Regular Benzodiazepine Research Articles

Benzodiazepine use in medical cannabis authorization adult patients from 2013 to 2021: Alberta, Canada

BackgroundBenzodiazepines are a class of medications that are being frequently prescribed in Canada but carry significant risk of harm. There has been increasing clinical interest on the potential “sparing effects” of medical cannabis as one strategy to reduce benzodiazepine use. The objective of this study as to examine the association of medical cannabis authorization with benzodiazepine usage between 2013 and 2021 in Alberta, Canada.MethodsA propensity score matched cohort study with patients on regular benzodiazepine treatment authorized to use medical cannabis compared to controls who do not have authorization for medical cannabis. A total of 9690 medically authorized cannabis patients were matched to controls. To assess the effect of medical cannabis use on daily average diazepam equivalence (DDE), interrupted time series (ITS) analysis was used to assess the change in the trend of DDE in the 12 months before and 12 months after the authorization of medical cannabis.ResultsOver the follow-up period after medical cannabis authorization, there was no overall change in the DDE use in authorized medical cannabis patients compared to matched controls (− 0.08 DDE, 95% CI: − 0.41 to 0.24). Likewise, the sensitivity analysis showed that, among patients consuming ≤5 mg baseline DDE, there was no change immediately after medical cannabis authorization compared to controls (level change, − 0.04 DDE, 95% CI: − 0.12 to 0.03) per patient as well as in the month-to-month trend change (0.002 DDE, 95% CI: − 0.009 to 0.12) per patient was noted.ConclusionsThis short-term study found that medical cannabis authorization had minimal effects on benzodiazepine use. Our findings may contribute ongoing evidence for clinicians regarding the potential impact of medical cannabis to reduce benzodiazepine use.Highlights• Medical cannabis authorization had little to no effect on benzodiazepine usage among patients prescribed regular benzodiazepine treatment in Alberta, Canada.• Further clinical research is needed to investigate the potential impact of medical cannabis as an alternative to benzodiazepine medication.

An audit of the pharmacological management of patients experiencing acute alcohol withdrawal at a large tertiary centre

Abstract Introduction Alcohol has depressant effects on the central nervous system through its effect on inhibitory GABAA receptors. In chronic excessive alcohol use, GABAA receptors undergo neuroadaptation, and so, in abrupt alcohol withdrawal upon admission into hospital, the central nervous system remains in a hyperactive state, resulting in alcohol withdrawal syndrome (AWS), and can progress to seizures and delirium tremens if not managed appropriately. National guidance recommends validated tools such as the ‘Clinical Institute Withdrawal Assessment – Alcohol, revised’ (CIWA-Ar) scale and use of benzodiazepines and thiamine for AWS management. Within our organisation, pharmacists and the Alcohol and Drug Liaison Nurse (ADLN) specialists have noted variability in AWS management. Aim This project aimed to investigate the compliance to local and national guidelines in the management of AWS. Methods A retrospective audit (for which ethical approval was not required) was conducted using the electronic health record system to identify high-risk drinkers on the acute medical unit (AMU). A report of AMU admissions from 1st to 30th April 2020 was obtained and identified 44 patients with AWS. Patient records were analysed to assess compliance to the following standards: Standard 1 was that 100% of patients must have a completed AUDIT-C form on admission; Standard 2 was that 100% with AWS must have a CIWA-Ar score recorded every 4 hours on day one; Standard 3 was that 100% must be prescribed a benzodiazepine reducing regimen as per guidelines; and Standard 4 was that 100% with malnourishment or who will continue to consume alcohol must be discharged with thiamine 200-300mg daily. Results For Standard 1, 2% of patients (n=1) had AUDIT-C forms completed. For Standard 2, 14% (n=6) had a CIWA-Ar score measured every 4 hours on day one. For Standard 3, 23% (n=10) were prescribed benzodiazepine fixed-dose reducing regimens according to their CIWA-Ar score. 23% (n=10) had no benzodiazepines prescribed and 30% (n=13) were only prescribed a ‘when required’ benzodiazepine. 48% (n=21) were prescribed a regular benzodiazepine initially rather than a reducing regimen. Of these, 62% (13/21) were commenced on an appropriate dose according to their CIWA-Ar score. For Standard 4, 34% (n=15) were discharged on oral thiamine 200-300mg daily. 27% (n=12) were discharged without thiamine. Discussion/Conclusion The use of AUDIT-C forms was not routine practice. This may lead to under-detection of patients experiencing AWS resulting in treatment delays. CIWA-Ar scores were rarely carried out every 4 hours on day one, perhaps highlighting a need for guidance on frequency of CIWA-Ar assessment. Ten patients with AWS were not prescribed a benzodiazepine. This could have been due to a lack of awareness of guidelines, or that simplification of current guidelines is required. Limitations of this audit include that it did not explore clinical reasons for deviations from guidelines or any additional specialist advice sought from ADLN. As such, it cannot be assumed that all deviations from guidelines were inappropriate. No audit standards were met, highlighting a need to improve management of AWS in a hospital setting.

Quality Use of Medicines Indicators and Associated Factors in Residential Aged Care Facilities: Baseline Findings from the Pharmacists in RACF Study in Australia.

Prescribing potentially inappropriate medications (PIMs), including antipsychotics and benzodiazepines, has been used as an indicator of the quality use of medicines in residential aged care facilities (RACFs). PIMs are associated with an increased risk of falls and hospitalisations in the elderly. The purpose of this study is to assess the extent of prescribing of PIMs in RACFs at baseline in the Pharmacists in residential aged care facilities (PiRACF) study and examine the association of resident and system factors with the number of PIMs. A cross-sectional analysis of 1368 participants from 15 Australian RACFs was performed to detect PIMs using the American Geriatrics Society 2019 Beers® criteria. Most residents (68.1%) were taking at least one regular PIM; 16.9% were taking regular antipsychotics and 11.1% were taking regular benzodiazepines. Long-term proton pump inhibitors were the most frequent class of PIMs. History of falls and higher Charlson Comorbidity Index were associated with an increased number of prescribed PIMs, while dementia diagnosis and older age (85 years or more) were associated with decreased number of PIMs (p-value <0.05). Residents in facilities with lower nurse-to-resident ratios were more likely to have an increased number of PIMs (p value = 0.001). This study indicates that potentially inappropriate prescribing is common in RACFs and interventions to target residents at highest risk are needed.

Long-term anticholinergic, benzodiazepine and Z-drug use in community-dwelling older adults: What is the impact on cognitive and neuropsychological performance?

Long-term use of anticholinergics, benzodiazepines and related drugs (or "Z-drugs") have been associated with cognitive impairment and dementia. However, the relationship of these medications with cognitive function and domain-specific neuropsychological performance in older adults without dementia, is unclear. 5135 older adults (74.0±8.3 years; 67.4% female) without a diagnosis of dementia were recruited in Ireland to the Trinity-Ulster-Department of Agriculture (TUDA) study. Detailed cognitive and neuropsychological assessment was conducted using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). A total of 44% (2259 of 5153) used either a potential or definite anticholinergic medication. Overall, 9.7% (n=500) used a definite anticholinergic medication. Regular benzodiazepine use was reported by 7% (n=363), whilst 7.5% (n=387) used a "Z-drug". Use of definite, but not potential anticholinergic medication was associated with poorer performance on all three assessments (β: -0.09; 95% CI: -0.14, -0.03, p=0.002 for MMSE; β: -0.04; 95% CI: -0.06, -0.02; p<0.001 for FAB; β: -4.15; 95% CI: -5.64, -2.66; p<0.001 for RBANS) in addition to all domains of the RBANS. Regular benzodiazepine use was also associated with poorer neuropsychological test performance, especially in Immediate Memory (β: -4.98; 95% CI: -6.81, -3.15; p<0.001) and Attention (β: -6.81; 95% CI: -8.60, -5.03; p<0.001) RBANS domains. Regular use of definite anticholinergic medications and benzodiazepines, but not potential anticholinergics or "Z-drugs", was associated with poorer overall and domain-specific neuropsychological performance in older adults.

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

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

Preliminary investigation into the identification and management of catatonia in patients admitted to adult inpatient units

AimsThe prevalence of catatonia is considered to be approximately 10% in psychiatric inpatients. Clinical experience suggests a lower documented prevalence. This could cause longer admissions and complications, such as Neuroleptic Malignant Syndrome (NMS). We carried out a service evaluation to investigate the recognition and management of catatonia on inpatient units in Southern Health Foundation Trust (SHFT). We reviewed the local documented prevalence of catatonia, treatment offered and prevalence of complications.MethodWe retrospectively reviewed the electronic records of 95 consecutive admissions to four adult inpatient units in SHFT, starting on 1st August 2020. We reviewed notes for the admission to establish whether catatonia was suspected and identified. We applied the screening questions from the Bush-Francis Catatonia Rating Scale (BFCRS) to the documented mental state examinations (MSE) prior to, and shortly after, admission. We also recorded the prescriptions issued during the first 72 hours of admission, and whether patients developed neuroleptic malignant syndrome (NMS), serotonin syndrome or required admission to a general hospital during admission.ResultCatatonia was documented as a possibility for 2 patients (2.1%). One showed possible posturing and stupor, while there were no documented symptoms for the other. In both cases the possibility was discounted by the clinical team. Twelve patients (12.6%) showed one or more possible or confirmed signs of catatonia. Eleven of these were prescribed regular antipsychotic medication on admission, but only 3 were prescribed regular benzodiazepines. NMS was more likely to be suspected in patients with a BFCRS of 1 or more compared with those with a score of 0, with an odds ratio of 8.1 (95% CI [1.03-64.0], Fisher's exact test = 7.79, p = .076).ConclusionCatatonia is likely under-recognised and under-treated locally among psychiatric inpatients. Although only approaching statistical significance, the higher rate of suspected NMS in patients showing possible catatonia is noteworthy and needs further investigation. Regular benzodiazepines were not frequently prescribed in this group, while antipsychotics, prescribed in all of these patients, can precipitate NMS. Alternatively, this finding could reflect the overlap in clinical presentation between NMS and catatonia. Data collection was limited by the frequent use of “remote clerking”, in the context of the COVID-19 pandemic. Additionally, the quality of mental state examinations was often not sufficient to draw any conclusions on the possible presence or absence of catatonic symptoms. This project has highlighted practice in need of improvement, which will be further prospectively investigated and improved via a Quality Improvement Project.

The use of antipsychotic polypharmacy at Ravenswood House Medium Secure Unit: the extent of use and reporting of outcomes

AimsTo evaluate the use of antipsychotic polypharmacy in Ravenswood House Medium Secure Hospital. We also aimed to review the reporting of the outcomes of their use.BackgroundThe use of antipsychotic polypharmacy (APP) continues to be practised within forensic psychiatric inpatient settings yet there is a lack of robust evidence for the benefits of doing so. The practice is also associated with the use of higher total antipsychotic doses beyond the recommended BNF maximum. Such prescribing is associated with an increased side effect burden. Doctors have a duty to justify the ongoing use of antipsychotic polypharmacy and to avoid potentially ineffective and/or harmful use.MethodA cross-sectional review of the medication cards for 51 in-patients at Ravenswood House Hospital was completed. Demographic data and data pertaining to diagnoses and medication was also gathered from the electronic patient records.Result23 patients (45%) in Ravenswood House Hospital were prescribed antipsychotic polypharmacy. 87% of those prescribed antipsychotic polypharmacy had a primary diagnosis of either schizophrenia or schizoaffective disorder. 19 patients (37%) had two regular antipsychotics prescribed. 74% of these prescriptions were above the recommended BNF maximum. 62% were also prescribed a regular benzodiazepine. The vast majority of indications documented for APP were chronic behavioural disturbance and treatment resistant schizophrenia. The majority of these patients were on a T3. There was a significant under reporting of the rationale of prescribing APP. It could be surmised that at least 11 combinations were in part to mitigate side effects, but only 3 had this documented. There was also a lack of documentation or use of rating scales regarding the clinical outcomes and side effects of APP.ConclusionPrescription of antipsychotic polypharmacy is an important issue in secure forensic hospital settings. The lack of clear documentation of clinical effectiveness and side effect burden remains a concern. Wider study is required to establish the benefits of such prescribing to justify its ongoing use.

Management of Agitation in Dementia and Effects on Inpatient Length of Stay.

BackgroundAgitation associated with dementia impacts delivery of medical care and is a major reason for institutionalization in dementia patients. This study examines the association of medication use and other clinical factors with patients’ ‘dischargeability’ (i.e., amount of time until a patient is considered dischargeable from an inpatient unit).MethodsThis study was a retrospective chart review examining 200 patients with dementia and agitation, hospitalized at a Canadian acute care geriatric ward between November 2007 and November 2018. The main outcome measure was time until a patient was deemed dischargeable. Univariate linear regression analyses, followed by multiple linear regression analyses, were used.ResultsRisperidone and quetiapine were the most commonly prescribed medications, but were not associated with time until dischargeable. Olanzapine (40.9 vs. 16.2 days until dischargeable, β = 0.23, p = .001), regular benzodiazepine (32.7 vs. 16.5 days until dischargeable, β = 0.15, p = .027), and as-needed (‘PRN’) benzodiazepine use (31.7 vs. 15.9 days until dischargeable, β =0.19, p = .006) were independently associated with prolonging time until dischargeable.ConclusionsOlanzapine, benzodiazepine, and PRN benzodiazepine use were associated with longer time until patients with dementia and agitation were considered ready for discharge. This raises the question as to whether the risks of these medications outweigh the benefits in a hospital setting.

EFFECTS OF BENZODIAZEPINES ON ORTHOSTATIC BLOOD PRESSURE IN OLDER PEOPLE

Objective: Older people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to unfavorable drug-related effects on cognition and psychomotor functioning. BDZs may also have hypotensive effects, but evidence concerning their consequences on orthostatic blood pressure (BP) behaviour is scarce. We investigated the association between BDZs and BP response to an active stand test in older people. Design and method: We performed a retrospective analysis of data from an outpatient research clinic in an Irish university hospital, where people aged 60 or older underwent a comprehensive geriatric assessment between August 2007 and May 2009. Non-invasive beat-to-beat orthostatic BP was measured during an active stand, with systolic BP assessed at each 10-second interval. Information on regular BDZs use was collected. Factors independently associated with orthostatic systolic BP were investigated using multiple linear regression. Results: Of 538 participants (67.7% female, mean age 72.7 ± 7.2), 33 (6.1%) reported regular use of BDZs. During active stand, participants taking BDZs showed a significantly greater systolic BP drop 10 seconds after the posture change (“immediate” BP drop), while no significant differences were detected in orthostatic systolic BP in the latter phases of standing. After adjusting for possible confounders, BDZs use was independently associated with a mean immediate systolic BP drop of 12 mmHg after standing. Conclusions: Older people taking BDZs may have higher risk of an immediate systolic BP drop after standing, adding to other BZD-related falls risks. BDZs should be avoided in older people at risk of falling.

Characterization of self-anticipated pain score prior to elective surgery - a prospective observational study

BackgroundCurrent principles of postoperative pain management are primarily based on the types and extent of surgical intervention. This clinical study measured patient’s self-anticipated pain score before surgery, and compared the anticipated scores with the actual pain levels and analgesic requirements after surgery.MethodsThis prospective observational study recruited consecutive patients who received elective surgery in the E-Da Hospital, Taiwan from June to August 2018. Patients were asked to subjectively rate their highest anticipated pain level (numeric rating scale, NRS 0–10) for the scheduled surgical interventions during their preoperative anesthesia assessment. After the operation, the actual pain intensity (NRS 0–10) experienced by the patient in the post-anesthesia care unit and the total dose of opioids administered during the perioperative period were recorded. Pain scores ≥4 on NRS were regarded as being unacceptable levels for anticipated or postoperative pain that required more aggressive intervention.ResultsA total of 996 patients were included in the study. Most of the patients (86%) received general anesthesia and 73.9% of them had a history of previous operation. Female anticipated significantly higher overall pain intensities than the male patients (adjusted odd ratio 1.523, 95% confidence interval 1.126–2.061; P = 0.006). Patients who took regular benzodiazepine at bedtime (P = 0.037) and those scheduled to receive more invasive surgical procedures were most likely to anticipate for higher pain intensity at the preoperative period (P < 0.05). Higher anticipated pain scores (preoperative NRS ≥ 4) were associated with higher actual postoperative pain levels (P = 0.007) in the PACU and higher total equivalent opioid use (P < 0.001) for acute pain management during the perioperative period.ConclusionThis observational study found that patients who are female, use regular benzodiazepines at bedtime and scheduled for more invasive surgeries anticipate significantly higher surgery-related pain. Therefore, appropriate preoperative counseling for analgesic control and the management of exaggerated pain expectation in these patients is necessary to improve the quality of anesthesia delivered and patient’s satisfaction.

428 - DEMENTIA INPATIENT THERAPEUTIC INTERVENTIONS IN A SCOTTISH HEALTH REGION

Background: There is published evidence of the benefits and limitations, including potential harm, of psychotropic medication and benefits of non-pharmacological interventions for the management of challenging behaviours associated with dementia (BPSD).Objectives: To examine the usage of such interventions in the management of BPSD within three National Health Service (NHS) ‘specialist’ dementia inpatient wards (56 beds) in a Scottish health region (Fife, population 370,000) and to identify targets for service improvements.Methods: Patient demographic data, mental and physical health diagnoses, current and recent (within 3 months) psychotropic prescriptions, multidisciplinary team input, and evidence of individualised non-pharmacological interventions for BPSD were collected in February 2020 from patient notes, care plans and medication charts.Results: 42 older patients (mean age 80 years, range 59-99) with dementia had spent on average 18.7 months within hospital, some categorised as ‘delayed discharges’ awaiting care home placements All lacked capacity to consent to their general care and medical treatments, most having multiple (average 5) medical co-morbidities. 36% were detained in hospital under Mental Health legislation, 29% prescribed medications so authorised, and 40% had medications administered covertly. 76% were prescribed an antipsychotic (Risperidone in 24%), 40% a cognitive enhancer (Memantine and/or a cholinesterase inhibitor), 48% an antidepressant (Trazodone in 19%), 26% a regular benzodiazepine. There was limited regular multi-professional team working in the wards (under 18% had any non-nursing input within the previous 3 months). Of non-pharmacological therapeutic interventions, 26% were receiving multisensory inputs, 19% soft toy, 12% massage, 7% music playlist and 7% cognitive stimulation therapy.Conclusions: For this population with BPSD there were high rates of off -licence drug prescribing with limited investment in evidence-based non-pharmacological therapeutic alternatives. During ongoing review of staffing on these wards, it would appear appropriate to examine the expectation that wards serve multiple functions, such as transitional care and specialist continuing care. We suggest reviews contextualise prescribing within an increased availability of multi-disciplinary therapeutic interventions, to ensure this patient population is cared for in an evidence-based therapeutic environment. The Scottish Government’s publication3 (2018) “Transforming Specialist Dementia Hospital Care” should help raise the profile of this “overlooked” inpatient population.3https://www.gov.scot/publications/transforming-specialist-dementia-hospital-care/

13 Effects of Benzodiazepines on Orthostatic Blood Pressure in Older People

Abstract Background Older people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to unfavorable drug-related effects on cognition and psychomotor functioning. BDZs may also have hypotensive effects, but evidence concerning the relationship between BDZs and orthostatic blood pressure (BP) behaviour in older people is scarce. We investigated the effects of BDZs on BP response to an orthostatic active stand test. Methods We performed a retrospective analysis of data from an outpatient research clinic in an Irish university hospital, where people aged 60 or older underwent a comprehensive geriatric assessment between August 2007 and May 2009. Non-invasive beat-to-beat orthostatic BP was measured during active stand, with systolic BP assessed at each 10-second interval. Information on regular BDZs use was collected. Factors independently associated with orthostatic systolic BP were investigated using multiple linear regression. Results Of 624 community-dwelling people who underwent a clinic assessment, orthostatic active stand data was collected in 541. Information on regular BDZs use was available in 538 people. Of 538 participants, mean age was 72.7±7.2, 67.7% were female and 33 (6.1%) reported regular use of BDZs. History of falls (p=0.027) and fear of falling (p&lt;0.001) were more prevalent in this subgroup. During active stand, participants on BDZs showed a significantly greater systolic BP drop 10 seconds after the posture change (“immediate” BP drop). No significant differences were detected in orthostatic systolic BP in the latter phases of the active stand. After adjusting for possible confounders, BDZs use was independently associated with a mean immediate systolic BP drop of 12 mmHg after standing. Conclusion BDZs may confer higher risk of an immediate systolic BP drop after standing in older people, which may contribute to their known falls risk. BDZ should be avoided in older people at risk of falling.

Prevalence and correlates of benzodiazepine use and misuse among young adults who use prescription opioids non-medically

BackgroundBenzodiazepine use dramatically increases the risk of unintentional overdose among people who use opioids non-medically. However, little is known about the patterns of co-occurring benzodiazepine and opioid use among young adults in the United States. MethodsThe Rhode Island Young Adult Prescription Drug Study (RAPiDS) was a cross-sectional study from January 2015—February 2016. RAPiDS recruited 200 young adults aged 18–29 who reported past 30-day non-medical prescription opioid (NMPO) use. Using Wilcoxon rank sum test and Fisher’s exact test, we examined correlates associated with regular prescribed and non-medical use (defined as at least monthly) of benzodiazepines among NMPO users in Rhode Island. ResultsAmong participants, 171 (85.5%) reported lifetime benzodiazepine use and 125 (62.5%) reported regular benzodiazepine use. Nearly all (n=121, 96.8%) reported non-medical use and 43 (34.4%) reported prescribed use. Compared to the 75 participants who did not regularly use benzodiazepines, participants who reported regular use were more likely to be white (66.3% vs. 58.0%, p=0.03), have ever been incarcerated (52.8% vs. 37.3%, p=0.04), and have ever been diagnosed with a psychiatric disorder (bipolar: 29.6% vs. 16.0%, p=0.04; anxiety: 56.8 vs. 36.0%, p=0.01). Although the association was marginally significant, accidental overdose was higher among those who were prescribed the benzodiazepine they used most frequently compared to those who were not (41.9% vs. 24.4%, p=0.06). ConclusionBenzodiazepine use and misuse are highly prevalent among young adult NMPO users. Harm reduction and prevention programs for this population are urgently needed.

PP.16.16] REGULAR BENZODIAZEPINES CONSUMPTION ASSOCIATED WITH LOWER BLOOD PRESSURE IN AMBULATORY BLOOD PRESSURE MONITORING

Objective: It has been previously demonstrated that benzodiazepines can help reduce acute elevation of blood pressure in hypertensive patients. However, the effect of regular benzodiazepine use on blood pressure has not been documented. In the current study, we aimed to evaluate whether benzodiazepine use (for at least 3 months) can be associated to the results of ambulatory blood pressure monitoring (ABPM). Design and method: A retrospective analysis of the ABPM database between 2009 and 2015 was performed. The study groups were divided according to benzodiazepine treatment at least 3 months before an ABPM. Multivariate analysis using Generalized estimating equation (GEE) linear model was conducted to estimate the association between benzodiazepine treatment and ABPM test measurements: 24 h, daytime, and nighttime systolic and diastolic blood pressure. Results: A total of 5020 ABPM studies were included in final analysis, including 713 ABPM of benzodiazepine-treated patients, and 4307 of untreated patients. The benzodiazepine-treated group was significantly older, with a predominance of female patients, comprised more diabetic patients and patients who consumed more antihypertensive medications. After adjustment for age, gender, diabetes mellitus, and number of antihypertensive medications taken, benzodiazepine treatment was independently associated with significantly lower systolic blood pressure over 24 h, during the daytime, and during the night [−2.176 mmHg (−3.377;−0.974); −2.040 mmHg (−3.268;−0.812) and −2.11 mmHg (−3.486;−0.733) respectively] as well as with significantly lower diastolic blood pressure over 24 h, during the daytime and during the night [−1.802 mmHg (−2.558;−1.047); −1.720 mmHg (−2.502;−0. 939), and −1.788 mmHg (−2.610;−0.966) respectively]. Analysis stratified by age of 60 revealed that benzodiazepine consumption was associated with lower ABPM measurements only in the elderly group. Conclusions: Use of benzodiazepines was independently associated with lower diastolic and systolic blood pressure in all parameters of ABPM in patients 60 years old and older, while not among younger patients.

The association between benzodiazepine use and sleep quality in residential aged care facilities: a cross-sectional study.

BackgroundBenzodiazepines are commonly prescribed in residential aged care facilities (RACFs) for their sedative and anxiolytic effects. The objective of this study was to investigate the association between benzodiazepine use and sleep quality in residents of RACFs.MethodsA cross-sectional study involving 383 participants was conducted in six Australian RACFs. Night-time sleep quality, day-time drowsiness and day-time napping behavior were assessed using a validated questionnaire. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the association between benzodiazepine use and sleep quality. Covariates included pain, dementia severity, depression, insomnia and other sedative use.ResultsOf the 383 residents (mean age 87.5 years, 77.5% female), 96(25.1%) used a benzodiazepine on a regular basis. Residents who used long-acting benzodiazepines on a regular basis had higher night-time sleep quality than non-users (AOR = 4.00, 95%CI 1.06 – 15.15). Residents who used short-acting benzodiazepines on a PRN only basis had longer daytime napping times than non-users (AOR = 1.77, 95%CI 1.01 – 3.08). No benzodiazepine category was associated with day-time drowsiness.ConclusionsThe association between benzodiazepine use and sleep quality is dependent on the half-life and prescribing pattern of the benzodiazepine. Short-acting PRN benzodiazepines were associated with lower night time sleep quality and longer day-time napping compared to long-acting regular benzodiazepines. Longitudinal studies are needed to determine whether these findings reflect channeling of short-acting agents to residents at higher risk of sleep disorders.

Regular Benzodiazepine and Z-Substance Use and Risk of Dementia: An Analysis of German Claims Data.

While acute detrimental effects of benzodiazepine (BDZ), and BDZ and related z-substance (BDZR) use on cognition and memory are known, the association of BDZR use and risk of dementia in the elderly is controversially discussed. Previous studies on cohort or claims data mostly show an increased risk for dementia with the use of BDZs or BDZRs. For Germany, analyses on large population-based data sets are missing. To evaluate the association between regular BDZR use and incident any dementia in a large German claims data set. Using longitudinal German public health insurance data from 2004 to 2011 we analyzed the association between regular BDZR use (versus no BDZR use) and incident dementia in a case-control design. We examined patient samples aged≥60 years that were free of dementia at baseline. To address potential protopathic bias we introduced a lag time between BDZR prescription and dementia diagnosis. Odds ratios were calculated applying conditional logistic regression, adjusted for potential confounding factors such as comorbidities and polypharmacy. The regular use of BDZRs was associated with a significant increased risk of incident dementia for patients aged≥60 years (adjusted odds ratio [OR] 1.21, 95% confidence interval [CI] 1.13-1.29). The association was slightly stronger for long-acting substances than for short-acting ones. A trend for increased risk for dementia with higher exposure was observed. The restricted use of BDZRs may contribute to dementia prevention in the elderly.

How do we compare with best practice? A completed audit of benzodiazepine and z-hypnotic prescribing.

To compare benzodiazepine and z-hypnotic prescribing practices in an inpatient psychiatric unit to best practice standards. Medication charts of all inpatients in the psychiatric unit, over a 1-week period, were reviewed. Details of current benzodiazepine and z-hypnotic prescriptions were collected. Information collected included the substance prescribed, duration and administration instructions. Feedback was communicated to medical practitioners through a presentation and email. A re-audit was completed 4 months later. There were increases in total benzodiazepine and z-hypnotic prescribing despite intervention. A reduction of 2 mg occurred in the mean regular dose of benzodiazepine prescribed. Lorazepam was the most prescribed benzodiazepine throughout. In both data sets, at least 50% of regular z-hypnotics and benzodiazepines were initiated before admission. There was an increase of 14% in regular benzodiazepines initiated in hospital exceeding 4 weeks in duration. In neither data collection did regular z-hypnotics initiated in hospital exceed this cut off. A greater number of individuals were in the process of being withdrawn from regular benzodiazepine or z-hypnotic prescriptions in the re-audit. There were minimal improvements in 'as required' prescribing as regards documentation of an indication, time limit and maximum dose. The increase in overall prescribing, despite intervention, maybe because these medications continued to be indicated in the acute presentations needing inpatient treatment. The small improvements in 'as required' prescribing patterns suggest that the intervention was limited in effecting change in this area.

High-Dose Benzodiazepines May Increase Risk of Death in Schizophrenia Patients

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessHigh-Dose Benzodiazepines May Increase Risk of Death in Schizophrenia PatientsMark MoranMark MoranSearch for more papers by this authorPublished Online:4 Feb 2016https://doi.org/10.1176/appi.pn.2016.1b14AbstractUse of antipsychotics or antidepressants was associated with overall mortality rates 15 to 40 percent lower compared with no use of these medications.Chronic, high-dose use of benzodiazepines among patients with schizophrenia appears to be associated with a markedly higher overall mortality rate than is seen in patients with schizophrenia who have not been exposed to benzodiazepines, according to a report in AJP in Advance (December 7, 2015).The report also found a lower overall mortality rate among patients with schizophrenia who received antipsychotics and/or antidepressants.“The results indicate that any amount of antipsychotic and antidepressant usage is associated with overall mortality rates 15 percent to 40 percent lower compared with no use of these medications,” wrote study authors Jari Tiihonen, M.D., Ph.D., and colleagues at the Karolinska Institutet in Stockholm. “In contrast, benzodiazepine exposure revealed a clear dose-response curve for mortality, where high exposure was associated with a 70 percent higher risk of death compared with no use.”The authors prospectively compared all-cause and cause-specific mortality in individuals aged 16 to 65 who had been diagnosed with schizophrenia (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010. The cohort participants were identified from two nationwide Swedish health care registers.Compared with 214,670 age- and gender-matched persons from the general population, the mortality of the cohort with schizophrenia was 4.8-fold higher. The most common specific cause of death was cardiovascular disease (32.7 percent), followed by neoplasms (16.5 percent), respiratory diseases (11.0 percent), and suicide (9.5 percent). Any degree of exposure to antipsychotics or antidepressants was associated with a lower overall mortality compared with no use. The opposite was observed for benzodiazepines, and high exposure was associated with a 74 percent higher risk of death compared with no use. “The association between benzodiazepine exposure and mortality may be explained by several mechanisms,” the authors noted. “Although long-term benzodiazepine use may be a marker for more severe illness and coexisting substance abuse, it is also plausible to assume that prescribing of high doses for long periods may lead to tolerance and dose escalation. This could result in fatal interactions with concurrent use of alcohol and illicit drugs, and worsening of polysubstance dependence may result in a less healthy lifestyle in general. In addition, high-dose benzodiazepine use may also contribute to daytime sedation and proneness to accidents.”Although adverse events associated with antipsychotics have received considerable attention, the study authors emphasized that their findings suggest that patients on high doses of benzodiazepines should be monitored closely.“It is important to realize that although monitoring of patients with moderate- or high-dose antipsychotic treatment is relevant, it is essential to focus the preventive interventions on those patients who have an even higher risk of death, that is, patients not using antipsychotics and patients using high doses of benzodiazepines,” they wrote. AJP Editor Robert Freedman, M.D., cautioned that the study is not necessarily an indictment of benzodiazepines and noted that high-dose use among people with schizophrenia appears to be more common in Sweden than in the United States. “Dr. Tiihonen and colleagues fulfill the maxim that great epidemiologists raise more questions than they answer,” he told Psychiatric News. “As the authors of the study point out, regular benzodiazepine use in addition to antipsychotics likely indexes a more severely ill group of patients. “The message for clinicians is that use of benzodiazepines to avoid the toxicity of antipsychotics seems to have its own problematic consequences,” Freedman continued. “A second message is that Tiihonen and colleagues found that antidepressant use decreases mortality and should be considered as a beneficial therapeutic addition for schizophrenia.” This research was supported by Karolinska Institutet, Niuvanniemi Hospital in Kuopio, Finland, and the Sigrid Juselius Foundation. ■“Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study” can be accessed here. ISSUES NewArchived

Correlates of benzodiazepine use in major depressive disorder: The effect of anhedonia

BackgroundCurrent treatment guidelines emphasize the limited role of benzodiazepines in Major Depressive Disorder (MDD), mainly due to the absence of long-term data, risk of abuse and potential adverse effects. However, benzodiazepines continue to be prescribed for long-term use in a significant number of patients. This study sought to evaluate benzodiazepine use in a large sample of MDD patients seen at a tertiary care clinic, and determine whether use is related to illness severity or complexity, as well as to identify the clinical predictors of benzodiazepine use. MethodsThis was a naturalistic cross-sectional study conducted in MDD patients seen at the Mood Disorders Pyschopharmacology Unit at the University Health Network (N=326). Detailed information on current medication regimens was collected. A structured diagnostic interview, in addition to measures of symptom severity, quality of life, and personality were administered. Participants were grouped according to the presence or absence of prescribed benzodiazepines for daily use. ResultsThe prevalence of regular benzodiazepine use was 25%. Benzodiazepine users were more likely to be female, unemployed, have a history of child abuse, and have comorbid panic disorder. Depression and anxiety scores were not significantly different between groups, although anhedonia was greater in the benzodiazepine group. A logistic regression revealed anhedonia was the strongest predictor of regular benzodiazepine use. ConclusionThe groups were similar in clinical profile suggesting benzodiazepine use is not necessarily linked to greater illness complexity or severity. Benzodiazepine use appears to be associated with specific diagnostic and symptom characteristics, possibly providing insight into the potential pharmacodynamic and neurobiological effects of frequent use.

Benzodiazepine Use Among Young Attendees of an Irish Substance Treatment Center

To describe the demographic characteristics of those service users attending Matt Talbot Services, and their current and past substance use, and to explore the use of benzodiazepines among this group. There were 198 service users who attended a substance misuse treatment center in Cork, Ireland, between January 2005 and August 2011. Benzodiazepines had ever been used by 51.0%, and of these, 55.8% were regular benzodiazepine users. The mean age of first use was 14.9 ± 1.4 years. Regular users of benzodiazepines were regular users of significantly more substances (3, interquartile range [IQR] = 2-3) when compared with nonregular benzodiazepine users (1, IQR = 1-2). Regular benzodiazepine users showed more behavioral signs (12, IQR = 10-14) than nonregular users (9, IQR = 7-12). Physical signs were significantly different between regular (8, IQR = 6-11) and nonregular (5, IQR = 3-10) users. The effects of benzodiazepine misuse affect the individual, their family, and society as a whole through hospitalization, substance treatment, and crime. Identifying regular benzodiazepine users can help reduce the burden of benzodiazepines.