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Risk versus risk: A review of benzodiazepine reduction in older adults
Expert Opinion on Drug Safety
Abstract
Introduction:
Benzodiazepines (BZD) are potentially inappropriate for older adults, yet their use persists. Patients and providers may hesitate to discontinue BZDs due to concerns for withdrawal or relapse. We reviewed the literature for BZD reduction protocols to examine common elements, safety and efficacy. A framework is proposed for clinicians to address BZD reduction challenges.
Areas covered:
Following a systematic literature review, this analysis included 28 studies of older out-patients tapering chronic BZDs. Populations included insomnia, depression and anxiety. Protocols included taper alone (32%), taper plus cognitive behavioral therapy (32%) and taper plus medication substitution (36%). Success rates were favorable for all modalities (mean 60%, median 67%, range 25 - 85%) and independent of dose or duration of use. Common schedules included a 25% dose reduction over 1 - 2 weeks until drug-free. Withdrawal symptoms included mainly mild psychological and somatic concerns. No serious safety events were reported.
Expert opinion:
BZD reduction protocols among older adults are feasible and successful. Given unique cognitive and functional abilities and comorbidities of older adults, a patient-centered approach to reduction is needed. Our framework guides clinicians in planning and persisting with BZD reduction, while our checklist addresses tailored tapers. Monitoring and support is emphasized, and taper modifications are proposed for struggling patients.
... In a systematic review of 28 studies by Paquin et al. focussing on tapering BZD in geriatric population, it was revealed that the most common successful tapering protocol included a 25% dose reduction at intervals of 7-14 days until drugfree. 32 The tapering protocols reinforced the importance of flexibility, adjunctive psychotherapy, and an individual-based approach for deprescribing. The most common medication used to facilitate the process included paroxetine, melatonin, valproate/ trazodone, buspirone or progesterone. ...
... The most common medication used to facilitate the process included paroxetine, melatonin, valproate/ trazodone, buspirone or progesterone. 32 Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ), Hopkins Symptom Severity Checklist, Clinical Institute Withdrawal Assessment Benzodiazepine and Benzodiazepine Dependence Self-report Questionnaire were some of the most routinely used tools to screen withdrawal symptoms. 32 A review by Gupta et al. identified seven core aspects of implementing deprescribing in psychiatric clinical practice. ...
... 32 Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ), Hopkins Symptom Severity Checklist, Clinical Institute Withdrawal Assessment Benzodiazepine and Benzodiazepine Dependence Self-report Questionnaire were some of the most routinely used tools to screen withdrawal symptoms. 32 A review by Gupta et al. identified seven core aspects of implementing deprescribing in psychiatric clinical practice. 33 They expanded upon a previously proposed guideline by Reeve et al. 34 and asserted the importance of engaging the patients and their family in shared discussion making and risk-taking 35 , patient-centered approach 36 , and nurturing the qualities of empowerment and hope. ...
Background: Potentially inappropriate medication (PIM) is defined as the usage of a medication for which the risks surpass the perceived benefits, particularly when more efficient alternatives exist. The focus has now shifted from prescribing to deprescribing, especially with one aging. Methods: Based on the Scale for the Assessment of Narrative Review Articles (SANRA) criteria, we performed a search of articles published in Medline and google scholar databases between 2008 and 2022 using terms such as Deprescribing, Psychogeriatric patients, polypharmacy, psychotropic drugs, benzodiazepines, and potentially inappropriate medication (PIM). The initial search yielded 3058 articles. After review, 53 articles were included for discussion. Discussion: Polypharmacy and multimorbidity are multifaceted interconnected concepts in geriatric care that call for timely intervention and interdisciplinary management across each healthcare and social setting. And although the literature and studies on the benefits are variable, deprescribing appears to be overall efficacious. Conclusion: Further research on the efficacy of strategies and existing guidelines in lowering PIMs in geriatric psychiatry patients is warranted. The purpose of this review is to give an outline of the current evidence to inform effective methods for deprescribing PIMs for older persons, with an emphasis on strategies clinicians can use to address challenges to these approaches
... This is consistent with other systematic review evidence demonstrating a mean success rate of 25% to 80% for BZRA tapering (compared with 10% to 20% cessation rates with usual care when deprescribing is not initiated). 39 In general, the decision to continue, reduce, or discontinue a medication is based on a balance of knowledge about its indication and effectiveness, as well as risks of use (actual or potential side effects), drug interactions, pill burden, and cost. Patient or family values and preferences play an important role in shared decision making with regard to continuing, tapering, or stopping medications. ...
... • risks of ongoing BZRA use (eg, falls, memory impairment, motor vehicle accidents) and potential benefits of discontinuation (eg, reduced fall risk, less daytime sedation, improvement in thinking and memory); • therapeutic effect of BZRAs might be lost within 4 weeks owing to receptor changes (but amnestic effects persist) 5 ; and • mild, short-term (a few days to weeks) adverse drug withdrawal effects can be expected during tapering. 39 Our systematic review found that tapering strategies were often accompanied by such brief education interventions informing patients about the withdrawal process, sleep hygiene, and withdrawal symptoms. 28,31 Such engagement strategies (aimed at educating patients regarding BZRA use and involving them in tapering plans) have been employed as part of tapering interventions with success. ...
... In many cases, when withdrawal symptoms occur they are mild and short term (lasting a few days and up to approximately 4 weeks). 39 In studies detailing benzodiazepine withdrawal symptoms, such symptoms tend to appear and peak more quickly (1 to 2 days) and be more severe with abruptly stopping short-acting benzodiazepines compared with after tapering long-acting benzodiazepines (4 to 10 days). 64,65 Gradual taper of short-acting agents does not eliminate withdrawal symptoms but ameliorates their severity, with symptoms beginning to appear once doses are reduced to about 25% of baseline. ...
Objective:
To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop benzodiazepine receptor agonists (BZRAs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes.
Methods:
The overall team comprised 8 clinicians (1 family physician, 2 psychiatrists, 1 clinical psychologist, 1 clinical pharmacologist, 2 clinical pharmacists, and 1 geriatrician) and a methodologist; members disclosed conflicts of interest. For guideline development, a systematic process was used, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence was generated by conducting a systematic review of BZRA deprescribing trials for insomnia, as well as performing a review of reviews of the harms of continued BZRA use and narrative syntheses of patient preferences and resource implications. This evidence and GRADE quality of evidence ratings were used to generate recommendations. The team refined guideline content and recommendations through consensus and synthesized clinical considerations to address front-line clinician questions. The draft guideline was reviewed by clinicians and stakeholders.
Recommendations:
We recommend that deprescribing (tapering slowly) of BZRAs be offered to elderly adults (≥ 65 years) who take BZRAs, regardless of duration of use, and suggest that deprescribing (tapering slowly) be offered to adults aged 18 to 64 who have used BZRAs for more than 4 weeks. These recommendations apply to patients who use BZRAs to treat insomnia on its own (primary insomnia) or comorbid insomnia where potential underlying comorbidities are effectively managed. This guideline does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia.
Conclusion:
Benzodiazepine receptor agonists are associated with harms, and therapeutic effects might be short term. Tapering BZRAs improves cessation rates compared with usual care without serious harms. Patients might be more amenable to deprescribing conversations if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice. This guideline provides recommendations for making decisions about when and how to reduce and stop BZRAs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.
... Slightly less than half of the reviews were limited to patients with specific conditions (33/70, 47 %), most commonly patients with mental disorders (17/70, 24 %), pain (4/70, 6 %), or specific chronic diseases such as diabetes, reflux disease, heart failure and others (Table I). In the older population, the reviews did not focus on a specific disease, with the exception of mental disorders (11)(12)(13)(14)(15)(16), especially dementia and sleep disorders. In the adult population, most reviews focused on mental disorders (17)(18)(19)(20)(21)(22)(23)(24) or chronic medical conditions (5,6,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). ...
... Of the four reviews that addressed populations younger than 18 years, three focused on children and adolescents with mental disorders such as attention-deficit hyperactivity disorder (35,36) or epilepsy (37), and one review focused on paediatric patients with asthma (38). Most reviews focused on a group of medicines, most commonly medicines for mental disorders (15/70, 21 %), in particular benzodiazepines (13,16,(21)(22)(23) and antipsychotics (15,18,35,36). Two other commonly covered groups of medicines were cardiovascular medicines (7/70, 10 %) (39,40), including antihypertensives (11,41,42) or heart failure medicines (29,43), and analgesics (5/70, 7 %), especially opioids (14,27,31,33,34). ...
This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with deprescribing intervention trials (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with medication cessation trials (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with deprescribing intervention trials . Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of medication cessation trials, a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.
... 33,37 Although there is no current standard for tapering benzodiazepines, some providers recommend establishing a longer tapering schedule over 4 to 5 months for older patients and tapering the dose by 25% every 2 weeks. 33,37,38 While tapering health care providers could provide cognitive behavioral therapy for insomnia. 37,38 Nonbenzodiazepine hypnotics reduce sleep latency. ...
... 33,37,38 While tapering health care providers could provide cognitive behavioral therapy for insomnia. 37,38 Nonbenzodiazepine hypnotics reduce sleep latency. 32 These medications, which include eszopiclone, zolpidem, and zaleplon, should be avoided in older adults without consideration of the duration of use (no more than 90 days) because they can cause confusion and they increase the risk of falls and fractures; this should be avoided in older adults with dementia and cognitive impairment. ...
Although insomnia is not a normal part of the aging process, its prevalence increases with age. Factors such as medications and medical and psychiatric disorders can increase the risk for insomnia. In order to diagnose insomnia, it is important for older adults to complete comprehensive sleep and health histories. Cognitive behavioral therapy for insomnia, which includes stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, is the recommended first-line treatment of insomnia and is more effective that medications for the long-term management of insomnia. Medications such as benzodiazepines and antidepressants should be avoided for the treatment of insomnia in older adults.
... Deprescribing can be defined as the process of withdrawal of an inappropriate medication under the supervision of a healthcare professional with the goal of managing polypharmacy and improving outcomes [14]. There is a growing body of evidence that BZRA deprescribing can reduce the risk of harm associated with chronic BZRA use, with no worsening of, or even improvement in, sleep quality, and reduction in anxiety or depression [15][16][17][18]. The success rates reported in older people vary according to the definition of deprescribing (discontinuation only or dose reduction), the setting in which the effects of deprescribing are measured, the nature of the interventions, the type of analysis, and the follow-up duration. ...
... Hospitalisation may be questioned as the best setting for deprescribing of such medication. Indeed, in line of the results of the present study, it represents an opportunity to initiate deprescribing for several reasons [42,48]: 1) Patients can benefit from close monitoring of withdrawal symptoms; 2) frequent diagnoses on admission, such as falls or delirium, may be related to BZRA use before hospitalisation; 3) AGUs provide patientcentred approach, multidisciplinary teams and geriatrician insight, all known to improve deprescribing rates [5,18,34,53]. However, hospitalised patients may experience more anxiety and sleep disorders [51], and have less confidence in healthcare professionals at the hospital than in their general practitioner or usual nursing team. ...
Background
Benzodiazepine receptor agonist (BZRA) use is highly prevalent in hospitalised older people although these drugs are associated with numerous and serious adverse events. Deprescribing can reduce risks associated with chronic BZRA use. The aim of this study was to measure the prevalence of, and factors associated with, BZRA deprescribing in acute geriatric units.
Methods
During a one-year period, this multicentre retrospective study included patients aged ≥70 years, hospitalised in acute geriatric units, and using ≥1 BZRA on admission. BZRA deprescribing at discharge was defined as: ≥25% decrease in lorazepam-equivalent admission dose; discontinuation of all BZRAs; or cessation of a rescue prescription at discharge. BZRA cessation was defined as discontinuation of all BZRAs at discharge. We identified social, medical, geriatric and medication factors associated with BZRA deprescribing using logistic regression.
Results
In total, 561 patients were included (mean age: 85.3±5.9 years, 70% of women). BZRA deprescribing occurred in 240 (42.8%), including 85 with BZRA cessation (15.2%). Deprescribing occurred more frequently in patients with a BZRA-related adverse event on admission or during hospital stay (odds ratio (OR) 4.5; 95% confidence interval [2.6; 7.9]), with an antidepressant (1.6 [1.1; 2.4]) and a higher lorazepam-equivalent dosage on admission (OR 1.2 [1; 1.4]), and less frequently in patients with antipsychotic drug (OR 0.5 [0.3; 0.8]). BZRA cessation was more likely in patients with a BZRA-related adverse event (OR 2.2 [1.2; 4.3]) and a lower lorazepam-equivalent dosage on admission (OR 0.5 [0.3; 0.6]).
Conclusions
During hospitalisation in the acute geriatric units of our hospital, BZRA deprescribing occurred in 42.8% of the patients. Identification of an BZRA-related adverse event by the treating physician appears to be a major factor: this reactive deprescribing accounted for 74% of cases in our study. Further prospective studies are needed to measure long-term persistence of in-hospital deprescribing and encourage proactive management.
... • Medication review and ascertaining reasons for taking each medication; • Calculation of the risk of medication-related harm and possibility of deprescribing; • Assessment of the potential benefits and harm of deprescribing for each medication; • Prioritizing medications with the lowest benefit-harm ratio and adverse withdrawal reactions; • Implementation of the discontinuation program and monitoring its positive and negative effects. 46,47 This process should be individualised based on cognitive and functional abilities and comorbidities of each older adult along with the application of close monitoring, 48,49 given that some older people are open to deprescribing and prefer to play an active role in related decision making, but some others may defer it to their healthcare provider because of lack of knowledge. 50 Moreover, the success of this program depends on the determination of achievable goals and appropriate time planning as well as the creation of psychological preparation in older people. ...
... Stepwise deprescribing interventions for benzodiazepines through pharmacological substitution, psychological support, cognitive-behavioural therapy, education, shared decision making by the pharmacist, physician and older people have been shown to be effective in dose reduction and discontinuation between 27% and 80% of cases. 48,51,52 Also, discontinuation of neuroleptic medications has been shown to have no detrimental effect on functional and cognitive status of older people with long-term mental health conditions. 53 Reduction of antipsychotic medications' use by the older people and prevention of its negative consequences on their health and well-being requires the facilitation of access to non-pharmacological methods including psychotherapy, social interventions, cognitive behavioural therapy, and psychoeducation. ...
Older people with long-term mental health conditions who receive care in their own home are vulnerable to the inappropriate use of medications and polypharmacy given their underlying health conditions and comorbidities. Inappropriate use of pro re nata (PRN) medications in these older people can enhance their suffering and have negative consequences for their quality of life and well-being, leading to readmission to healthcare settings and the increased cost of health care. This narrative review on published international literature aims at improving our understanding of medicines management in home care and how to improve PRN medication use among older people with long-term health conditions in their own home. Accordingly, the improvement of PRN medicines management for these older people requires the development of an individualised care plan considering 'reduction of older people's dependence on PRN medications', 'empowerment of family caregivers', and 'support by healthcare professionals.' PRN medication use should be reduced through deprescription and discontinuation strategies. Also, older people and their family caregivers should be encouraged to prioritize the use of non-pharmacologic methods to relieve physical and psychological problems. Besides the empowerment of family care-givers through role development, education and training about PRN medications, and involvement in decision-making, they need support by the multidisciplinary network in terms of supervision, monitoring, and home visits.
... In a study of 125 patients with an average age of 79 years, using a multidisciplinary team including the patients, deprescribing benzodiazepines or hypnotic agents occurred in 10% of the patients. 83 The team switched patients to a better profile agent (such as a shorter-acting benzodiazepine) in 20% of the cases. 83 When residents and family are unwilling to discontinue benzodiazepines or hypnotics, the provider might change to a safer agent (such as melatonin or a benzodiazepine without active metabolites). ...
... 83 The team switched patients to a better profile agent (such as a shorter-acting benzodiazepine) in 20% of the cases. 83 When residents and family are unwilling to discontinue benzodiazepines or hypnotics, the provider might change to a safer agent (such as melatonin or a benzodiazepine without active metabolites). If patients elect to maintain benzodiazepines or hypnotic agents, oversight groups expect explicit documentation, noting that the patient wishes to maintain benzodiazepine use despite recommendations. ...
Medications to treat disease and extend life in our patients often amass in quantities, resulting in what has been termed “polypharmacy.” This imprecise label usually describes the accumulation of 5, and often more, medications. Polypharmacy in advancing age frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and nonadherence. Polypharmacy is associated with resulting increased hospitalizations and higher costs of care for individuals and health care systems. To reduce polypharmacy, we delineate a systematic, consultative approach to identify highest-risk medications and drug-therapy problems. We address strategic reductions (deprescribing) of medications in palliative care, long-term care, and ambulatory older adults. Best practices for reducing opioids, benzodiazepines, and other high-risk medications include education about risk and agreement by patients and their families, advocates, and care teams. Addressing deprescribing should be within the framework of patients' health status as their care and goals transition from longevity to a plan of maintaining alertness, comfort, and satisfaction of quality of life. A team approach to address polypharmacy and avoidance of high-risk therapy is optimal within long-term care. Patients with terminal illnesses or those moving toward a comfort-care emphasis benefit from medication adjustments that are recognized beneficially within each patient’s care goals. In caring for older adults, the acknowledgement that complicated regimens and high-risk medications requires a care plan to reduce or prevent medication-related problems and costs that are associated with polypharmacy.
... Исследования показывают, что 60-80% пациентов способны прекратить прием BZRA в результате депрескрай-бинга. При этом количество положительных исходов отме-ны препаратов составляет 25-80% при следовании алгорит-му депрескрайбинга и 10-20% без его применения [4]. Окончательное решение о продолжении приема, снижении дозы или отмене BZRA должно быть принято после тща-тельной оценки соотношения риск/польза, при этом нема-ловажно отношение самого пациента или членов его семьи к данной проблеме [4]. ...
... При этом количество положительных исходов отме-ны препаратов составляет 25-80% при следовании алгорит-му депрескрайбинга и 10-20% без его применения [4]. Окончательное решение о продолжении приема, снижении дозы или отмене BZRA должно быть принято после тща-тельной оценки соотношения риск/польза, при этом нема-ловажно отношение самого пациента или членов его семьи к данной проблеме [4]. ...
Deprescribing is the opposite of prescribing drugs, the purpose of which is to improve quality of life and reduce the risk of adverse drug reactions. The paper considers the process of deprescribing benzodiazepines. It analyzes relevant studies on this problem, as well as recommendations to help decide whether it is a need for deprescribing and how to accurately do this. There are also the results of original investigations demonstrating the tapering of benzodiazepine tranquilizers: comparison of simple tampering, use of psychotherapy, or replacement pharmacotherapy. The use of a deprescribing algorithm is the safest way to discontinue benzodiazepines in patients who do not have serious indications for their long-term use.
... Benzodiazepine withdrawal is also feasible without affecting sleep quality or quality of life [92], though withdrawal rates vary according to the interventions and the population (reported rates 27-80%) [93]. As previously described, a multi-component intervention showed a reduction in benzodiazepine use in long-term care following deprescribing recommendations, education for staff, and implementation of 'champion' nurses. ...
... Tapering benzodiazepine use in conjunction with cognitive behaviour therapy may enhance success rates and could be considered for individuals who are more resistant to withdrawal protocols, though this has not been examined specifically in long-term care. Cognitive behaviour therapy may improve some outcomes for people with mild dementia such as clinician-rated anxiety symptoms [51,[93][94][95][96]. Similarly to deprescribing antipsychotics, a personalised person-centred approach is recommended for benzodiazepines, with gradual withdrawal and continued monitoring from a multidisciplinary team [50]. ...
Psychotropic medications have a high risk of serious adverse events and small effect size for changed behaviours for people with dementia. Non-pharmacological approaches are recommended as first-line treatment for changed behaviours, yet psychotropic medications remain highly prevalent in long-term aged care settings. This narrative review describes the current evidence regarding deprescribing psychotropic medications for people with dementia in long-term care. Deprescribing psychotropic medications can be achieved without harm to the person with dementia, and most people experience no withdrawal symptoms. Interventions to deprescribe psychotropic medications should be multifactorial, including lowering the dose of the medication over time, educational interventions and psychological support. However, implementing this is a significant challenge due to the overreliance on psychotropic medications for behavioural management in long-term aged care. Facilitators to deprescribing psychotropic medications in long-term care include multidisciplinary teams with adequate training, education and managerial support, engaging residents and families and change ‘champions’. Deprescribing practices should be person-centred, and an individualised deprescribing protocol should be in place, followed by careful monitoring of the individual. The person with dementia and their family, general practitioner, pharmacist, and allied health and direct care staff should all be involved throughout the deprescribing process. Direct care staff need adequate support, education and training, so they can effectively help the individual and implement person-centred approaches in the absence of psychotropic medications. Effective communication between residents and staff and amongst staff is consistently shown to be an important factor for deciding whether deprescribing of a medication should occur and the successful implementation of deprescribing psychotropic medications.
... [5][6][7][8][9][10][11][12][13] Various strategies have been applied to improve the quality of hypnotic prescription and to withdraw BZDA hypnotics from their chronic users. [14][15][16][17][18][19] In Finland in 2009, that is, when this study was started, sales of BZDA hypnotics were 51.4 defined daily doses (DDD)/1000 inhabitants, and zopiclone and zolpidem together with temazepam accounted for over 90% of the total hypnotic sales. 20 Rebound symptoms, such as exacerbation of insomnia and anxiety, are usual after discontinuation of prolonged BZDA use. ...
... Psychotherapeutic interventions and gradual BZDA dose reduction can alleviate rebound symptoms and improve withdrawal success. [15][16][17][18][19] Only very few controlled studies have involved the effect of withdrawal from the long-term use of BZDA hypnotics on sleep and the quality of life in older people. 21,22 Our purpose was to investigate, as a part of our Satauni-BZDA withdrawal trial, 23 how older chronic BZDA users perceive their sleep and their quality of life before and after successful withdrawal. ...
Long‐term use of benzodiazepines or benzodiazepine receptor agonists is widespread, although guidelines recommend short‐term use. Only few controlled studies have characterized the effect of discontinuation of their chronic use on sleep and quality of life. We studied perceived sleep and quality of life in 92 older (age 55‐91 years) outpatients with primary insomnia before and after withdrawal from long‐term use of zopiclone, zolpidem or temazepam (BZDA). BZDA was withdrawn during one month, during which the participants received psychosocial support and blindly melatonin or placebo. questionnaire was used to study perceived sleep and quality of life before withdrawal, and 1 month and 6 months later. 89 participants completed the 6‐month follow‐up. As melatonin did not improve withdrawal, all participants were pooled and then separated based solely on the withdrawal results at 6 months (34 Withdrawers. 55 Non‐withdrawers) for this secondary analysis. At 6 months, the Withdrawers had significantly (p < 0.05) shorter sleep onset latency and less difficulty in initiating sleep than at baseline and when compared to Non‐withdrawers. Compared to baseline, both Withdwavers and Non‐withdrawers had at 6 months significantly (p < 0.05) less fatigue during the morning and daytime. Stress was alleviated more in Withdrawers than in Non‐withdrawers (p < 0.05). Satisfaction with life and expected health one year later improved (p < 0.05) in Withdrawers. In conclusion, sleep disturbances, day‐time fatigue, and impaired quality of life may resolve within 6 months of BZDA withdrawal. These results encourage withdrawal from chronic use of benzodiazepine‐type hypnotics, particularly in older subjects.
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... Meta-analyses of interventions for reducing inappropriate long-term BZDA use in older adults have shown supervised BZDA withdrawal augmented with psychotherapy to be the most effective intervention, but for pragmatic reasons, a patient-centred approach with individual planning and monitoring or medication reviews is the recommendation [10,11]. Very little data on the long-term persistence of BZDA withdrawal results exist, as most of the follow-ups have been short, 0.5 to 3 months [11]. ...
... According to recent withdrawal studies, spontaneous BZDA withdrawal rate without any interventions ranges from 5 to 26% [10,11,15,24]. The study other than ours with a 3-year follow-up reporting the results of educational withdrawal intervention [15], with one-time counselling or with counselling combined with followup meetings lasting between 2 and 3 weeks, produced respective withdrawal rates of 41 and 39%. ...
Background
Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications. Methods92 outpatients (≥55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9.9 ± 6.2 years), and willingness to withdraw from BZDAs each received either melatonin or a placebo nightly for one month. During this period, BZDAs were meant to be gradually withdrawn. Sleep hygiene counselling and psychosocial support were provided. Three years later, use of BZDAs and other medications was determined by interview and confirmed from medical records. ResultsOf the original 92 outpatients, 83 (90%) participated in the 3-year survey (mean follow-up 3.3 ± 0.2 years). The number of BZDA-free participants decreased from 34 (37%) at 6 months to 26 (28%; intention-to-treat) at 3 years, that of irregular BZDA users decreased from 44 (48%) at 6 months to 27 (29%) at 3 years, while that of regular users increased from 11 (12%) at 6 months to 30 (33%) at 3 years (P = 0.001).Those who were regular BZDA users at 3 years had at baseline (before withdrawal) higher BMI (P = 0.001) than did other participants. At 3 years, the total number of medications remained unchanged for non-users (P = 0.432), but increased for the irregular (P = 0.011) and regular users (P = 0.026) compared to baseline. At 3 years, compared to baseline, use of antidepressants, dopamine agonists, melatonin, and NSAIDs/paracetamol was significantly more common in the whole cohort, but their use did not differ between the BZDA-user subgroups. Randomization to melatonin or placebo during BZDA withdrawal was unrelated to BZDA-withdrawal result. Conclusions
At 3 years after withdrawal, the number of BZDA-free participants had decreased, but still one-third of the subjects remained BZDA-free, and one-third had reduced their use. Successful BZDA withdrawal did not lead to any increase in total number of medications; use of symptomatic medications in the whole cohort, however, did increase.
... Intervention studies on deprescribing show that BZRA withdrawal seems to be feasible and safe in the elderly population despite heterogeneity in the study methodology and outcomes [4], which has been substantiated by three additional systematic reviews on the evidence for interventions to reduce or discontinue BZRA in this age group [10][11][12]. ...
Background/Objectives: The predictors of successful discontinuation of benzodiazepine agonist receptors (BZRA) in elderly patients are not well known due to lack of research on the subject, and there is a need for further investigation, with more focus from the patients’ point of view. No previous studies were identified that have been conducted in Portugal on this subject. We proposed to identify the barriers and facilitators in the discontinuation of BZRA from the perceptions of elderly patients under prolonged prescription of BZRA, belonging to the same rural community. The contributions for further research are intended to be the identification of potential intervention targets directed at patients to reduce the prevalence of elderly patients under prolonged prescription of BZRA. Methods: A set of 15 semi-structured interviews with patients under prolonged prescription of BZRA was conducted. Content analysis was done by the main researcher and a reviewer to identify original emerging themes for the two underlying domains. Results: Four themes were identified as barriers to the discontinuation of BZRA: (1) patient characteristics, (2) clinical factors, (3) medication-related factors, and (4) context and external factors. Seven themes were identified as facilitators to the discontinuation of BZRA: (1) motivation, (2) patients’ knowledge, (3) perception of BZRA insufficiency, (4) access to written information, (5) access to alternatives, (6) time for decision-making, and (7) attitudes of health professionals. Conclusions: The findings highlight the challenging nature of BZRA discontinuation and the range of barriers and facilitators that impact patients’ behaviour towards this purpose. We subdivided the elements identified in two areas, therefore aiming at producing significant knowledge to outline potential intervention targets.
... [1][2][3] However, many people use benzodiazepines for longer periods than recommended by clinical practice guidelines 4-10 and the long-term use of benzodiazepines has been associated with accidents, fractures, cognitive impairment, and dependence. 2 Previous studies have evaluated the challenges with tapering and discontinuing benzodiazepines after chronic use. [11][12][13][14][15][16] However, there is little knowledge of the perspectives of patients about information that would be important to communicate before the consideration of a benzodiazepine. This is important given the lack of knowledge of how to identify individuals who may be at higher risk of using this medication long-term or at risk of experiencing harm from chronic use. ...
Background and Aims
Communicating information about the risks and benefits of benzodiazepines so that it is meaningful to the patient has not been previously described. This study aims to determine patient preferences regarding information received before initiating a benzodiazepine.
Methods
An online survey was distributed through social media and advertisements to Canadians ≥18 years old over a 6‐month period (May–Oct 2022) to collect participant's rating of importance of statements and factors about the risk and benefits of benzodiazepines before initiating treatment using a 10‐point Likert‐type scale. Treatment preferences based on efficacy and risk information were also elicited. The survey was developed and pilot‐tested in collaboration with an advisory committee of individuals with lived and living experience with benzodiazepine use.
Results
Thirty‐seven participants responded to the survey (mean age 30 years old, 81.1% identified as female). The majority of respondents had a history of anxiety (83.8%) or insomnia (32.4%), and 10 (27.0%) respondents had used a benzodiazepine. Patient counseling related to withdrawal symptoms of benzodiazepines, risk of harm in combination with other sedating agents, risk of physical and psychological dependence, and risk of effects on cognition were rated high in the importance of receiving this information before starting a benzodiazepine relative to efficacy endpoints, such as improvement in sleep parameters. When provided with information about the chance of efficacy and risk of harm, 100% would have selected cognitive behavioral therapy as the best treatment option. The most frequently reported source of medication information where patients have sought information was from the internet (25.0%), followed by doctors (21.9%) and pharmacists (18.8%).
Conclusions
This study identified patient important factors and statements viewed as important to communicate before initiating a benzodiazepine. The findings of this survey study will help inform decision‐making when considering treatment options for managing anxiety or insomnia.
... Another systematic review of interventions to deprescribe BZDs and other hypnotics in older adults (>65 years; seven studies) reported that pharmacological substitution or tapering with psychological support was more effective than patient education with tapering, and that deprescribing did not lead to an increase in withdrawal symptoms or a decrease in sleep quality [51]. A systematic review of BZD discontinuation in older adults with insomnia, anxiety, or depression found that all modalities of discontinuation (taper alone, taper plus cognitive behavioral therapy, taper plus medication substitution) were effective, and results were independent of dose or duration of hypnotic use [52]. ...
Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1–2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.
... Examples of benzodiazepine tapers and tips for managing benzodiazepine withdrawal are available (314). Cognitive behavioral therapy increases tapering success rates and might be particularly helpful for patients struggling with a benzodiazepine taper (315). If benzodiazepines prescribed for anxiety are tapered or discontinued, or if patients receiving opioids require treatment for anxiety, evidence-based psychotherapies (e.g., cognitive behavioral therapy), specific antidepressants or other nonbenzodiazepine medications approved for anxiety, or both, should be offered. ...
This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years. It updates the CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016 (MMWR Recomm Rep 2016;65[No. RR-1]:1-49) and includes recommendations for managing acute (duration of <1 month), subacute (duration of 1-3 months), and chronic (duration of >3 months) pain. The recommendations do not apply to pain related to sickle cell disease or cancer or to patients receiving palliative or end-of-life care. The guideline addresses the following four areas: 1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Recommendations are based on systematic reviews of the scientific evidence and reflect considerations of benefits and harms, patient and clinician values and preferences, and resource allocation. CDC obtained input from the Board of Scientific Counselors of the National Center for Injury Prevention and Control (a federally chartered advisory committee), the public, and peer reviewers. CDC recommends that persons with pain receive appropriate pain treatment, with careful consideration of the benefits and risks of all treatment options in the context of the patient's circumstances. Recommendations should not be applied as inflexible standards of care across patient populations. This clinical practice guideline is intended to improve communication between clinicians and patients about the benefits and risks of pain treatments, including opioid therapy; improve the effectiveness and safety of pain treatment; mitigate pain; improve function and quality of life for patients with pain; and reduce risks associated with opioid pain therapy, including opioid use disorder, overdose, and death.
... One systematic review of benzodiazepine taper protocols (28 studies) suggests that for older adults, a taper should reduce the dose by 25% every 1 or 2 weeks until the patient is drug free and states, 'no serious safety events were reported'. 11 About a third (36%) of patients in this review had medication substitution, which may have reduced reported symptoms. Moreover, not all of the studies considered in this review evaluated long-term symptoms. ...
Background
Over 92 million prescriptions for benzodiazepines are dispensed in the United States annually, yet little is known about the experiences of those taking and discontinuing them.
Objective
The aim of this study is to assess the experiences of those taking, tapering, or having discontinued benzodiazepines.
Methods
An online survey ( n = 1207) elicited information about benzodiazepine use, including long-term use, tapering, discontinuation, and withdrawal symptoms.
Results
Symptoms associated with benzodiazepine use, tapering, and discontinuation were numerous and ranged from symptoms such as anxiety, insomnia, and nervousness to digestive problems, irregular heart rhythms, uncontrollable anger, photosensitivity, balance problems, and others. When asked how benzodiazepine symptoms affected their lives, 82.9% reported work problems, 86.3% had problems with social interactions and friendships, and 88.8% had problems with fun, recreation, and hobbies. Suicidal thoughts or attempted suicide was reported by 54.4%, and 46.8% said benzodiazepines caused lost employment. Most of the respondents for whom benzodiazepines were prescribed (76.2%) stated they had not been informed that benzodiazepines were indicated for short-term use only and that discontinuation might be difficult. About a third (31.5%) reported food allergies and/or seasonal allergies that occurred only after benzodiazepine use.
Conclusion
The trajectory of those who taper or discontinue benzodiazepines is unpredictable, and many patients experience a range of protracted and severe symptoms, even years after benzodiazepines were completely discontinued. Greater awareness is needed for both prescribers and patients about the potential for a difficult withdrawal from benzodiazepines.
... If the effect of the intervention is small, or clinic-to-clinic variation is quite large relative to patientlevel variation, this study may be underpowered. However, we view this as unlikely, given the analysis of existing data which support ICCs less than 0.02 and literature which finds similar interventions frequently achieve reductions on MME and DME in excess of 30% [34][35][36][37]. ...
Background
Opioids and benzodiazepines (BZDs) are some of the most commonly prescribed medications that contribute to falls in older adults. These medications are challenging to appropriately prescribe and monitor, with little guidance on safe prescribing of these medications for older patients. Only a handful of small studies have evaluated whether reducing opioid and BZD use through deprescribing has a positive impact on outcomes. Leveraging the strengths of a large health system, we evaluated the impact of a targeted consultant pharmacist intervention to deprescribe opioids and BZDs for older adults seen in primary care practices in North Carolina.
Methods
We developed a toolkit and process for deprescribing opioids and BZDs in older adults based on a literature review and guidance from an interprofessional team of pharmacists, geriatricians, and investigators. A total of fifteen primary care practices have been randomized to receive the targeted consultant pharmacist service (n = 8) or usual care (n = 7). The intervention consists of several components: (1) weekly automated reports to identify chronic users of opioids and BZDs, (2) clinical pharmacist medication review, and (3) recommendations for deprescribing and/or alternate therapies routed to prescribers through the electronic health record. We will collect data for all patients presenting one of the primary care clinics who meet the criteria for chronic use of opioids and/or BZDs, based on their prescription order history. We will use the year prior to evaluate baseline medication exposures using morphine milligram equivalents (MMEs) and diazepam milligram equivalents (DMEs). In the year following the intervention, we will evaluate changes in medication exposures and medication discontinuations between control and intervention clinics. Incident falls will be evaluated as a secondary outcome. To date, the study has enrolled 914 chronic opioid users and 1048 chronic BZD users. We anticipate that we will have 80% power to detect a 30% reduction in MMEs or DMEs.
Discussion
This clinic randomized pragmatic trial will contribute valuable evidence regarding the impact of pharmacist interventions to reduce falls in older adults through deprescribing of opioids and BZDs in primary care settings.
Trial registration
Clinicaltrials.govNCT04272671. Registered on February 17, 2020
... Reduction of inappropriate benzodiazepine prescription is a difficult process, even though several authors report partial successes using tapering protocols in benzodiazepine users supported by education of benzodiazepine users and/or physicians [52][53][54][55][56][57][58]. A French study concluded that a non-specific intervention designed to improve overall NH quality indicators through education and support of NH staff did not decrease benzodiazepine use [59]. ...
An investigation of inappropriate medication use in treatment of depressivity in institutionalized older adults, based on a nurse-led evaluation of functional status and depressive symptoms in nursing home residents. Methods: A cross-sectional multicenter study was performed using records from 1087 residents cared for in fifteen nursing homes (NHs) in the Czech Republic. Inclusion criteria were being a permanent resident of one of the facilities, being 60 years of age or older, having a Geriatric Depression Scale score of 6 or more, and having a Mini Mental State examination score 10 or more. The final sample for analysis included 317 depressed NH residents. Results: 52 percent of NH residents with depressivity had no antidepressant treatment. Benzodiazepines were the only medication in 16 percent of depressed residents, and were added to antidepressant treatment in 18 percent of residents. Benzodiazepine users had significantly higher GDS scores compared to non-users (p = 0.007). Conclusion: More than half of depressed NH residents remained without antidepressant treatment. Residents inappropriately treated with benzodiazepines were more depressed than residents treated with antidepressants only, or even not treated at all. Cooperation of the interprofessional team in the screening of depressive symptoms has the potential to improve the quality of care.
... Based on these meta-analyses, withdrawal from BZD may therefore wrongly appear to be easy. The last two meta-analyses on the topic [84,85] emphasise the effectiveness of supervised withdrawal supported by psychotherapy and in particular the addition of cognitive behavioral therapies. ...
Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk–benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70–80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.
... Even for medications deemed suitable for deprescribing in a patient, it is a complex process that may require more intensive and comprehensive interventions (e.g., integrated interventions that directly engage the patient, prescriber, and pharmacist). Ongoing support may be needed for discontinuation given the risk of physiologic withdrawal, ADWEs, and tapering failure [36]. Patientfocused strategies hold promise in this regard. ...
Background
Falls and fall-related injuries are of growing concern among older adults. Use of fall-risk-increasing drugs (FRIDs) is a potentially modifiable risk factor. This narrative review describes randomized controlled trials that focused on interventions to reduce FRID use and examined fall-related outcomes (e.g., falls, fractures, risk of injury) as the primary outcome.MethodsA comprehensive literature search was conducted to identify eligible studies. Two reviewers screened titles and abstracts and then performed a full-text review of relevant articles. Each study is summarized, and a discussion of strengths and limitations is provided.Results7 of 22 trials were included in this narrative review. Two studies used a computerized decision support intervention, three used a health professional-led (pharmacist or geriatrician) intervention, and two were direct medication withdrawal interventions. Three studies showed a reduction in fall-related outcomes (two identified fall injuries using claims data; one used an injury risk prediction score). Of these, only one reported FRID reduction. Of four studies that did not find a reduction in falls, one study reported a significant reduction in FRIDs, two found no reduction, and one did not report on this outcome. Most interventions consisted of a one-time FRID assessment, and most targeted either providers or patients (not both).Conclusion
Most interventions did not reduce FRID use or change fall-related outcomes. Future studies should test “multi-pronged” intervention strategies that simultaneously target both patients and their providers and include more than a single intervention interaction to reduce this modifiable fall risk factor.
... Wenn in den aktuellen Reviews (Darker, Sweeney, Barry, Farrell & Donnelly-Swift, 2015;Gould, Coulson, Patel, Highton-Williamson & Howard, 2014;Janhsen, Roser & Hoff mann, 2015;Paquin et al., 2014) sowie bei Soyka (2015) davon die Rede ist, dass beim BZD-Entzug im Alter zusätzliche psychotherapeutische Interventionen generell nützlich wären, so wird die Primärliteratur unzutreff end wiedergegeben: Zusätzliche Psychotherapie erhöht nur dann die Erfolgsquote der Entzugsbehandlung, wenn ausgeprägte Angstsymptome oder erhebliche Schlafstörungen zur BZD-Einnahme geführt haben und die Interventionen darauf fokussieren (z. B. Angst: Gosselin, Ladouceur, Morin, Dugas & Baillargeon, 2006;Schlafstörungen: Morin et al., 2004), nicht aber, wenn sie allgemein auf den BZD-Konsum abzielen. ...
Zusammenfassung
Die Verordnung von Benzodiazepinen (BZD) ist in den meisten westlichen Industriestaaten seit mehreren Jahren rückläufig. Entgegengesetzt war die Entwicklung bei den Z-Substanzen (Z-Drugs), wobei sich jedoch dieser Verordnungsanstieg abflachte und – zumindest in Deutschland – in den letzten Jahren die Verordnungen ebenfalls zurückgehen. Die Prävalenzraten zeigen dabei erhebliche regionale Unterschiede. Diese Daten umfassen jedoch nur die Verordnung zu Lasten der gesetzlichen Krankenversicherung bzw. der staatlichen Gesundheitssysteme in den skandinavischen Staaten und Großbritannien. Zumindest in Deutschland gibt es daneben eine beträchtliche Dunkelziffer, weil etwa 30–50% der Verordnungen von BZD und Z-Drugs als Privatrezept erfolgen.
Belastbare bevölkerungsbezogene Daten über die Verbreitung von Missbrauch oder Abhängigkeit von diesen Substanzen gibt es nicht, weil in epidemiologischen Studien keine hinreichend genauen Diagnosen gestellt, sondern lediglich Hinweise auf eine mögliche substanzassoziierte Störung gewonnen werden können. Eine weitere Möglichkeit zur Abschätzung der Verbreitung von Missbrauch oder Abhängigkeit von BZD und Z-Drugs besteht darin, Prävalenzdaten aus der Untersuchung klinischer Stichproben auf die Bevölkerung hochzurechnen.
Dieselben methodischen Einschränkungen gelten auch für Opioidanalgetika. Die Verordnungshäufigkeit hat seit Beginn der 1990er Jahre weltweit z. T. dramatisch zugenommen, wobei die regionalen Unterschiede der Prävalenzraten noch deutlich größer sind als bei BZD und Z-Drugs. Hinsichtlich des Gesamtverbrauchs pro Einwohner belegt Deutschland zusammen mit den USA und Kanada einen Spitzenplatz. Missbrauch und Abhängigkeit (bei Patienten mit chronischen nichttumorbedingten Schmerzen) sind seltener als bei BZD und Z-Drugs. Für alle drei Substanzgruppen gilt, dass Missbrauch und Abhängigkeit im höheren Lebensalter deutlich seltener auftreten.
... During this time, symptoms of preexisting psychiatric conditions may recur, potentially to a greater severity than they did during pretreatment, and may continue for a prolonged period. 23,24 Epileptic seizures and other neuropsychiatric symptoms (psychosis, delirium) may also occur, though they are much less common. 25 Benzodiazepine withdrawal can be divided into the acute and protracted withdrawal phases. ...
... In older adults, weaning chronic benzodiazepines should be considered when age older than 65 and history of at least 1 month of benzodiazepine use [53]. A common schedule includes 25% dose reduction over 1-2 weeks, depending on the half-life of the benzodiazepine, until drug free [54,55]. Different strategies include taper alone, taper plus cognitivebehavioral therapy and taper plus medication substitution. ...
Substance use disorder prevalence in older adults is increasing as the baby boom generation ages. Of the different substances with concern for misuse and use disorder, alcohol, prescription drugs and illicit drugs are the leading causes. High risk drinking and alcohol use disorder is the leading substance use disorder in older adults. Prescription drug misuse and use disorder in older adults is the second leading cause for substance use disorder and most commonly involves prescription opioids and benzodiazepines. Illicit drug use in older adults is also increasing. Substance use disorders are difficult to recognize in older adults due to medical comorbidity, neurocognitive impairment and functional decline. Older adults are also more susceptible to drug effects due to decreased hepatic and renal clearance of the substances. Older adults should be screened and assessed for substance use disorders, and when diagnosed, non-pharmacologic as well as pharmacologic intervention should be performed.
... For certain CNS-active medications, such as benzodiazepines and opioids, ongoing support may be needed for discontinuation given the risk of physiologic withdrawal and tapering failure. 29 Patient-focused strategies hold promise in this regard: Direct-to-patient education about the risks of benzodiazepines has been found to be effective in reducing use. 30 Further, the sample size for these studies was relatively small; therefore, they may have been underpowered to detect a difference in fall rates. ...
OBJECTIVES
To examine: (1) prevalence of fall risk–increasing drug (FRID) use among older adults with a fall‐related injury, (2) which FRIDs were most frequently prescribed, (3) whether FRID use was reduced following the fall‐related healthcare episode, and (4) which interventions have reduced falls or FRID use in older adults with a history of falls.
DESIGN
Systematic review.
PARTICIPANTS
Observational and intervention studies that assessed (or intervened on) FRID use in participants aged 60 years or older who had experienced a fall.
MEASUREMENTS
PubMed and EMBASE were searched through June 30, 2019. Two reviewers independently extracted data and evaluated studies for bias. Discrepancies were resolved by consensus.
RESULTS
Fourteen of 638 articles met selection criteria: 10 observational studies and 4 intervention studies. FRID use prevalence at time of fall‐related injury ranged from 65% to 93%. Antidepressants and sedatives‐hypnotics were the most commonly prescribed FRIDs. Of the 10 observational studies, only 2 used a design adequate to capture changes in FRID use after a fall‐related injury, neither finding a reduction in FRID use. Three randomized controlled studies conducted in various settings (hospital, emergency department, and community pharmacy) with 12‐month follow‐up did not find a reduction in falls with interventions to reduce FRID use, although the study conducted in the community pharmacy setting was effective in reducing FRID use. In a nonrandomized (pre‐post) intervention study conducted in an outpatient geriatrics clinic, falls were reduced in the intervention group.
CONCLUSIONS
Limited evidence indicates high prevalence of FRID use among older adults who have experienced a fall‐related injury and no reduction in overall FRID use following the fall‐related healthcare encounter. There is a need for well‐designed interventions to reduce FRID use and falls in older adults with a history of falls. Reducing FRID use as a stand‐alone intervention may not be effective in reducing recurrent falls.
... After reviewing the full-text versions of these articles, we identified 11 articles that met the inclusion criteria. [17][18][19][20][21][22][23][24][25][26][27] Of these 11 articles, 1 was an older version of a more recent Cochrane SR 26 and 1 was a peer-reviewed journal version of a Cochrane SR. 27 To avoid redundancy, we classified these 2 articles as duplicates. We then assessed the methodological quality of the remaining 9 SRs. ...
Purpose
To systematically evaluate and summarize evidence across multiple systematic reviews (SRs) examining interventions addressing polypharmacy.
Summary
MEDLINE, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (DARE) were searched for SRs evaluating interventions addressing polypharmacy in adults published from January 2004 to February 2017. Two authors independently screened, appraised, and extracted information. SRs with Assessment of Multiple Systematic Reviews (AMSTAR) scores below 8 were excluded. After extraction of relevant conclusions from each SR, evidence was summarized and conclusions compared. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess evidence quality. Six SRs met the inclusion criteria, 4 of which used meta-analytic pooling. Five SRs focused on older adults. Four were not restricted to any specific disease type, whereas 1 focused on proton pump inhibitors and another focused on patients with severe dementia. Care settings and measured outcomes varied widely. SRs examining the impact on patient-centered outcomes, including morbidity, mortality, patient satisfaction, and utilization, found inconsistent evidence regarding the benefit of polypharmacy interventions, but most concluded that interventions had either null or uncertain impact. Two SRs assessing medication appropriateness found very low-quality evidence of modest improvements with polypharmacy interventions.
Conclusion
An overview of SRs of interventions to address polypharmacy found 6 recent and high-quality SRs, mostly focused on older adults, in which both process and outcome measures were used to evaluate interventions. Despite the low quality of evidence in the underlying primary studies, both SRs that assessed medication appropriateness found evidence that polypharmacy interventions improved it. However, there was no consistent evidence of any impact on downstream patient-centered outcomes such as healthcare utilization, morbidity, or mortality.
... Neben den in MEMO 2 beschriebenen Variablen der Psychotherapie mit älteren Menschen, die bei Suchterkrankungen besonders berücksichtigt werden müssen, gibt es einige spezifische Faktoren, die für einen erfolgreichen BDZ-Entzug berücksichtigt werden sollten. Gezieltes Ausschleichen, die Kombination mit kognitiver Verhaltenstherapie und/ oder medikamentöser Substitution führen zu Erfolgsraten, die zwischen 25% und 85% liegen [66]. Metaanalytisch lässt sich die Effektivität für gezielt durchgeführte BDZ-Entzüge bei älteren Patienten vs. «Treatment as usual» gut belegen [67][68][69][70]. ...
... Moreover, BZDs use might be complicated by tolerance and dependence, with subsequent abuse risk in psychiatric patients (Anthierens et al., 2007). Indeed, prolonged self-administration of low doses may be maintained to alleviate withdrawal or relapse symptoms (Bushnell, Stürmer, Gaynes, Pate, & Miller, 2017;Busto & Sellers, 1991;Paquin, Zimmerman, & Rudolph, 2014). ...
Objective
In patients with affective disorders, benzodiazepines (BZDs) are frequently administered at the onset, sometimes inappropriately. We sought to identify clinical variables associated with first BZD prescription in a large sample of patients with affective disorders.
Methods
Four hundred sixty patients with mood or anxiety disorders attending different psychiatric services were assessed comparing those who received BZD as first treatment (BZD w/) and those who did not (BZD w/o).
Results
More than one third (35.7%) of the total sample had received BZDs as first prescription. In relation to mood disorders, BZD w/ subjects more frequently (a) had not a psychiatrist as first therapist, (b) had anxious symptoms at onset, (c) had adjustment disorder as first diagnosis, (d) were treated as outpatients. In relation to specific diagnoses, (a) personal decision of treatment for major depressive disorder, (b) outpatient status for bipolar disorder and (c) longer duration of untreated illness for adjustment disorder were more frequently associated with first BZD prescription. For anxiety disorders, the presence of stressful life events and the diagnoses of panic disorder or specific phobias were more frequently observed in BZD w/ patients.
Conclusion
Patients with affective disorders frequently received BZDs as first prescription with significant differences between and within mood and anxiety disorders.
... 70,71 Severe withdrawal when following planned deprescribing protocol is rare. 53 Gradual tapering of benzodiazepines does not guarantee avoidance of withdrawal symptoms, but serves to reduce the incident risk and severity (if they occur). ...
Long-term benzodiazepine receptor agonist (BZRA) use for insomnia is common and highly prevalent in adults in all care settings. Evidence syntheses suggest that the therapeutic benefits of benzodiazepines for insomnia are marginal and very short term. On the harm side, BZRAs are associated with daytime sedation and confusion. Long-term use increases the risk of falls, fractures, cognitive impairment, and motor vehicle accidents. An evidence-based clinical practice guideline has been developed to assist with deprescribing BZRAs. This review highlights the rationale for deprescribing BZRAs used for insomnia and summarizes key messages for clinicians from the new BZRA deprescribing guideline and their supporting evidence.
... Discontinuation of hypnotics in older people is feasible [9,24,25] and has been associated with cognitive and psychomotor improvement [9]. Since most hypnotics are prescribed by general practitioners (GPs) [22], interventions targeting GPs represent an opportunity to reduce prolonged and inappropriate hypnotic use in older people. ...
Background:
The Australian Government Department of Veterans' Affairs (DVA) Veterans' Medicines Advice and Therapeutics Education Services (Veterans' MATES) programme conducted two intervention (March 2009, follow-up intervention June 2012) both of which aimed to reduce hypnotic use among Australian veterans. We evaluated the effectiveness of the interventions, and estimated the associated health consequences.
Methods:
Both interventions targeted veterans who had been dispensed hypnotics prior to the intervention. Patient-specific prescriber feedback containing patient details and the volume of hypnotics dispensed, along with tailored educational information, was mailed to general practitioners. Veterans, pharmacists and directors of care in residential aged care facilities were mailed tailored educational information. Interrupted time-series and segmented regression modelling were used to determine the effect of the two interventions on the rate of hypnotics dispensing. The cumulative patient-months of hypnotic treatment avoided as a result of the interventions was calculated. We estimated improvements in health consequences of as a result of hypnotic treatment avoided based on the results of cohort studies in the same population identifying the association between hypnotic and sedative use on the outcomes of falls, and confusion.
Results:
After the first Veterans' MATES intervention in March 2009, hypnotic use declined by 0.2% each month, when compared to the baseline level (p = 0.006). The intervention effect was attenuated after one year, and use of hypnotics was found to increase by 0.2% per month after March 2010. Following the second intervention in June 2012, there was a further significant decline in use of 0.18% each month over the 12 months of follow up (p = 0.049). The cumulative effect of both interventions resulted in 20,850 fewer patient-months of treatment with hypnotics. This cumulative reduction in hypnotic use was estimated to lead to a minimum of 1 fewer hospital admissions for acute confusion and 7 fewer hospital admissions due to falls.
Conclusions:
The Veterans' MATES insomnia interventions which involved multiple stakeholders were effective in reducing hypnotic use among older Australians. Repetition of key messages led to sustained practice change.
... Some pharmacologic interventions are also considered effective: for example, the addition of pharmacologic therapies to facilitate BZD discontinuation, gradually reducing the dose, or substitution of a long-acting BZD [40,44,45]. A combination of cognitivebehaviour therapy with BZD dose-tapering or with supervised withdrawal is also considered an effective discontinuation strategy [46,47]. Educational interventions should also be addressed: structured individualized education with dose-tapering and follow-up visits as well as using written instructions are both significantly associated with discontinuation success [43,48,49]. ...
Background
Benzodiazepines are among the most commonly prescribed drugs for anxiety disorders. While they are indicated as adjunctive treatment for short-term use according to clinical practice guidelines, previous studies have shown patterns of long-term use of benzodiazepines, which is problematic due to side effects, dependence and potential of abuse. The aims of this study were to examine among a large sample of primary care adults suffering from anxiety disorders: 1) benzodiazepine use patterns; and 2) correlates of long-term benzodiazepine use.
Methods
Data were drawn from the “Dialogue” project, a large primary care study conducted in 64 primary care clinics in the province of Quebec, Canada. Following a mental health screening in waiting rooms, patients at risk of anxiety or depression completed the Composite International Diagnostic Interview-Simplified (CIDIS). A sample of 740 adults meeting DSM-IV criteria for Generalized Anxiety Disorder, Panic Disorder or Social Anxiety Disorder in the past 12 months took part in this study.
Results
Benzodiazepines were used by 22.6% of participants with anxiety disorders in our primary care sample. A large majority of benzodiazepine users (88.4%) met our indicator of long-term use, as defined by utilization for more than 12 weeks including regular and as-needed use. Based on a logistic regression model, individual correlates associated with long-term benzodiazepine use included: being 30 years or older, having a comorbid physical illness, meeting criteria for comorbid agoraphobia, reporting the use of sleep-aids, and concurrent SSRI utilization.
Limitation
Data collection with self-reported questionnaires may be subject to information bias.
Conclusions
Despite knowledge of the risks of long-term use of benzodiazepines, this remains a pervasive problem. Clinicians need to be mindful of patterns and risk factors leading to long-term use of benzodiazepines in patients with anxiety disorders. Results of this study should raise awareness regarding appropriate prescription practices for benzodiazepines, including decision-making in initiation, duration of prescription, and use of strategies for discontinuation in current long-term benzodiazepine users.
Hypnotic drugs, sleeping pills, or anti-insomnia agents are drugs that promote sleep. In the narrow sense, these are primarily benzodiazepines and benzodiazepine analogs (Z-drugs). Other drugs used to promote sleep include sedative antidepressants and antipsychotics, melatonin receptor agonists, and, more recently introduced, the dual orexin receptor antagonist daridorexant. Despite their widespread use, particularly benzodiazepine and nonbenzodiazepine hypnotics are associated with a high risk of dependence and tolerance development. Tricyclic substances such as antidepressant and antipsychotic drugs often exhibit a broad spectrum of adverse drug reactions, especially when taken over a longer period of time. This article discusses the pharmacological mechanisms, therapeutic applications, risks, and drug interactions of the various hypnotics with regard to metabolization by the cytochrome-P450-system.
Background Benzodiazepine receptor agonists (BZRAs) are commonly prescribed to treat anxiety and insomnia. Although guidelines recommend limiting prescriptions to short-term use (<4 weeks), BZRAs are often continued long-term. Due to the associated risks (e.g. memory impairment, falls/fractures), it is recommended that long-term BZRA use should be discontinued. Several systematic reviews have studied the effectiveness of pharmacological and non-pharmacological interventions targeting long-term BZRA use; however, an overview of the evidence across intervention types and healthcare settings is lacking. Aim To identify and narratively synthesise systematic reviews that assess the effectiveness of interventions targeting the reduction or discontinuation of long-term BZRA use. Methods An overview of systematic reviews will be conducted. Five electronic databases (MEDLINE, Embase, Web of Science, PsycINFO, CINAHL) will be searched for systematic reviews of randomised controlled trials of interventions targeting the reduction or discontinuation of long-term BZRA use in adults in any setting. All types and combinations of interventions are eligible for inclusion (e.g. psychosocial interventions, pharmacological interventions). Interventions will be evaluated against usual care. Article screening and data extraction will be conducted by two reviewers independently. Overlap in primary publications will be assessed by calculating the corrected covered area and graphically represented. Methodological quality of included reviews will be assessed using the AMSTAR-2 tool. Results will be synthesised narratively. The certainty of evidence will be assessed using the GRADE approach. Conclusions This overview of reviews will narratively synthesise the evidence from systematic reviews of the effectiveness of interventions targeting long-term BZRA use. The review will provide an extensive overview of the existing evidence, which will inform future research and policy decisions about interventions for reducing and discontinuing long-term BZRA use.
Benzodiazepine use disorder is a condition characterized by the inappropriate use of benzodiazepine medications. There are special considerations for this disorder in the elderly population, which will be discussed below. A comprehensive assessment of benzodiazepine use disorder includes a thorough history, physical examination, and appropriate laboratory investigations. Treatment of benzodiazepine use disorder consists of assessing the need for continued use of the medication, aggressively treating underlying or comorbid conditions and tapering of the medication. Management may consist of both pharmacological and non-pharmacological interventions. In this chapter, we will review the current recommendations for diagnosing and managing benzodiazepine use disorder in older adults.
Background
High‐risk medications like benzodiazepines, sedative hypnotics, and antipsychotics are commonly prescribed for hospitalized older adults, despite guidelines recommending avoidance. Prior interventions have not fully addressed how physicians make such prescribing decisions, particularly when experiencing stress or cognitive overload. Simulation training may help improve prescribing decision‐making but has not been evaluated for overprescribing.
Methods
In this two‐arm pragmatic trial, we randomized 40 first‐year medical resident physicians (i.e., interns) on inpatient general medicine services at an academic medical center to either intervention (a 40‐minute immersive simulation training) or control (online educational training) groups. The primary outcome was the number of new benzodiazepine, sedative hypnotic, or antipsychotic orders for treatment‐naïve older adults during hospitalization. Secondary outcomes included the same outcome by all providers, being discharged on one of the medications, and orders for related or control medications. Outcomes were measured using electronic health record data over each intern's service period (~2 weeks). Outcomes were evaluated using generalized estimating equations, adjusting for clustering.
Results
In total, 522 treatment‐naïve older adult patients were included in analyses. Over follow‐up, interns prescribed ≥1 high‐risk medication for 13 (4.9%) intervention patients and 13 (5.0%) control patients. The intervention led to no difference in the number of new prescriptions (Rate Ratio [RR]: 0.85, 95%CI: 0.31–2.35) versus control and no difference in secondary outcomes. In secondary analyses, intervention interns wrote significantly fewer “as‐needed” (“PRN”) order types for the high‐risk medications (RR: 0.29, 95%CI: 0.08–0.99), and instead tended to write more “one‐time” orders than control interns, though this difference was not statistically significant (RR: 2.20, 95%CI: 0.60–7.99).
Conclusions
Although this simulation intervention did not impact total high‐risk prescribing for hospitalized older adults, it did influence how the interns prescribed, resulting in fewer PRN orders, suggesting possibly greater ownership of care. Future interventions should consider this insight and implementation lessons raised.
Trial Registration
Clinicaltrials.gov(NCT04668248).
Das Versorgungssystem für Menschen mit alkoholbezogenen Störungen in Deutschland umfasst eine Vielzahl von differenzierten Angeboten, ist jedoch aufgrund historisch gewachsener Strukturen und den spezifischen Zuständigkeiten der Leistungsträger stark fragmentiert. Zu unterscheiden sind die speziell für Menschen mit Störungen durch Alkoholkonsum (SdA) ausgerichteten Systeme der Suchtberatung, der suchtmedizinischen, suchtpsychiatrischen, suchttherapeutischen, und suchtrehabilitativen Behandlung einerseits, von Hilfesystemen mit anderen Schwerpunkten in der Aufgabenstellung, Kompetenz und Verantwortung, wie z. B. medizinische Versorgung (durch niedergelassene ÄrztInnen und Allgemeinkrankenhäuser), die ambulante psychotherapeutische Versorgung, die Altenhilfe, die Jugendhilfe, die Wohnungslosenhilfe, das System der Arbeitslosenhilfen (z. B. Jobcenter, Agenturen für Arbeit) usw. andererseits (DHS, 2019).
Medikamentenbezogene Störungen, beziehungsweise ein schädlicher Gebrauch oder eine Abhängigkeit von Arzneimitteln im Sinne dieser Leitlinie sind Störungen, die im Rahmen einer medizinisch indizierten Therapie mit Arzneimitteln entstehen. Es gibt Wirkstoffe, welche einen schädlichen Gebrauch oder eine Abhängigkeit begünstigen beziehungsweise hervorrufen können. Die Identifikation dieser medikamentenbezogenen Störungen im Versorgungsalltag ist allerdings nicht einfach, was eine verstärkte Aufmerksamkeit aller an der Versorgung Beteiligten auf diese möglichen Probleme erfordert.
Misuse and dependence from sedatives and hypnotics are frequent, especially with benzodiazepines (BZDs) and non-benzodiazepine hypnotics, the so-called Z-drugs (Zolpidem, Zopiclone, Eszopiclone). They are far less toxic than older sedatives and hypnotics and have replaced other drugs such as barbiturates, meprobamate, chloralhydrat, clomethiazole or others. Beside these prescription drugs there also are a number of over-the-counter sedatives with no or very small abuse potential such as various phytotherapeutics, tryptophane, antihistaminergic drugs like diphenhydramine, among others. This chapter will focus on BZDs and Z-drug abuse (harmful use) and dependence.
BZDs and Z-drugs act via inhibitory GABA-receptors in the brain and can induce tolerance, resulting in dose increase, physical and psychological dependence, craving, loss of control and withdrawal symptoms. Predisposing conditions are psychiatric and psychosomatic disorders (especially anxiety, sleep disorders), other substance use disorders, or chronic pain. Many patients with long-term BZD use are women, and elderly.
In case of sudden or even slow discontinuation of long-term medication a broad range of rebound or withdrawal symptoms can emerge including tremor, sweating, inner restlessness, sleep disorders, depression, anxiety, agitation and many others. In case of high dose dependence and more or less abrupt withdrawal more severe symptoms like seizures, psychosis, suicidality or delirium may emerge. A gradual tapering off the medication following long term use is strongly advocated, and the adjunctive pharmacotherapy is symptomatic with no gold standard being established. Psychotherapy depends on the underlying psychiatric or neurological disorder and may include primary care based brief interventions and counselling for the less severe cases and psychoeducation, cognitive behavioral therapy and contingency management for the more severe dependent patients. Although misuse and dependence of BZDs are frequent these patients are less seen in substance use treatment facilities than in primary care or psychiatric and psychosomatic facilities. Possible strategies for prevention and therapy of misuse and dependence of sedatives and hypnotics are discussed.
Disclaimer
In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
Purpose
Patients on hemodialysis have a high risk of medication-related problems. Studies using deprescribing algorithms to reduce the number of inappropriate medications in this population have been published, but none have used a patient-partnership approach. Our study evaluated the impact of a similar intervention with a patient-partnership approach.
Methods
The objective was to describe the implementation of a pharmacist-led intervention with a patient-partnership approach using deprescribing algorithms and its impact on the reduction of inappropriate medications in patients on hemodialysis. Eight algorithms were developed by pharmacists and nephrologists to assess the appropriateness of medications. Pharmacists identified patients taking targeted medications. Following patient enrollment, pharmacists assessed medications with patients and applied the algorithms. With patient consent, deprescription was suggested to nephrologists if applicable. Specific data on each targeted medication were collected at 4 and 16 weeks. Descriptive statistics were used to examine the effects of the deprescribing intervention.
Results
Of 270 patients, 256 were taking at least one targeted medication. Of the 122 patients taking at least one targeted medication who were approached to participate, 66 were included in the study. At enrollment, these patients were taking 252 targeted medications, of which 59 (23.4%) were determined to be inappropriate. Deprescription was initiated for 35 of these 59 medications (59.3%). At 4 weeks, 33 of the 59 medications (55.9%) were still deprescribed, while, at 16 weeks, 27 of the 59 medications (45.8%) were still deprescribed. Proton pump inhibitors and benzodiazepines or Z-drugs were the most common inappropriate medications, and allopurinol was the most deprescribed medication.
Conclusion
A pharmacist-led intervention with a patient-partnership approach and using deprescribing algorithms reduced the number of inappropriate medications in patients on hemodialysis.
Introduction:
Prescribing of medications with well-known adverse effects, like antipsychotics or benzodiazepines, during hospitalization is extremely common despite guideline recommendations against their use. Barriers to optimal prescribing, including perceived pressure from allied health professionals and fatigue, may be particularly pronounced for less experienced medical residents, especially during night shifts when these medications are often prescribed. Under these circumstances, physicians may be more likely to use "quick", often referred to as System 1 choices, rather than "considered" System 2 strategies for decisions. Understanding how medical residents use these different cognitive approaches could help develop interventions to improve prescribing.
Methods:
To understand decision-making and contextual contributors that influence sub-optimal prescribing during night coverage by medical residents, we conducted semi-structured qualitative interviews with residents in general medicine inpatient settings. The interviews elicited perspectives on shift routines, stressful situations, factors influencing prescribing decision-making, and hypothetical measures that could improve prescribing. Interviews were audio-recorded and transcribed. Data were analyzed using codes developed by the team to generate themes using immersion/crystallization approaches.
Results:
We conducted interviews with 21 medical residents; 47% were female, 43% were White, and 43% were Asian. We identified five key themes: (1) time pressures affecting prescribing decisions, (2) fears of judgement by senior physicians and peers and being responsible for patient outcomes, (3) perceived pressure from nursing staff, amplified by nurses' greater experience, (4) clinical acuity as a key factor influencing prescribing, and (5) strategies to improve communication between members of the care team, like ensuring adequate hand-off by day teams.
Discussion:
Medical residents highlighted numerous contextual factors that promote quick thinking rather than slower thinking when prescribing on night shifts, particularly time constraints, perceived pressure, and patient clinical acuity. Interventions aimed at reducing prescribing should address how to manage stress and perceived pressure in decision-making.
The landscape of deprescribing has been rapidly evolving and expanding globally with the formation of regional and national deprescribing networks. The work of these networks is primarily focused on older adults and high-risk medications. The purpose of the current qualitative study is to describe successes and challenges of deprescribing from thought-leaders across the world. Fourteen key informant interviews were conducted from various disciplines, levels of experiences, and regions around the globe. From the interviews, six major themes across two domains were identified: (a) network structure, (b) public perception, (c) policy implications, (d) implementation, (e) challenges, and (f) recommendations. These domains, themes, and insight provided by deprescribing leaders contribute to the advancement of deprescribing networks as global efforts continue to focus on optimizing medication management. Collaboration among interprofessional team members will be critical to the expansion as well as sustainability of this important work. [Journal of Gerontological Nursing, 48(1), 7-14.].
Objective
To measure the incidence of long-term benzodiazepine receptor agonist (BZRA) use among individuals with anxiety, mood and/or sleep disorders. To identify factors associated with long-term use following the first prescription.
Methods
This was a population-based retrospective cohort study using administrative databases in Manitoba, Canada. Individuals with anxiety/mood or sleep disorder who received their first BZRA between 1 April 2001 and 31 March 2015 were included. Long-term use was defined as ≥180 days. Logistic regression modelling was used to examine predictors of long-term use.
Results
Among 206 933 individuals included, long-term BZRA use in the first episode of use was 4.5% (≥180 days) following their first prescription. Factors associated with ≥180 days of use included male sex (adjusted OR (aOR) 1.33, 95% CI 1.27 to 1.39), age ≥65 (aOR 5.15, 95% CI 4.81 to 5.52), income assistance (aOR 1.68, 95% CI 1.55 to 1.81), previous non-BZRA psychotropic (aOR 1.93, 95% CI 1.83 to 2.02) or opioid use (aOR 1.16, 95% CI 1.11 to 1.22), high comorbidity (aOR 1.43, 95% CI 1.32 to 1.55), high healthcare use (aOR 1.46, 95% CI 1.33 to 1.60) and psychiatrist prescriber (aOR 2.11, 95% CI 1.93 to 2.32).
Conclusions
Less than 1 in 20 patients use BZRAs ≥180 days in their first treatment episode. Several factors were associated with long-term use following the first prescription and further investigation into whether these factors need to be considered at the point of prescribing is warranted. In light of these findings, future research should examine the predictors of cumulative repeat episodes of BZRA exposure.
In this chapter, we review the evidence-based management and treatment of anxiety disorders in the geriatric population. This will include adverse effects and alternative uses of anxiolytic medications.
Benzodiazepines and related compounds (benzodiazepine receptor agonists [BzRAs]) cause a wide range of adverse reactions, including withdrawal symptoms, even when normal or low dosages are used. Deprescribing is recommended when there is loss of efficacy, major side effects, or use longer than four weeks. The withdrawal syndrome is due to physiologic dependence based on various receptor adaptations. Psychological, neurophysiologic, and somatic complaints can be misdiagnosed as psychiatric, psychosomatic, or substance use disorder. These symptoms may be severe and prolonged. The discontinuation process should include careful planning, support, and the use of cognitive behavioral therapy. Tapering, perhaps after substituting with a long-acting BzRA, should be patient-led and proceed slowly, anticipating completion over 12 to 18 months or even longer. In a proportion of patients, symptoms may continue months or years after complete BzRA cessation, requiring ongoing medical care.
The cause of prolonged or recurrent symptoms following the cessation of long-term benzodiazepine use is proposed to be related to downregulation and allosteric decoupling of the γ-aminobutyric acid/benzodiazepine receptor complex. This case series describes 2 patients with prolonged (>2 weeks) recurrent complications during attempted tapering of benzodiazepine doses after long-term treatment. Excited catatonia developed in a 90-year-old woman, and prolonged delirium developed in a 69-year-old woman. Both patients showed improvement of symptoms after resumption of higher doses of benzodiazepine treatment and recurrence of symptoms when the dose was again lowered. Caution should be exercised regarding the long-term use of benzodiazepines in older adults (aged ≥65 years). Tapering of benzodiazepines in older patients after long-term treatment may require slow decreases in dose over long periods. Psychotherapeutic interventions, such as brief cognitive therapy with psychoeducation and motivational enhancement, and osteopathic manipulative treatment to decrease paravertebral muscle tension may be beneficial during the tapering process.
Benzodiazepines (BZDs) lose their benefits as anxiolytics and sedatives with longer-term use, due to the development of tolerance, as well as the development of harms (e.g. dependence, impaired cognition and other CNS effects). Older patients are at increased risk of BZD-related harms, including fractures and falls. Deprescribing BZDs in this patient population should be done slowly to avoid withdrawal syndrome, and should use a multifaceted stepwise approach.
Points essentiels
Toutes les benzodiazépines et les médicaments apparentés possèdent des effets pharmacodynamiques soumis à tolérance. Cette tolérance pharmacologique aux benzodiazépines peut se manifester rapidement, entre une semaine et un mois, et concerne en particulier les propriétés hypnotiques et anxiolytiques.
Des études anciennes ont montré une réelle mais faible efficacité à court terme des benzodiazépines sur l’anxiété et les troubles du sommeil.
L’efficacité à long terme des benzodiazépines peut se confondre avec la survenue d’effets rebond, de symptômes de sevrage ou d’une rechute à l’arrêt qui contribuent à une apparence d’efficacité, d’autant que la réintroduction du médicament va supprimer ces symptômes.
Il existe une tolérance pharmacologique à la fois pour l’efficacité et certains effets indésirables des benzodiazépines, qui diminuent de façon marquée dès les premières semaines de traitement. Le principal corollaire de cette tolérance est la survenue d’un syndrome d’interruption à l’arrêt du traitement, parfois sévère et douloureux.
Dans la lutte contre les traitements à long terme, il apparaît pertinent de cibler la primo-prescription de benzodiazépines : il est essentiel de limiter à la fois les indications et la durée des traitements dès leur initiation.
Les co-addictions aux benzodiazépines sont fréquentes chez les patients en soins pour une addiction à l’alcool ou aux drogues illicites, avec des complications plus fréquentes, notamment surdoses et tentatives de suicide.
La prescription des benzodiazépines reste essentielle dans la prévention des complications de sevrage de l’alcool et des benzodiazépines elles-même chez les patients traités pour un trouble lié à l'usage de substances, mais une durée de prescription limitée et des modalités de délivrance contrôlées sont utiles dans les soins de cette population spécifique.
Points essentiels
Sept études évaluaient des stratégies pharmacologiques et 12 des interventions non pharmacologiques : psychothérapies ou interventions minimales pour l’arrêt des benzodiazépines.
Parmi les interventions pharmacologiques, seule la mélatonine est efficace chez les patients présentant des insomnies isolées.
Les psychothérapies comportementales et cognitives sont efficaces pour augmenter le sentiment d’efficacité personnelle et en cas de troubles du sommeil.
Les interventions minimales en direction des médecins prescripteurs et des patients sont remarquablement coût-efficaces.
Aucune étude n’évalue spécifiquement les patients utilisant de fortes doses de benzodiazépines ou présentant des morbidités addictives, psychiatriques ou médicales.
All long term benzodiazepine users in one inner London general practice were asked to participate in a study of their attitudes to their drugs. The 64 respondents had mixed views about benzodiazepines and did not conform to the stereotype presented in the media. Although 58% of the sample had attempted to stop taking benzodiazepines, this was usually not until at least one year of taking the drug. At the time of interview, 50% of the sample expressed a desire to stop taking their tablets. However, the majority were uncertain whether their general practitioner wished them to continue taking the drugs or not. It is argued that users' views of their medication must be taken into account in the debate about tranquillizer dependence.
As there is no multidimensional instrument available that reflects the severity of benzodiazepine (BZD) dependence comprehensively, the Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ) was developed and investigated. The Bendep-SRQ, Symptom Checklist-90 (SCL-90), Schedules for Clinical Assessments in Neuropsychiatry (SCAN), and Addiction Severity Index-Revised (ASI-R) were administered to 115 general practice (GP) patients, 124 psychiatric outpatients, and 33 self-help patients who were using BZDs. Factor and Rasch analyses were applied to construct scales. Reliability assessments were made in terms of subject discriminability, item discriminability, and test-retest stability. To support the construct validity of the scales, theoretical rationales were required to explain the specific item order provided by the Rasch scale values. To assess the concurrent and discriminant validity, a matrix consisting of the above-mentioned measures was factor-analyzed. Four Rasch-homogeneous scales were delineated: problematic use, preoccupation, lack of compliance, and withdrawal. Nearly all subject discriminability, item discriminability, and test-retest results indicated good reliability. A BZD dependence factor was extracted with high loadings for the Bendep-SRQ scales and the concurrent measures. The discriminant measures had high loadings on other factors. The scalability, reliability, and validity of the Bendep-SRQ scales appeared to be good. The Bendep-SRQ shows great promise as a useful and easily manageable instrument for assessment of the severity of BZD dependence in clinical practice and scientific research.
Benzodiazepine use by elderly patients is associated with adverse outcomes including increased risk of falls and fractures, motor vehicle accidents and cognitive impairment. Recent studies suggest that individualized feedback and education to physicians may improve drug prescribing. In this study, we evaluated an intervention to address the inappropriate prescribing of benzodiazepines for elderly patients.
We identified 1624 primary care physicians who wrote at least 10 prescriptions for the target drugs in a 2-month period and randomly assigned these physicians to the intervention group or the control group. We obtained data from the Ontario Drug Benefit claims database, which covers all Ontario residents aged 65 years and over for drugs selected from a minimally restrictive formulary. Every 2 months for 6 months, confidential profiles of benzodiazepine prescription use coupled with evidence-based educational bulletins were mailed to the intervention group. The control group received feedback and educational bulletins about first-line antihypertension drug prescribing for elderly patients. Our main outcome measures were reductions in the proportion of each physician's total benzodiazepine prescriptions for long-acting agents, combinations of benzodiazepines with other psychoactive medications (including other benzodiazepines) and long-term benzodiazepine therapy.
After randomization, 168 physicians agreed to be in the intervention group and 206 in the control group. Their demographic and prescribing characteristics were similar. Although the proportion of long-acting benzodiazepine prescriptions decreased by 0.7% in the intervention group between the baseline period and the end of the intervention period (from 20.3%, or a mean of 29.5 prescriptions, to 19.6%, or a mean of 27.7 prescriptions) and increased by 1.1% in the control group (from 19.8%, or a mean of 26.4 prescriptions, to 20.9%, or a mean of 27.7 prescriptions) (p = 0.036), this difference was not clinically significant. There was no significant difference over the study period in either combination prescribing of benzodiazepines or in prescriptions for long-term benzodiazepine therapy.
We did not find that a program of confidential feedback and educational material offered to Ontario primary care physicians had a clinically significant impact on their benzodiazepine prescribing.
Older adults are the main recipients of repeat prescriptions for benzodiazepine (BZD) hypnotics. BZDs can impair cognitive function and may not aid sleep when taken continuously for years. This study therefore aimed to determine if withdrawing from BZDs leads to changes in patients' cognitive function, quality of life, mood and sleep.
One hundred and ninety-two long-term users of BZD hypnotics, aged > or = 65 years, were identified in 25 general practices. One hundred and four who wished to withdraw were randomly allocated to one of two groups under double-blind, placebo controlled conditions: group A's BZD dose was tapered from week 1 of the trial; group B were given their usual dose for 12 weeks and then it was tapered. An additional group (C) of 35 patients who did not wish to withdraw from BZDs participated as 'continuers'. All patients were assessed at 0, 12 and 24 weeks and 50% were reassessed at 52 weeks.
Sixty per cent of patients had taken BZDs continuously for > 10 years; 27% for > 20 years. Of all patients beginning the trial, 80% had successfully withdrawn 6 months later. There was little difference between groups A and B, but these groups differed from continuers (C) in that the performance of the withdrawers on several cognitive/psychomotor tasks showed relative improvements at 24 or 52 weeks. Withdrawers and continuers did not differ in sleep or BZD withdrawal symptoms.
These results have clear implications for clinical practice. Withdrawal from BZDs produces some subtle cognitive advantages for older people, yet little in the way of withdrawal symptoms or emergent sleep difficulties. These findings also suggest that, taken long-term, BZDs do not aid sleep.
Long-term use of hypnotics is not recommended because of risks of dependency and adverse effects on health. The usual clinical management of benzodiazepine dependency is gradual tapering, but when used alone this method is not highly effective in achieving long-term discontinuation. We compared the efficacy of tapering plus cognitive-behavioural therapy for insomnia with tapering alone in reducing the use of hypnotics by older adults with insomnia.
People with chronic insomnia who had been taking a benzodiazepine every night for more than 3 months were recruited through media advertisements or were referred by their family doctors. They were randomly assigned to undergo either cognitive-behavioural therapy plus gradual tapering of the drug (combined treatment) or gradual tapering only. The cognitive-behavioural therapy was provided by a psychologist in 8 weekly small-group sessions. The tapering was supervised by a physician, who met weekly with each participant over an 8-week period. The main outcome measure was benzodiazepine discontinuation, confirmed by blood screening performed at each of 3 measurement points (immediately after completion of treatment and at 3- and 12-month follow-ups).
Of the 344 potential participants, 65 (mean age 67.4 years) met the inclusion criteria and entered the study. The 2 study groups (35 subjects in the combined treatment group and 30 in the tapering group) were similar in terms of demographic characteristics, duration of insomnia and hypnotic dosage. Immediately after completion of treatment, a greater proportion of patients in the combined treatment group had withdrawn from benzodiazepine use completely (77% [26/34] v. 38% [11/29]; odds ratio [OR] 5.3, 95% confidence interval [CI] 1.8-16.2; OR after adjustment for initial benzodiazepine daily dose 7.9, 95% CI 2.4-30.9). At the 12-month follow-up, the favourable outcome persisted (70% [23/33] v. 24% [7/29]; OR 7.2, 95% CI 2.4-23.7; adjusted OR 7.6, 95% CI 2.5-26.6); similar results were obtained at 3 months.
A combination of cognitive-behavioural therapy and benzodiazepine tapering was superior to tapering alone in the management of patients with insomnia and chronic benzodiazepine use. The beneficial effects were sustained for up to 1 year. Applying this multidisciplinary approach in the community could help reduce benzodiazepine use by older people.
This study evaluated the effectiveness of a supervised benzodiazepine taper, singly and combined with cognitive behavior therapy, for benzodiazepine discontinuation in older adults with chronic insomnia.
Seventy-six older adult outpatients (38 women, 38 men; mean age of 62.5 years) with chronic insomnia and prolonged use (mean duration of 19.3 years) of benzodiazepine medication for sleep were randomly assigned for a 10-week intervention consisting of a supervised benzodiazepine withdrawal program (N=25), cognitive behavior therapy for insomnia (N=24), or supervised withdrawal plus cognitive behavior therapy (N=27). Follow-up assessments were conducted at 3 and 12 months. The main outcome measures were benzodiazepine use, sleep parameters, and anxiety and depressive symptoms.
All three interventions produced significant reductions in both the quantity (90% reduction) and frequency (80% reduction) of benzodiazepine use, and 63% of the patients were drug-free within an average of 7 weeks. More patients who received medication taper plus cognitive behavior therapy (85%) were benzodiazepine-free after the initial intervention, compared to those who received medication taper alone (48%) and cognitive behavior therapy alone (54%). The patients in the two groups that received cognitive behavior therapy perceived greater subjective sleep improvements than those who received medication taper alone. Polysomnographic data showed an increase in the amount of time spent in stages 3 and 4 sleep and REM sleep and a decrease in total sleep time across all three conditions from baseline to posttreatment. Initial benzodiazepine reductions were well maintained up to the 12-month follow-up, and sleep improvements became more noticeable over this period. No significant withdrawal symptoms or adverse events were associated with benzodiazepine tapering.
A structured, time-limited intervention is effective in assisting chronic users of benzodiazepine medication to discontinue or reduce their use of medication. The addition of cognitive behavior therapy alleviates insomnia, but sleep improvements may become noticeable only after several months of benzodiazepine abstinence.
Better understanding of compliance with BZD taper is warranted. Compliance with a taper program and perceived self-efficacy (SE) in being able to comply with hypnotic reduction goals was monitored weekly in 52 older adults (mean age: 63.0 years) with chronic insomnia (average duration: 21.9 years) who underwent a 10-week physician-supervised medication tapering. One group received cognitive- behavior therapy for insomnia during discontinuation, whereas the other did not. Compliant patients showed higher SE ratings at Weeks 6, 8, 9, and 10. Medication-free patients at the end of the treatment also reported higher mean SE ratings at those 4 weeks. Differences remained significant when withdrawal symptoms and sleep efficiency were controlled for. These results have important clinical implications because SE may indicate key time points when patients are experiencing more difficulty during discontinuation.
To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial.
We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in general practice.
Of 180 patients, we completed follow-up for 170 (94%). Of these, 50 (29%) achieved long-term success, defined as no use of benzodiazepines during follow-up. Independent predictors of success were as follows: offering a taper-off program with group therapy (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.5 to 3.9) or without group therapy (HR 2.9; 95% CI, 1.8 to 4.8); a lower daily benzodiazepine dosage at the start of tapering off (HR 1.5; 95% CI, 1.2 to 1.9); a substantial dosage reduction by patients themselves just before the start of tapering off (HR 2.1; 95% CI, 1.4 to 3.3); less severe benzodiazepine dependence, as measured by the Benzodiazepine Dependence Self-Report Questionnaire Lack of Compliance subscale (HR 2.4; 95%CI, 1.1 to 5.2); and no use of alcohol (HR 1.7; 95% CI, 1.2 to 2.5). Patients who used over 10 mg of diazepam equivalent, who had a score of 3 or more on the Lack of Compliance subscale, or who drank more than 2 units of alcohol daily failed to achieve long-term abstinence.
Benzodiazepine dependence severity affects long-term taper outcome independent of treatment modality, benzodiazepine dosage, psychopathology, and personality characteristics. An identifiable subgroup needs referral to specialized care.
This study evaluated the specific effectiveness of cognitive-behavior therapy (CBT) combined with medication tapering for benzodiazepine discontinuation among generalized anxiety disorder (GAD) patients by using a nonspecific therapy control group. Sixty-one patients who had used benzodiazepines for more than 12 months were randomly assigned to the experimental conditions. Nearly 75% of patients in the CBT condition completely ceased benzodiazepine intake, as compared with 37% in the control condition. Results of the 3-, 6-, and 12-month follow-ups confirmed the maintenance of complete cessation. Discontinuation rates remained twice as high in the CBT condition. The number of patients who no longer met GAD criteria was also greater in the CBT condition. The addition of specific CBT components thus seemed to facilitate benzodiazepine tapering among patients with GAD.
The long-term use of benzodiazepines is highly prevalent in developed societies and is not devoid of risks. Withdrawing patients from these drugs is often difficult. Tapering off benzodiazepines has been shown to be a good strategy for discontinuing their long-term use.
To establish the efficacy of an intervention programme for reducing the chronic use of benzodiazepines.
Randomised, two-arm, parallel, non-blinded controlled trial.
Three urban healthcare centres covering a population of 50,000 inhabitants (Mallorca, Spain).
Adult patients (n = 139) taking benzodiazepines daily for more than a year and visited by their family physician were randomised into an intervention group (n = 73) that received standardised advice and a tapering off schedule with biweekly follow-up visits, or into a control group (n = 66), that was managed following routine clinical practice. Both were followed for a year.
Patients achieved withdrawal or reduced their dose by at least 50% after 6 and 12 months. Abstinence and withdrawal symptoms were also measured. Both groups were homogeneous for personal, clinical and psychological characteristics and for benzodiazepine use. Only two patients from each group were lost to follow-up. After 12 months, 33 (45.2%) patients in the intervention group and six (9.1%) in the control group had discontinued benzodiazepine use; relative risk = 4.97 (95% confidence interval [CI] = 2.2 to 11.1), absolute risk reduction = 0.36 (95% CI = 0.22 to 0.50). For every three interventions, one patient achieved withdrawal. Sixteen (21.9%) subjects from the intervention group and 11 (16.7%) controls reduced their initial dose by more than 50%.
Standardised advice given by the family physician, together with a tapering off schedule, is effective for withdrawing patients from long-term benzodiazepine use and is feasible in primary care.
There is a continued high prevalence of benzodiazepine use by older community-residing adults and of their continued prescription by practitioners, despite well known adverse effects and the availability of safer, effective alternatives.
To understand factors influencing chronic use of benzodiazepines in older adults.
Qualitative study, semistructured interviews with physicians.
Thirty-three practicing primary care physicians around Philadelphia.
Qualitative interviews were audiotaped, transcribed, and entered into a qualitative software program. A multidisciplinary team coded transcripts and developed themes.
Physicians generally endorsed benzodiazepines as effective treatment for anxiety, citing quick action and strong patient satisfaction. The use of benzodiazepines in older adults was not seen to be problematic because they did not show drug-seeking or escalating dose behavior suggesting addiction. Physicians minimized other risks of benzodiazepines and did not view monitoring or restricting renewal of prescriptions as an important clinical focus relative to higher-priority medical issues. Many physicians expressed skepticism about risks of continued use and considerable pessimism in the successful taper/discontinuation in older patients with long-term use and prior failed attempts. Physicians also anticipated patient resistance to any such efforts, including switching physicians.
Primary care physicians are averse to addressing the public health problem of benzodiazepine overuse in the elderly. Their attitudes generally conflict with practice guidelines and they complain of a lack of training in constructive strategies to address this problem. A 2-pronged effort should focus on increasing skill level and preventing new cases of benzodiazepine dependency through improved patient education and vigilant monitoring of prescription renewal.
Objective: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. Method: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in general practice. Results: Of 180 patients, we completed follow-up for 170 (94%). Of these, 50 (29%) achieved long-term success, defined as no use of benzodiazepines during follow-up. Independent predictors of success were as follows: offering a taper-off program with group therapy (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.5 to 3.9) or without group therapy (HR 2.9; 95%CI, 1.8 to 4.8); a lower daily benzodiazepine dosage at the start of tapering off (HR 1.5; 95%CI, 1.2 to 1.9); a substantial dosage reduction by patients themselves just before the start of tapering off (HR 2.1; 95%CI, 1.4 to 3.3); less severe benzodiazepine dependence, as measured by the Benzodiazepine Dependence Self-Report Questionnaire Lack of Compliance subscale (HR 2.4; 95%CI, 1.1 to 5.2); and no use of alcohol (HR 1.7; 95%CI, 1.2 to 2.5). Patients who used over 10 mg of diazepam equivalent, who had a score of 3 or more on the Lack of Compliance subscale, or who drank more than 2 units of alcohol daily failed to achieve long-term abstinence. Conclusions: Benzodiazepine dependence severity affects long-term taper outcome independent of treatment modality, benzodiazepine dosage, psychopathology, and personality characteristics. An identifiable subgroup needs referral to specialized care.
• We compared the effect on withdrawal severity and acute outcome of a 25% per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients. Patients unable to tolerate taper were permitted to slow the taper rate. Ninety percent of patients experienced a withdrawal reaction, but it was rarely more than mild to moderate. Nonetheless, 32% of long half-life and 42% of short half-life benzodiazepinetreated patients were unable to achieve a drug-free state. The most difficulty was experienced in the last half of taper. Baseline personality, high Eysenck neuroticism, female sex, and mild-tomoderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life. These findings suggest that personality factors contribute significantly to the patient's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines.
Potentially inappropriate medications (PIMs) continue to be prescribed and used as first-line treatment for the most vulnerable of older adults, despite evidence of poor outcomes from the use of PIMs in older adults. PIMs now form an integral part of policy and practice and are incorporated into several quality measures. The specific aim of this project was to update the previous Beers Criteria using a comprehensive, systematic review and grading of the evidence on drug-related problems and adverse drug events (ADEs) in older adults. This was accomplished through the support of The American Geriatrics Society (AGS) and the work of an interdisciplinary panel of 11 experts in geriatric care and pharmacotherapy who applied a modified Delphi method to the systematic review and grading to reach consensus on the updated 2012 AGS Beers Criteria. Fifty-three medications or medication classes encompass the final updated Criteria, which are divided into three categories: potentially inappropriate medications and classes to avoid in older adults, potentially inappropriate medications and classes to avoid in older adults with certain diseases and syndromes that the drugs listed can exacerbate, and finally medications to be used with caution in older adults. This update has much strength, including the use of an evidence-based approach using the Institute of Medicine standards and the development of a partnership to regularly update the Criteria. Thoughtful application of the Criteria will allow for (a) closer monitoring of drug use, (b) application of real-time e-prescribing and interventions to decrease ADEs in older adults, and (c) better patient outcomes.
SYSNOPSIS
Thirty drug-free patients suffering from chronic anxiety states were compared with 30 normal controls matched for age, sex, and social class on a variety of physiological and psychological measures. The tests included the electroencephalogram, the auditory evoked response, and skin conductance recorded during a passive and an active condition and auditory reaction time, the digit symbol substitution test, and arithmetic. The patients showed increased EEG voltage, shorter latencies of the evoked response, higher skin conductance levels, higher pulse rate and less pupillary constriction, and they responded less to the increase in activation. They also showed impairment on complex psychological tests. It is concluded that pathological anxiety involves an increase in arousal irrelevant to the task and has a disorganizing rather than a facilitating effect on performance.
Rationale, aims and objectives Insomnia and sleep problems are common with many sufferers seeking medical help from general practitioners (GPs) whose clinical response is limited, often involving prescription of hypnotic drugs. The case for improving the quality of care for patients with insomnia is compelling but there is little evidence about how better care could be achieved in a primary care setting. The aim of this study was to investigate GPs' management preferences for sleep problems and their awareness and perception of opportunities for improving care as well as reducing the use of benzodiazepines and Z drugs.
Methods Cross-sectional survey of GPs using a self-administered postal questionnaire in 2005 to all GPs in West Lincolnshire Primary Care Trust Lincolnshire, UK.
Results A total of 84 of 107 (78.5%) questionnaires sent to GP principals were returned after one reminder. Respondents favoured Z drugs over benzodiazepines for the majority of indications. Respondent attitudes to benzodiazepines and Z drugs were generally negative whereas they were positive towards initiatives to reduce hypnotic prescribing through personal guidance, awareness-raising strategies and organizational interventions.
Conclusions GPs were negative in attitude towards hypnotics and positive towards reducing prescribing for sleep problems. They need to develop resources and better strategies for assessment and non-pharmacological management of patients presenting with insomnia for the first time as well as those on long-term hypnotics. The feasibility and effectiveness of psychosocial interventions tailored to patient and service needs in primary care setting should be evaluated systematically seeking to understand potential clinical benefits as well as potential undesirable effects of service changes.
To evaluate the effect of the Medicare benzodiazepine coverage exclusion on psychotropic use of benzodiazepine users.
Pre-post design with concurrent control group.
General community.
Intervention and comparison cohorts of individuals drawn from the same insurer who were prescribed benzodiazepines through the end of 2005. Intervention participants (n = 19,339) were elderly adults from a large, national Medicare Advantage plan subject to benzodiazepine exclusion as a result of the Medicare Modernization Act (MMA). Comparison participants (n = 3,488) were near-elderly individuals enrolled in a managed care plan not subject to the MMA benzodiazepine exclusion.
Any psychotropic drug use and expenditures.
In the intervention cohort, benzodiazepine use and expenditures significantly declined from 100% and 59, respectively, in 2007. Nonbenzodiazepine psychotropic drug use and expenditures significantly increased from 35.8% and 207, respectively, in 2007. In the comparison cohort, benzodiazepine use and expenditures also significantly declined from 100% and 105, respectively, in 2007, but nonbenzodiazepine psychotropic drug use and expenditures significantly declined from 55.4% and 572, respectively, in 2007. Changes in antidepressant and anxiolytic use were the primary cause of changes in nonbenzodiazepine psychotropic drugs in both cohorts.
Use of benzodiazepines continued in elderly adults despite negative financial incentives, possibly because of the low costs of such medications. Although some substitution occurred with antidepressants and anxiolytics, the magnitude of this increase did not fully offset the reduction in benzodiazepine use.
In two Danish general practices a few simple rules applicable to all age groups were introduced in order to reduce consumption of benzodiazepines (BZ) and cyclopyrrolones (CP). These rules, termed the "Thyborøn-Model", included the termination of telephone prescriptions, the issuance of prescriptions only following personal consultation and the restriction of prescriptions to a maximum of a single month's consumption. The purpose of the present demographic analysis is to investigate whether the intervention was successful for the elderly, who are considered to be a special target group. The findings presented here reveal that the number of BZ and CP users increased with increasing age. Furthermore, the results indicate that the intervention was effective in reducing the consumption of BZ and CP for middle-aged and elderly patients, and that there is a significantly better effect of this model for middle-aged than for elderly patients. These findings constitute the first demographic evaluation of the effects of the "Thyborøn-Model" with focus on the special target group of elderly patients, and indicate that it is advisable to introduce these simple rules for all age groups, especially since they also are effective on elderly patients.
High-potency benzodiazepines, such as clonazepam, are frequently used in the treatment of panic disorder (PD) because of their rapid onset of action and good tolerability. However, there is concern about their potential to cause withdrawal symptoms. We aimed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years. A specific scale for judging withdrawal was also developed, the Composite Benzodiazepine Discontinuation Symptom Scale. We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication. The trial consisted of a 4-month period of tapering and an 8-month follow-up period. The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached, followed by a decrease of 0.25 mg per week. The mean dosage at the start of tapering was 2.7 +/- 1.2 mg/d. In total, 51 (68.9%) of the patients were free of the medication after the 4 months of tapering according to the protocol, and 19 (26.0%) of the patients needed another 3 months to be free of medication. Clonazepam discontinuation symptoms were mostly mild and included mainly: anxiety, shaking/trembling/tremor, nausea/vomiting, insomnia/nightmares, excessive sweating, tachycardia/palpitations, headache, weakness, and muscle aches. The improvement in PD and general well-being was maintained during both the taper and follow-up phases. Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually. We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk.
A self-report questionnaire is described which records the main symptoms experienced during withdrawal from benzodiazepines in pharmacologically dependent patients. The questionnaire consists of 20 items; evidence is given that these are reasonably independent and are sensitive in detecting withdrawal symptoms from a study of 68 patients undergoing slow withdrawal from benzodiazepines.
A multicenter, double-blind, placebo-controlled study was conducted to determine the safety of concurrently using buspirone with alprazolam before and during a gradual tapering of the alprazolam dose. Thirty-six patients received placebo t.i.d. and 36 received buspirone 5 mg. t.i.d. Findings included significantly greater anxiety (as measured by the Hamilton Rating Scale for Anxiety) in the placebo group and significantly reduced manifestations of abstinence (as measured by the Abstinence Rating Scale) in the buspirone group. Buspirone and alprazolam may be used together safely, and buspirone may be started early in the alprazolam tapering process.
We compared the effect on withdrawal severity and acute outcome of a 25% per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients. Patients unable to tolerate taper were permitted to slow the taper rate. Ninety percent of patients experienced a withdrawal reaction, but it was rarely more than mild to moderate. Nonetheless, 32% of long half-life and 42% of short half-life benzodiazepine-treated patients were unable to achieve a drug-free state. The most difficulty was experienced in the last half of taper. Baseline personality, high Eysenck neuroticism, female sex, and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life. These findings suggest that personality factors contribute significantly to the patient's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines.
The aim of the study was to monitor discontinuation of benzodiazepine prescribing among patients who were either first-time or long-term users. The study was carried out as a one-year follow-up study in general practice in the County of Arhus, Denmark. In all, 201 patients with first-time prescriptions and 607 patients with long-term prescriptions participated, and in the one-year follow-up period 55% and 12%, respectively, stopped having further prescriptions of benzodiazepines or other psychotropic drugs. Older first-time users continued significantly more often than younger. In an age and sex-stratified analysis, users of benzodiazepine hypnotics/sedatives continued significantly more often than users of benzodizepine tranquillizers among first-time users (odds ratio (OR) 2.15) as well as long-term users (OR: 2.16). Continuation of long-term use was significantly correlated with the female sex (OR: 1.71), living alone (OR: 1.97), daily use (OR: 4.17), high amounts of defined daily doses (DDD) per prescription, and a high ratio between prescribed daily dose and DDD.
The objective, sensitive, and reliable quantitation of withdrawal symptoms is essential to assess physical dependence on drugs. Data collected from 23 patients abusing high doses of benzodiazepines (mean diazepam dose equivalents, 150 mg/day; range, 40-500) and from 40 long-term therapeutic users randomized to receive either placebo (N = 19) or diazepam (N = 21; mean diazepam dose equivalents, 15 mg/day; range, 5-40; mean duration of use, 72 months; range, 6-240) were analyzed. Information on the type and severity of symptoms was obtained from several assessment instruments. In the high-dose abuse group, plasma benzodiazepine concentrations were measured daily and the 3 consecutive days of greatest relative daily fall were considered the critical withdrawal period. Selection of the 22 items of the Clinical Institute Withdrawal Assessment-Benzodiazepines (CIWA-B) was based on statistically significant differences between baseline and critical withdrawal periods in high-dose subjects and between symptoms associated with placebo and diazepam in low-dose subjects, using contingency tables and logistic regression analysis. Of the 104 symptoms measured by the assessment instruments, 22 symptoms were found to distinguish withdrawal from prewithdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
In a general population survey by Gallup in Great Britain of 4148 subjects, 7.7% had taken benzodiazepines within the last year (male:female ratio 106:212). Younger subjects tended to take anxiolytics for shorter periods compared with older subjects, who often took hypnotics chronically. This pattern was most marked among females. Dosage escalation, tolerance, high daily dose usage, and hoarding were not common. A substantial proportion of current users had experienced difficulty in stopping their medication. Withdrawal problems were associated with being older than 45 years and consuming benzodiazepines for over 12 months. This lends support to the idea of benzodiazepine dependency. However, the appropriateness of long-term therapy for chronic symptoms cannot be ruled out.
Severity of withdrawal symptoms and clinical outcome were compared in 19 elderly and 22 younger benzodiazepine-dependent patients matched for benzodiazepine half-life, dosage, and duration of treatment. During gradual taper of benzodiazepine doses, the elderly patients showed significantly less severe withdrawal symptoms on several clinical measures and a comparably favorable outcome. Approximately half of each group remained benzodiazepine free for at least 4 weeks. Both groups of patients tolerated drug discontinuation without serious consequences such as seizures or psychosis. Tapered benzodiazepine withdrawal did not appear to be more risky for the elderly group than for the younger patients.
We conducted a double-blind, placebo-controlled trail in which 40 patients who had undergone long-term therapy with benzodiazepines were switched to placebo or to diazepam in a dose approximately equivalent to their usual dose of the benzodiazepine; the dose of diazepam was then tapered during an eight-week period. Patients were assessed clinically and psychologically and had weekly sessions of behavioral therapy. The subjects who received placebo had more symptoms, assessed their symptoms as more severe, and stopped taking the study drug at a higher rate than those receiving the tapering doses of diazepam. The subjects in the placebo group also had symptoms shortly after being switched to placebo, whereas those in the diazepam group had symptoms much later. Some withdrawal symptoms were distinct from those of anxiety (e.g., tinnitus, involuntary movement, and perceptual changes). Withdrawal symptoms occurred earlier in patients who had received short-acting benzodiazepines than in those who had received long-acting benzodiazepines. Symptoms gradually disappeared over a four-week period in both the placebo and the diazepam groups. Serial determination of plasma benzodiazepine concentrations was a useful way to assess compliance, treatment outcome, and relapse during withdrawal. We conclude that a clinically important, mild, but distinct withdrawal syndrome occurs after discontinuation of long-term therapeutic use of benzodiazepines.
This report describes the historical evolution, development, rationale and validation of the Hopkins Symptom Checklist (HSCL), a self-report symptom inventory. The HSCL is comprised of 58 items which are representative of the symptom configurations commonly observed among outpatients. It is scored on five underlying symptom dimensions—sommatization, obsessive-compulsive, interpersonal sensitivity, anxiety and depression—which have been identified in repeated factor analyses. A series of studies have established the factorial invariance of the primary symptom dimensions, and substantial evidence is given in support of their construct validity. Normative data in terms of both discrete symptoms and primary symptom dimensions are presented on 2,500 subjects—1,800 psychiatric outpatients and 700 normals. Indices of pathology reflect both intensity of distress and prevalence of symptoms in the normative samples. Standard indices of scale reliability are presented, and a broad range of criterion-related validity studies, in particular an important series reflecting sensitivity to treatment with psychotherapeutic drugs, are reviewed and discussed.
A study of benzodiazepine prescribing in a single-handed general practice was carried out over a period of three months. It seemed that the existing pattern of prescribing was indiscriminate and ineffective, and that repeat prescriptions were poorly controlled. A programme of controlled withdrawal was instituted for patients whose consumption of benzodiazepines was felt to be no longer appropriate. Of 103 patients identified who had been taking benzodiazepines for longer than three months, 78 were entered into the programme. On completion, 45 patients (58 per cent) had discontinued benzodiazepines completely, and a further 13 (17 per cent) were taking less than half their original dose. Four patients had failed to reduce consumption at all and two were lost to follow-up. At follow-up between three and five months later, 49 patients (63 per cent) had discontinued benzodiazepines completely and only two had restarted treatment. The median time taken to complete the programme was 3.2 weeks, with 95 per cent of patients completing within six weeks. Withdrawal was generally well tolerated, with a temporary increase in insomnia as the main symptom. Two patients experienced severe symptoms, but both had stopped treatment abruptly.
41 outpatients who were long-term consumers of diazepam in therapeutic dosage were gradually withdrawn from the drug over 3 months by stepwise reduction. In a double-blind procedure half the patients began withdrawal immediately and half after 8 weeks. Of 36 patients who completed treatment, 16 (44.4%) experienced true withdrawal phenomena on reducing their drugs, but 8 other patients had pseudo-withdrawal reactions at a time when their drug treatment was unchanged. The pseudo-withdrawal reactions consisted of an increase in anxiety symptoms only, whereas true withdrawal symptoms also included perceptual changes and psychotic symptoms. Examination of pharmacological and clinical predictors of withdrawal phenomena and later relapse showed that personality factors were the most important, patients with passive-dependent traits having a significantly greater prevalence of withdrawal reactions.
From a sample of 257 elderly patients, 93 subjects who had received benzodiazepine (mainly diazepam) prescriptions for one or more years were interviewed about their subjective perception of the drug's effects and their attitudes regarding its use. The subjects were predominantly women: mean age was 72 years. All subjects had begun use of benzodiazepine more than two years earlier, although some had since stopped using the drug; more than a third had used it for more than six years. About half of the subjects said they took no more of the drug than had been initially prescribed, and three quarters reported they took the medications only when a need was felt. The principal indication for use of benzodiazepines was described as tension. Those who were still taking the drug at the time of interview were more likely to live alone and to say that they had the same problems as when they began its use. None of the subjects who had discontinued use of the drugs had been aware of withdrawal symptoms, and there was no evidence that any subject had become addicted, although several expressed a fear of this. It appears that in this age group, prolonged use of benzodiazepine at low doses, with the patients regulating the quantity, is safe and may be helpful. Most subjects, even if not helped, always kept some of the drug at home in case they might need it.
Since recent research has suggested that the major metabolites of progesterone are barbiturate-like modulators of GABAergic function, we undertook a pilot study of the efficacy of micronized progesterone in attenuating withdrawal and facilitating discontinuation in benzodiazepine-dependent patients with a minimum of 1 year of continuous daily use. Forty-three patients taking a mean daily dose of 16.2 mg of diazepam (or its equivalent) were assigned, doubleblind, to treatment with either placebo (n = 13) or progesterone (n = 30). Progesterone was titrated to a mean daily dose of 1983 mg, and was co-administered for 3 weeks, after which the benzodiazepine was tapered by 25% per week. Progesterone (or placebo) was then continued for 4 weeks before being discontinued. There was no progesterone versus placebo difference in the severity of taper withdrawal. Withdrawal checklist change scores were 17.3 for progesterone and 16.5 for placebo (F 0.63; df 2.31; n.s.), and the Hamilton rating scale for anxiety change scores were 7.8 for progesterone and 6.3 for placebo (F 0.22; df 2.30; n.s.). There was no difference in ability to remain drug-free at 12 weeks post-taper, with 57% of progesterone-treated patients, and 58% of placebo-treated patients having a successful outcome.
On 1 January 1989, in an effort to reduce diversion of benzodiazepines for illicit use and reduce inappropriate prescribing, a regulation was implemented requiring the reporting of all benzodiazepine prescriptions to the New York State Department of Health. To assess the impact of the regulation on prescribing practices to the elderly, we followed the number of benzodiazepines and other central nervous system medications prescribed to a cohort of participants in an elderly pharmaceutical insurance program. Benzodiazepines were prescribed for 4652 (22%) of the 20,944 patients studied. By the last quarter of 1989, benzodiazepines were prescribed for 3120 (15%) patients, a decrease of 33%. The number of prescriptions of benzodiazepines decreased by 5010 (45%), from 11,123 to 6113. Decreases in the number of prescriptions were similar across benzodiazepine brands (range 40-56%). Statistically significant (p < 0.05) decreases were seen in all sex, age, race and marital status groups. Increases in number (and percent increases) of prescriptions for miscellaneous anxiolytics (i.e. hydroxyzine (399, 69%), meprobamate (299, 149%), buspirone (263, 111%), chloral hydrate (138, 265%), antidepressants (658, 19%), barbiturates (150, 29%), and tranquilizers (198, 19%), some of which may be more toxic or less effective, were noted. New York State's reporting regulation was effective in reducing both the number of patients being prescribed benzodiazepines and the number of prescriptions given to those who remain on benzodiazepines in the elderly population studies.
Long-term low-dosage dependence on benzodiazepines in traditionally explained by withdrawal symptoms. Previous research has not given much attention to reports that suggest that many patients oppose stopping benzodiazepines long before withdrawal symptoms have developed. This study investigates the scope of and factors associated with this pre-withdrawal treatment insistence.
Patients receiving long-term low-dosage benzodiazepines in primary care were asked to take a drug-holiday of at least 3 weeks. Sociodemographic, medication, morbidity and attitudinal variables were assessed in addition to the GPs' perceptions of their patients.
Two-thirds of the patients rejected the drug-holiday proposal. Patients who refused a drug-holiday were less educated and were using a higher percentage of long-acting benzodiazepines than patients who accepted the drug-holiday proposal. Those who refused were seen by their GPs as being more complaining, harder to satisfy and less co-operative.
These results provide evidence for drug-seeking or craving behaviour of patients who receive low-dosage benzodiazepine prescriptions. A major problem in benzodiazepine withdrawal occurs before the withdrawal programme has even begun. These data show that benzodiazepine low-dosage dependence should be considered a real form of dependence.
Personality psychopathology exerts a significant and independent effect on the course of benzodiazepine (BZ) discontinuation, worsening the subjective severity of withdrawal symptoms and significantly increasing the occurrence of early taper failures.
One hundred and seventy-one patients participating in a BZ discontinuation programme were administered several personality measures prior to taper. Patients were stabilized for 3 weeks at their baseline BZ dosage and then tapered off 25% per week over 4 weeks, with the option to extend up to 6 weeks if necessary.
High levels of passivity and dependency as assessed by the MMPI Dependence subcluster, and at a trend level high Eysenck Neuroticism and high TPQ Harm Avoidance contributed significantly to the prediction of benzodiazepine withdrawal severity. Though there was a high correlation between personality measures, psychopathology and adjusted BZ dose, the effects of personality on withdrawal severity was significant, particularly in the initial phases of BZ taper, when taper severity was still relatively mild.
These findings indicate that clinical decisions on how to manage BZ tapering should be guided by personality assessments, in addition to the usual considerations of BZ dosage, residual psychopathology, duration of treatment, etc. The potential for difficulty with discontinuation related to personality traits should be one of the factors weighted in the risk-benefit assessment made in the planning of benzodiazepine treatment for patients with anxious symptomatology.
Recent uncontrolled research suggested that trazodone and sodium valproate may be helpful in benzodiazepine (BZ) discontinuation. We therefore undertook a double-blind study to assess whether trazodone and valproate, as compared to placebo, would attenuate withdrawal and facilitate discontinuation in BZ-dependent patients with a minimum of 1 year daily BZ use. Seventy-eight patients, taking a mean dose of 19+/-17 mg/day of diazepam (or its equivalent), were stabilized for several weeks on their BZ (16 diazepam, 25 lorazepam, 37 alprazolam) and then for 1-2 weeks, pretreated with trazodone, sodium valproate or placebo before being tapered at 25% per week. All treatments were continued for 5 weeks post-taper. BZ-free status was assessed after 5 and 12 weeks post-taper. Neither trazodone nor valproate had any significant effect on withdrawal severity. Peak physician withdrawal checklist change from baseline to peak severity was 16.4 for trazodone, 18.04 sodium valproate and 18.24 placebo (F = 0.10; NS). Taper success rates were significantly effected by both active agents at the 5-week, but not 12-week, assessment. At 5 weeks post-taper, 79% of sodium valproate and 67% of trazodone, but only 31% of placebo patients were BZ-free (chi2 = 7.34; df 2; P<0.03). Major adverse events for trazodone were sedation and dry mouth, and for valproate, diarrhea, nausea and headaches.
Benzodiazepines have been used to treat a wide variety of disorders, including generalized anxiety disorder, panic disorder, sleep disorders, somatopsychic disorders, and depression. Concerns regarding physiologic dependence, withdrawal, and abuse potential with benzodiazepines prompted the development of strict guidelines for the use of these agents. Studies have shown that the risk of physiologic dependence increases with factors such as the dose of the benzodiazepine used and the duration of treatment. Restrictions involving benzodiazepines have led to the substitution of alternative medicines that may have decreased efficacy and greater safety concerns. There is a need for a more balanced assessment of the benefits and risks associated with benzodiazepine use to ensure that patients who would truly benefit from these agents are not denied appropriate treatment.
Many patients with depression take benzodiazepine drugs long term despite the absence of continuing therapeutic value.
To evaluate a treatment programme involving gradual discontinuation with or without simultaneous selective serotonin reuptake inhibitor (SSRI) prescribing and to determine the long-term outcome after benzodiazepine withdrawal.
Patients went through three phases - change to an equivalent dose of diazepam; subsequent randomisation to either 20 mg of paroxetine or placebo; and gradual reduction of diazepam in depression-free patients - with a follow-up after 2 or 3 years.
A total of 230 patients were recruited and 75% in the paroxetine group and 61% in the placebo group were successfully treated after 6 weeks (P:=0.067). After 2 or 3 years 13% of patients were still benzodiazepine free: 26% of those who had successfully tapered off benzodiazepine and 6% of the total group.
Transfer to diazepam followed by gradual withdrawal is an effective way of discontinuing chronic benzodiazepine use. The addition of SSRI treatment is of limited value.
The Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ, Tyrer et al. 1990) has been developed to measure distinct features of the benzodiazepine withdrawal syndrome. However, psychometric evaluations of this questionnaire are scarce. AIMS, SETTING: To evaluate the BWSQ during a discontinuation program carried out by general practitioners in 230 depressed chronic benzodiazepine users.
Reliability coefficients during the program were between 0.84 and 0.88 and the test-retest correlations were between 0.75 and 0.88 during withdrawal. Mean scores of the BWSQ during withdrawal differentiated between completers and failures (p = 0.036). The factor structure underlying the items consisted of perceptual and sensory disturbances, dysphoric mood, muscular pain and memory loss. Low scores during the last phase of tapering off predicted no, or limited, use of benzodiazepines in the first years following discontinuation (p = 0.003).
We found the BWSQ to measure symptoms during benzodiazepine withdrawal in a reliable way. Our findings indicate some construct validity for BWSQ. Low scores during withdrawal predict more limited future use of benzodiazepines.
To assess longitudinally the prescription of psychotropic drugs in depressed patients after they participated in a benzodiazepine discontinuation programme.
Two hundred and thirty depressed patients on chronic benzodiazepine therapy took part in a discontinuation programme conducted in 36 general practices. After 2.3 years (S.D.=0.65, range 0.1-3.6) medical records were reviewed.
Follow-up was achieved for 207 (90%) patients. Twenty-five (12%) patients remained benzodiazepine free during the full follow-up period. The majority (n=181, 87%) was prescribed benzodiazepines at an average of 13 (+/-14) mg of diazepam equivalents for 537 (+/-375) days. Fifty-five (74% of 74) of the successfully discontinued patients restarted benzodiazepine therapy. Sixty-eight (33%) patients were prescribed benzodiazepines during the whole follow-up period. Successful taper predicted no or lower subsequent benzodiazepine prescription rates (OR=7.3; 95% CI: 2-16). No influence of GP policy towards benzodiazepine prescription could be detected (P=0.275). Antidepressants were prescribed in 115 (55%) patients for an average duration of 476 (+/-360) days. There was no difference in benzodiazepine prescription (dosage, duration) between patients who had or had not been prescribed an antidepressant.
Patients were not been diagnosed systematically during the follow-up period.
If measured longitudinally, the rate of benzodiazepine prescription after discontinuation is much higher than reported in previous studies that have measured this cross-sectionally. Successful discontinuation is a strong predictor of modest or no future benzodiazepine prescription. Two-thirds of patients altered their benzodiazepine usage after taking part in a discontinuation programme. Treatment with antidepressants does not seem to influence benzodiazepine prescription. Patients' request (not GPs'policy) seems to be an important factor in continuing or resuming benzodiazepine prescription.
Comorbid conditions may add to the burden of depressed patients and hamper their treatment. We therefore investigated the impact of anxiety disorders and somatic comorbidity in a group of depressed chronic benzodiazepine users on disease status, treatment, benzodiazepine history and discontinuation outcome.
At screening for a discontinuation programme, full psychiatric status was determined using the MINI-interview and psychopathology was assessed using several rating scales. Relevant medical history, including surgeries, was recorded as well.
Patients with comorbid anxiety disorders were 8 years younger (p < 0.001), more anxious (p = 0.004) and reported more benzodiazepine withdrawal symptoms (p = 0.011) than depressed patients without comorbid anxiety disorders. They also had been using more long-acting benzodiazepines (p = 0.003), in higher dosages (p = 0.019). However, this did not result in more difficulty in tapering off benzodiazepines, either at post-test, or at follow-up 2.3 years later. Somatic comorbidity was not associated with the level of psychopathology and not related to the outcome of the discontinuation programme.
Comorbid anxiety disorders are associated with a more severe disease status in depressed chronic benzodiazepine users, but have no influence on the benzodiazepine discontinuation. Somatic comorbidity has no impact on the severity of the psychopathology, or on benzodiazepine discontinuation.
Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition.
To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice, and to evaluate the value of additional group cognitive-behavioural therapy (CBT).
A 3-month randomised, 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT, tapering off alone or usual care.
Tapering off led to a significantly higher proportion of successful discontinuations than usual care (62% nu. 21%). Adding group CBT did not increase the success rate (58% v. 62%). Neither successful discontinuation nor intervention type affected psychological functioning. Both tapering strategies showed good feasibilityin general practice.
Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice. The addition of group CBT is of limited value.
To assess the scalability, reliability and validity of a newly constructed self-report questionnaire on craving for benzodiazepines (BZs), the Benzodiazepine Craving Questionnaire (BCQ).
The BCQ was administered once to a sample of 113 long-term and 80 former long-term general practice BZ users participating in a large BZ reduction trial in general practice.
(1) Unidimensionality of the BCQ was tested by means of the Rasch model. (2) The Rasch-homogeneous BCQ items were assessed for subject and item discriminability. (3) Discriminative and construct validity were assessed.
The BCQ met the requirements for Rasch homogeneity, i.e. BZ craving as assessed by the scale can be regarded as a unidimensional construct. Subject and item discriminability were good. Construct validity was modest. Highest significant associations were found with POMS depression (Kendall's tau-c = 0.15) and Dutch Shortened MMPI negativism (Kendall's tau-c = 0.14). Discriminative validity was satisfactory. Highest discriminative power was found for a subset of eight items (Mann-Whitney U Z = - 3.6, P = 0.000). The first signs of craving are represented by the acknowledgement of expectations of positive outcome, whereas high craving is characterized by direct intention to use.
The BCQ proved to be a reliable and psychometrically sound self-report instrument to assess BZ craving in a general practice sample of long-term BZ users.
Low and medium potency benzodiazepines were initially introduced for the treatment of insomnia and anxiety. Their therapeutic actions as anxiolytics, sedative hypnotics, anticonvulsants, and muscle relaxants (with their low toxicity) have led to their use as first-line treatments, and they have become one of the most prescribed classes of drugs. Novel therapeutic uses of benzodiazepines were discovered with the introduction of the high-potency benzodiazepines (e.g., alprazolam, clonazepam, and lorazepam). They were found to be effective in treating panic disorder and panic attacks with or without agoraphobia, as add-on therapy to selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder and panic disorders, and as adjunctive therapy in treating patients with acute mania or acute agitation. High-potency benzodiazepines have replaced low and medium potency benzodiazepines in all benzodiazepine clinical indications due to their greater therapeutic effects and rapid onset of action. Differences in distribution, elimination half-life, and rate of absorption are important considerations when choosing a high-potency benzodiazepine. Typically, a benzodiazepine with long distribution and elimination half-lives is preferred. A maximum dose of 2 mg/day of any of the high-potency benzodiazepines when given for more than 1 week is recommended. Although as a class benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome.
Discontinuation of benzodiazepine (BZD) treatment for insomnia can be a difficult task. Cognitive-behavior therapy (CBT) for insomnia, combined with a supervised medication taper, can facilitate withdrawal but there is limited evidence on long-term outcome after discontinuation. The objective of this study was to examine medication-free survival time and predictors of relapse (i.e., resumed BZD hypnotics) over a 2-year period in 47 older adults (mean age 62.1 years) with persistent insomnia and prolonged BZD use (average duration of 18.9 years), who had successfully discontinued BZD following CBT for insomnia, a supervised medication taper program, or a combined approach. The Kaplan-Meier product-limit method was used to estimate survival time, defined as time between end-of-treatment and relapse or end of follow-up. By the end of the 24-month follow-up, 42.6% of the samples had resumed BZD use. Participants in the Combined (33.3%) and Taper (30.8%) groups relapsed significantly less than their counterparts from the CBT group (69.2%). Survival rates at 3 months were 61.5% (CBT), 100% (Taper), and 80.9% (Combined). At 12 months, they were 38.5%, 83.3%, and 70.8%, respectively; and, at 24 months, they were 28.9%, 64.8% and 64.9%, respectively. Mean survival time was significantly longer for both the Taper (18.6 months, SE = 2.1) and Combined groups (12.6 months, SE = 1.4), relative to the CBT group (8.5 months, SE = 1.8). Significant predictors of relapse included treatment condition, end of treatment insomnia severity, and psychological distress. In conclusion, there is a substantial relapse rate following BZD discontinuation among prolonged users. CBT booster sessions might enhance compliance with CBT and prove useful in preventing relapse.
This study aimed to assess benzodiazepine craving longitudinally and to describe its time course by means of the Benzodiazepine Craving Questionnaire (BCQ). Subjects were long-term benzodiazepine users participating in a two-part treatment intervention aimed to reduce long-term benzodiazepine use in general practice in The Netherlands. Four repeated measurements of benzodiazepine craving were taken over a 21-month follow-up period. Results indicated that (1) benzodiazepine craving severity decreased over time, (2) patients still using benzodiazepines experienced significantly more severe craving than patients who had quit their use after one of the two interventions, and (3) the way in which patients had attempted to quit did not influence the experienced craving severity over time, however, (4) patients who had received additional tapering off, on average, reported significantly more severe craving than patients who had only received a letter as an incentive to quit. Although benzodiazepine craving is prevalent among (former) long-term benzodiazepine users during and after discontinuation, craving severity decreases over time to negligible proportions. Self-reported craving can be longitudinally monitored and quantified by means of the BCQ.
Chronic benzodiazepine (BDZ) users often have difficulty with BDZ withdrawal. To examine clinical effects of selective serotonin reuptake inhibitor (SSRI) on tapering BDZ use in non-depressive patients, 97 outpatients with a history of BDZ use for at least 3 months were recruited at an internal medicine clinic of a university hospital. After the 4th edition of the Diagnostic and Statistical Manual (DSM-IV) clinical interviews for screening major depression, 66 outpatients (68%) without the DSM-IV major depression were randomly assigned to one of three groups: SSRI-assisted BDZ-reduction group (10-20 mg of paroxetine, n = 22), simple BDZ-reduction group (no paroxetine, n = 23), and reference group (no BDZ-reduction, n = 21). A standardized 8-week program involving gradual BDZ discontinuation was performed in the two BDZ-reduction groups. The Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the BDZ Withdrawal Symptom Questionnaire were assessed during the intervention period. Those with major depression were excluded from the BDZ-reduction intervention and treated with a different protocol of medication. In total, 10 (45.5%) in the SSRI-assisted BDZ-reduction group (n = 22) succeeded in becoming BDZ-free after completing the program, whereas only four (17.4%) in the simple BDZ-reduction group (n = 23) succeeded. The assistance of the SSRI significantly predicted the success of becoming BDZ-free (P = 0.023), controlling for the effects of age, gender, period of BDZ use, and baseline HAM-D and HAM-A scores. The score changes on the three questionnaires were comparable (all P > 0.05) among the three groups during the intervention period. The use of SSRI may have beneficial effects on BDZ withdrawal without the worsening of mood states in cases without major depression.
The objective of the study is to understand patient factors contributing to the chronicity of benzodiazepine use by older adults as a first step in the development of acceptable intervention strategies for taper/discontinuation or prevention of chronic use.
The design of the study consists of qualitative semi-structured patient interviews.
The participants were 50 anxiolytic benzodiazepine users, 61-95 years of age, recruited through referrals from primary care physicians who practiced in the general Philadelphia, Pennsylvania area.
Many older chronic users have come to rely and psychologically depend on benzodiazepines for their unique soothing properties, attributing to these medications characteristics that extend beyond an ordinary medication, i.e., affording control over daily stress, bringing tranquility, and even prolonging life. Most of the patients denied or minimized side effects and expressed resistance to taper or discontinuation, ranging from subtle reluctance to outright refusal and fear of being left suffering without these medications.
The reluctance of older chronic benzodiazepine users to taper or discontinue use highlights the importance of prevention and early intervention strategies to avoid the development of chronic use. Suggestions for curbing chronic use are presented.