laboratory results expressed as overlap area was 32% in men and 59% in women, 38% in community-dwelling patients, 63% in residential home patients, and 68% in patients from institutions. CONCLUSION: Half of patients with an acute hip fracture used benzodiazepines or benzodiazepine-related drugs. The highest prevalences were found in institutional and residential care where it should be well known that the use of CNS drugs increases the risk of hip fracture. Concordance of benzodiazepine findings was moderate in all patients and poorest among men. Concordance was poorer among home dwellers than among those living in residential homes and institutions. Analysing benzodiazepine in serum seems to be the most reliable method for ascertaining benzodiazepine exposure. This laboratory test could be performed routinely when the elderly patient is admitted to hospital because of a fall or, at least, in case of hip fracture. Then, if needed, the patient should be informed about the risks of benzodiazepine use, and further falls and fractures could be prevented.     

Deprescribing: An educational imperative

The Bruyère Evidence-Based Deprescribing Guideline Symposium included a forum on health professional education that brought together health professionals, researchers, professional organization representatives and public members. The goal was to facilitate partnerships among educators and to build knowledge, skills and support for behaviour change to integrate the use of evidence-based deprescribing guidelines into health care professional education. Participant discussions were analyzed under the thematic headings of teaching, learning, and assessment, impact of heuristics in learning, the importance of patient/public understanding and the role of leadership in enabling curricular change to include deprescribing. Deprescribing is considered to be on a continuum with prescribing, and it was recognized that related skills are not consistently taught or assessed, which may be interpreted by learners and health professionals as being less important than diagnostic or other skills. Strategies used currently to teach prescribing may also imply that it is a technical skill, not enabling learners to understand that prescribing and deprescribing involve complex tasks requiring patient consultation. Social barriers to deprescribing were also discussed and the importance of patient perspective in teaching prescribing/deprescribing was recognized. Based on the symposium discussions, the authors make several recommendations that include better teaching of optimal prescribing and deprescribing within an interprofessional context, that education be supported from the pre-licensure, post-graduate levels through to continuing professional development, and that assessment, demonstrating competence in prescribing and deprescribing, be embedded within programs.     

Benzodiazepine drugs in general medical patients.

Data from a hospital-based drug surveillance programme were used to determine how often benzodiazepine drugs were used in general medical wards. Benzodiazepines were the drugs most commonly used as hypnotics and were given to 32% of these patients. Concomitant use of more than one benzodiazepine drug or of benzodiazepines with other psychoactive drugs was common and often irrational. A series of double-blind patient-preference studies comparing various benzodiazepines and a benzodiazepine with an antihistamine showed that for short-term hypnotic effect there were no differences between three common benzodiazepines but elderly patients preferred benzodiazepines to the antihistamine, which produced more undesired effects. These results suggest that currently diazepam is the hypnotic of choice for medical ward inpatients.     

Benzodiazepine antagonism by harmane and other beta-carbolines in vitro and in vivo

Harmane and other related beta-carbolines are putative endogenous ligands of the benzodiazepine receptor. Since the compounds are potent convulsants they may have agonist activities at the benzodiazepine receptor while the benzodiazepines may be antagonists. This hypothesis was proved by comparing the in vivo and in vitro antagonism of benzodiazepines by harmane and other beta-carbolines. Harmane is clearly a competitive inhibitor of benzodiazepine receptor binding in vitro. Moreover, harmane-induced convulsions can be inhibited reversibly by diazepam in a manner which is consistent with the assumption of competitive antagonism in vivo. For some beta-carboline derivatives a correlation was found between the affinity for the benzodiazepine receptor in vitro and the convulsive potency in vivo. Thus, the data reported suggest that harmane or other related beta-carbolines are putative endogenous agonists of the benzodiazepine receptor. This suggestion is further supported by the observation that diazepam is equally potent in inhibiting harmane- or picrotoxin-induced convulsions, indicating a convulsive mechanism within the GABA receptor-benzodiazepine receptor system.