Impact of narcotics information management system on inappropriate benzodiazepine receptor agonist prescriptions: A quasi-experimental analysis in South Korea.

AIMS: The South Korean government implemented the narcotics information management system (NIMS) on 18 May 2018 to manage benzodiazepine receptor agonists (BzRAs) and narcotics effectively and establish a reporting mechanism for these drugs. This study assessed the effects of NIMS on inappropriate use of BzRAs. METHODS: Using national patient sample data from 2016 to 2020, we analysed adult outpatients who were prescribed oral BzRAs. We conducted a time series and segmented regression analysis using selected indicators to analyse the monthly variations related to the inappropriate use of these medications. RESULTS: The study revealed no significant changes in the indicators of inappropriate BzRA use following the NIMS implementation. Contrary to expectations, there was a significant increase in the proportion of patients exceeding defined daily dose (DDD) and in those receiving concurrent prescriptions of multiple BzRAs, following the implementation of NIMS. The immediate impact of the COVID-19 pandemic was an increase in DDD exceedance; however, overall, this did not significantly affect BzRA use. CONCLUSIONS: The introduction of NIMS did not significantly enhance the management of BzRA misuse. Additional measures, including continuous monitoring, system improvements and comprehensive education for prescribers and patients, are recommended to ensure the appropriate use of psychotropic medications.

Comparison of patients with benzodiazepine receptor agonist-related psychiatric disorders and over-the-counter drug-related psychiatric disorders before and after the COVID-19 pandemic: Changes in psychosocial characteristics and types of abused drugs.

AIM: To investigate changes in the clinical characteristics of patients who abused benzodiazepine receptor agonists (BZRA) or over-the-counter (OTC) drugs before and after COVID-19 based on the 2018 and 2022 data of the "Nationwide Psychiatric Hospital (NPH) Survey on Drug-related Psychiatric Disorders." METHOD: A total of 446 and 155 cases, and 435 and 273 cases, who mainly abused BZRAs or OTC drugs, respectively, were extracted from the database of the two NPH Surveys. Demographic variables, education, employment, criminal record, drug use during the previous year, psychiatric diagnosis, and types of abused drugs were compared between 2018 and 2022. RESULT: A comparison of BZRA abusers revealed a decreased number of users during the previous year and an increase in the comorbidity rate of other disorders (F3 and F4 in ICD-10) in 2022. Etizolam, flunitrazepam, triazolam, and zolpidem were used most in both years, with an increase in zolpidem and a decrease in triazolam in 2022. A comparison of OTC drug abusers revealed a higher proportion of women and young patients in 2022. An increase in the comorbidity rate of F3 and F9 and a significant increase in the use of dextromethorphan products were observed in 2022, although codeine products were in the majority in both years. CONCLUSION: By comparing NPH Surveys before and after the COVID-19 pandemic, both BZRA abusers and OTC drug abusers present complex pathologies, requiring tailor-made treatment. The younger OTC drug abusers were particularly evident among women, and the abuse of dextromethorphan-containing OTC drugs has increased alarmingly.

Pharmacokinetics and exposure-safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit.

Ciprofol (HSK3486) is a newly developed, highly selective γ-aminobutyric acid-A (GABAA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinical trials of healthy subjects were used in the PopPK analysis. Exposure-safety relationship for hypotension was evaluated based on the data gathered from 112 subjects in two clinical trials of mechanically ventilated patients in the ICU. Ciprofol pharmacokinetics (PKs) was adequately described by a three-compartment linear disposition model with first-order elimination. Body weight, age, sex, blood sampling site (vein vs. arterial), study design (long-term infusion vs. short-term infusion), and patient population (ICU vs. non-ICU) were identified as statistically significant covariates on the PKs of ciprofol. Within the exposure range of the mechanically ventilated ICU patient population, no meaningful association was observed between ciprofol exposure and the incidence of hypotension. These results support the dosing regimen currently used in mechanically ventilated patients in the ICU.

[Anxiolytics: Appropriate Use of Benzodiazepine Receptor Agonists].

Anxiolytics are a class of drugs that include benzodiazepine receptor agonists and serotonin 1A receptor partial agonists. Although benzodiazepine receptor agonists have anxiolytic, sedative-hypnotic, muscle relaxant, and anticonvulsant effects, their use should be carefully monitored due to their potential for paradoxical reactions, withdrawal symptoms, and dependence. On the other hand, serotonin 1A receptor partial agonists have a slower onset, and their use also presents challenges. In clinical practice, having a thorough understanding of the various types of anxiolytics and their unique features is crucial.

Effects of Bedtime Dosing With Suvorexant and Zolpidem on Balance and Psychomotor Performance in Healthy Elderly Participants During the Night and in the Morning.

PURPOSE/BACKGROUND: This study was designed as an early assessment of the safety of the orexin receptor antagonist suvorexant, but also included exploratory assessments of balance and psychomotor performance that are the focus of this report. METHODS/PROCEDURES: This was a double-blind, randomized, 3-period, crossover, phase 1 study. Balance and psychomotor performance were evaluated during the night in 12 healthy elderly participants after bedtime administration of suvorexant 30 mg (a supratherapeutic dose), the GABAergic agonist zolpidem 5 mg (the recommended dose in the elderly), or placebo. Balance (body sway measured by platform stability) and psychomotor performance (measured by choice reaction time) were assessed predose and at 1.5, 4, and 8 hours postdose in each period. Memory (measured by word recall) was assessed predose and at 4 hours postdose. FINDINGS/RESULTS: At 1.5 hours after nighttime administration of each drug (the approximate time of their anticipated maximal plasma concentrations), both zolpidem and suvorexant increased body sway versus placebo, with a greater increase for zolpidem than suvorexant. Suvorexant increased choice reaction time compared with placebo or zolpidem at 1.5 hours. There were no treatment differences on body sway or choice reaction time at 4 or 8 hours, or on word recall at 4 hours. IMPLICATIONS/CONCLUSIONS: These exploratory data suggest that a 30-mg dose of suvorexant (supratherapeutic) and a 5-mg dose of zolpidem (recommended dose in the elderly) impaired balance at 1.5 hours in healthy elderly people, with potentially less impairment for suvorexant relative to zolpidem, but no treatment differences on body sway or psychomotor performance at 4 and 8 hours. Because of their exploratory nature, these findings and their clinical relevance, if any, require confirmation in a prospective study.

Bumetanide prevents diazepam-modified anxiety-like behavior in lipopolysaccharide-treated mice.

Benzodiazepine receptor agonists are widely prescribed therapeutic agents that alter gamma-aminobutyric acid (GABA)A receptor activity and have anxiolytic effects. Post-operative use of benzodiazepines is a risk factor of delirium. Inflammatory conditions alter the anxiolytic effects of benzodiazepine. We investigated the effect of diazepam, a typical benzodiazepine anxiolytic, on changes in the emotional behavior of mice in a hole-board test after lipopolysaccharide (LPS) treatment. Diazepam dose-dependently increased the number of head-dips at doses that did not alter locomotor activity; however, diazepam dose-dependently significantly decreased the number of head-dips at doses that did not alter locomotor activity in LPS-treated mice. Flumazenil, a benzodiazepine receptor antagonist, normalized the decrease in head-dipping behavior caused by diazepam treatment in normal and LPS-treated mice. The decrease of the head-dipping effect caused by diazepam was attenuated by minocycline in LPS-treated mice. We further found that the decrease in head-dipping behavior caused by diazepam was blocked by bumetanide, a Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) antagonist, in LPS-treated mice. These findings suggest that diazepam induces the anxiety-like behavior under inflammation conditions, and may cause the GABAA receptor dysfunction associated with the chloride plasticity mediated by NKCC1, which contributes to benzodiazepine-induced delirium after surgery.

Driving performance assessments for benzodiazepine receptor agonist-related impairment: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to identify, map, and characterize the evidence for assessments that measure driving performance in people taking benzodiazepine receptor agonists. INTRODUCTION: Benzodiazepines and Z-drugs are widely prescribed for the treatment of anxiety disorders and insomnia even though they are not recommended as an initial treatment for these indications. Benzodiazepine and Z-drug use is associated with an elevated risk of traffic accidents, and guidance documents instruct patients to consult with their health care providers for instructions on how to safely operate a motor vehicle while consuming these medications. However, little is known about the assessments that measure driving performance regarding the extent and length of impairment from the consumption of the individual benzodiazepines and Z-drugs. INCLUSION CRITERIA: Eligible studies will include participants who are new, intermittent, or chronic users of benzodiazepines and Z-drugs. No exclusions will be applied regarding the health status of participants or whether their benzodiazepine and Z-drug use is for an approved indication as indicated by government agencies (eg, Health Canada) or practice guidelines. Studies that examine the consumption of a benzodiazepine and Z-drug in association with the operation of a motor vehicle (real or simulated) with direct or indirect objective or standard subjective measures or indicators of impairment while operating a motor vehicle will be considered. METHODS: Embase (Elsevier), MEDLINE (Ovid), and PsycINFO (EBSCO) will be searched as sources of published studies. Only studies published in English will be included, and there will be no limit on dates of publication. After screening the titles and abstracts of identified citations, two independent reviewers will retrieve potentially relevant full-text studies and extract data. Data will be presented in diagrammatic or tabular form accompanied by a narrative summary.

New pharmacologic agents for insomnia and hypersomnia.

PURPOSE OF REVIEW: Insomnia and hypersomnia are conditions with multifactorial causes that can be difficult to treat. There have been recent developments and changes in the treatment of both conditions, including the addition of some agents that have a novel mechanism of action. This review summarizes recent changes and highlights pertinent updates. RECENT FINDINGS: Benzodiazepine receptor agonists received a warning in 2019 regarding the possibility of complex sleep behaviors, such as sleepwalking. Zolpidem has been marketed in new dosage forms that include sublingual tablets and oral spray formulations. Orexin receptor antagonists appear to be well tolerated with a good safety profile. Suvorexant received an approval for the treatment of patients with comorbid insomnia and dementia. Lemborexant was demonstrated to be effective for maintenance insomnia. Trazodone was shown to affect the oligomerization of tau proteins thus suggesting potential implications in attenuating dementia pathology. Pitolisant, a novel histamine-3 receptor antagonist/inverse agonist, gained approval for the treatment of excessive daytime sleepiness in adults with narcolepsy as well as obstructive sleep apnea. Solriamfetol, a new norepinephrine and dopamine reuptake inhibitor, was approved for hypersomnolence based on good efficacy, but with cardiovascular warnings. SUMMARY: Recent advancements in the treatment of insomnia includes agents with novel mechanisms, new indications, and new dosage forms. Risk of complex sleep behaviors, and possible next-day driving impairment, should be discussed for all agents used for insomnia, including orexin receptor antagonists. Novel agents also are available for hypersomnia and there are options beyond traditional stimulants that may have great utility.

Association of Hypnotic Drug Use with Fall Incidents in Hospitalized Elderly Patients: A Case-Crossover Study.

We investigated whether use of hypnotic drugs, including benzodiazepine receptor agonists, as well as ramelteon and suvorexant are associated with fall incidents in elderly inpatients aged no less than 75 years, who were hospitalized at an acute care general hospital in Japan, between November 1st, 2016 and October 31st, 2017. Multivariate analysis results were reported as odds ratio (OR) with 95% confidence interval (CI). Following to a case-crossover study protocol, the time windows of the case and the control days were assigned to the day or the days, which are one day or 2-8 d before the fall incidents, respectively. In the enrolled 111 patients, the accumulated total available numbers of the cases and the control days were 111 and 554 patient days, respectively. Hypnotic drug use was significantly associated with fall incidents (OR: 2.85, 95% CI: 1.03-7.90, p = 0.04). Especially benzodiazepine receptor agonists (OR: 5.79, 95% CI: 1.52-22.1, p = 0.01) showed statistically significant association with fall incidents. In contrast, neither ramelteon (OR: 7.95, 95% CI: 0.72-87.9, p = 0.09) nor suvorexant (OR: 0.25, 95% CI: 0.06-1.06, p = 0.06) were significantly associated with fall incidents. Thus, benzodiazepine receptor agonists, but not ramelteon or suvorexant, showed significant association with fall incidents. Therefore, special care should be taken especially when benzodiazepine receptor agonists are administrated to elderly subjects. In contrast, fall risk may be much less in patients treated with ramelteon or suvorexant. These results could help us to conduct safer drug treatment for insomnia patients aged no less than 75 years.

[Effect of Digital Labels on Electronic Medical Records for Reducing the Use of Benzodiazepine Receptor Agonists].

Benzodiazepine receptor agonists (BZDs) should be appropriately used owing to the associated risks of delirium and falls. Since January 2018, the liaison team pharmacist at Iizuka Hospital has been applying digital labels with recommendations for the reduction of use and changes in the medication orders and prescriptions of BZDs on electronic medical records of patients in the surgical ward. This study aimed to verify the effectiveness of reducing the use of BZDs via the implementation of digital labels. Patients in the surgical ward were retrospectively assessed for changes in medication orders and prescription ratios of BZDs before and after the implementation of digital labels. The ratio of the number of digital labels implemented to the number of confirmations of medication orders and prescriptions of BZDs was 15.0% at the start of implementation; however, the ratio gradually and significantly decreased to 3.6%. The medication order ratio of BZDs was 52.2% before the implementation of digital labels; however, this ratio decreased to 2.7% and 5.6% immediately and 4 months after the implementation of digital labels, respectively. The present study showed that medication orders for BZDs were reduced after the implementation of digital labels and that the reduction effect was maintained for a certain period of time. Thus, the liaison team pharmacist-led approach can contribute to the proper use of BZDs.

[Effectiveness of Pharmacist-convened Multidisciplinary Clinical Team Meetings in Promoting Appropriate Benzodiazepine Receptor Agonist Use].

Benzodiazepine receptor agonists (BZRAs) are used in the treatment of a wide variety of clinical conditions. Although clinical practice guidelines discourage high dosage or long-term use of BZRAs, they are prescribed in clinical settings. This study aimed to investigate whether the pharmacists at multidisciplinary clinical team meetings can help reduce BZRA use and promote appropriate use of these drugs. The psychiatric unit of the Tokyo Women's Medical University Hospital occupies two floors, with 31 beds on Floor A and 34 beds on Floor B. The multidisciplinary clinical team meetings were held once a week in each ward. During the meetings, the pharmacists comprehensively assessed the number of BZRA doses administered and the equivalent diazepam doses, presented their prescription recommendations aimed at dosage reduction, and shared their views with the entire clinical team. This intervention was commenced on Floor A in 2014 and on Floor B in 2015. The average number of BZRAs in each period and equivalent diazepam doses were assessed for 273 psychiatric inpatients hospitalized from April to June in 2013, 2014, and 2015. Changes in the number of BZRA doses administered were assessed per floor per year. The results showed a statistically significant decrease between years with and without interventions. The intervention of pharmacists allowed multidisciplinary clinical team members to gain the same understanding about BZRA use and formulation of drug therapy plans. The results suggest that the intervention of pharmacists at clinical team meetings can strategically lead to decreased BZRA dosages and their proper use.

Photosensitive epilepsy: Robust clinical efficacy of a selective GABA potentiator.

OBJECTIVE: The objective of this phase 2a study was to assess the activity of PF-06372865, a positive allosteric modulator (PAM) of α2/3/5 subunit-containing GABAA receptors with minimal activity at α1-containing receptors, which are believed to mediate many of the adverse events associated with benzodiazepines, in the epilepsy photosensitivity model as a proof-of-principle of efficacy. METHODS: Seven participants with a photoparoxysmal response to intermittent photic stimulation (IPS) at baseline were randomized in a double-blind, 4-period cross-over study examining single doses of 17.5 and 52.5 mg PF-06372865, 2 mg lorazepam (active control), and placebo. Standardized photosensitivity ranges (SPRs) to IPS were recorded at screening, predose, and 1, 2, 4, and 6 hours postdose. The primary endpoint was the average least squares mean change in the SPR in the participant's most sensitive eye condition, across all time points. RESULTS: Both doses of PF-06372865 produced a marked and statistically significant mean reduction in SPR compared to placebo, which was similar in degree to lorazepam. There was complete suppression of SPR in 6/7 participants following PF-06372865 or lorazepam administration. PF-06372865 was safe and well-tolerated. CONCLUSION: PF-06372865 demonstrated highly robust efficacy. This demonstrates anticonvulsant activity of a novel α2/3/5-subtype selective GABAA PAM in humans. Further study of the antiepileptic properties of PF-06372865 is warranted. CLINICALTRIALSGOV IDENTIFIER: NCT02564029. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for people with a stable photoparoxysmal response to intermittent photic stimulation, PF-06372865 reduces the SPR.

[Association between Elimination Half-life of Benzodiazepines and Falls in the Elderly: A Meta-analysis of Observational Studies].

Benzodiazepine receptor agonists (BZDRAs) have been associated with an increased risk of falls in the elderly. However, the association between the elimination half-life (t1/2) of BZDRAs and the difference between benzodiazepines (BZDs) and non-benzodiazepines (Z-drugs) has not been clarified. By conducting a meta-analysis of observational studies, we compared the risk of falls with respect to 1) short-acting BZDRAs (t1/2<12 h) vs. long-acting BZDRAs (t1/2≥12 h) and 2) BZDs vs. Z-drugs in elderly patients. Data were retrieved from MEDLINE, the Cochrane Library, and Igaku Chuo Zasshi. In total, 13 observational studies from 12 articles were included in our study (short-acting BZDRAs, n=12; long-acting BZDRAs, n=9; BZDs, n=13; Z-drugs, n=7). The risk of falls was significantly increased by the use of short-acting BZDRAs [Odds ratio (OR) (95% Confidence interval (CI)): 2.00 (1.46-2.73)], long-acting BZDRAs [OR (95%CI): 2.16 (1.61-2.89)], BZDs [OR (95%CI): 1.67 (1.31-2.13)], and Z-drugs [OR (95%CI): 2.42 (1.35-4.34)] compared to the risk in BZDRAs non-users. The increased risk of falls in elderly patients was similar in each group and unrelated to t1/2. This study suggested that all BZDRAs including Z-drugs should be avoided in elderly patients.

MIDD0301 - A first-in-class anti-inflammatory asthma drug targets GABAA receptors without causing systemic immune suppression.

We report a 28-day repeat dose immunotoxicity evaluation of investigational drug MIDD0301, a novel oral asthma drug candidate that targets gamma amino butyric acid type A receptors (GABAA R) in the lung. The study design employed oral administration of mice twice daily throughout the study period with 100 mg/kg MIDD0301 mixed in peanut butter. Compound dosing did not reveal signs of general toxicity as determined by animal weight, organ weight or haematology. Peanut butter plus test drug (in addition to ad libitum standard rodent chow) did not affect weight gain in the adult mice, in contrast to weight loss in 5 mg/kg prednisone-treated mice. Spleen and thymus weights were unchanged in MIDD0301-treated mice, but prednisone significantly reduced the weight of those organs over the 28-day dosing. Similarly, no differences in spleen or thymus histology were observed following MIDD0301 treatment, but prednisone treatment induced morphological changes in the spleen. The number of small intestine Peyer's patches was not affected by MIDD0301 treatment, an important factor for orally administered drugs. Circulating lymphocyte, monocyte and granulocyte numbers were unchanged in the MIDD0301-treated animals, whereas differential lymphocyte numbers were reduced in prednisone-treated animals. MIDD0301 treatment did not alter IgG antibody responses to dinitrophenyl following dinitrophenyl-keyhole limpet haemocyanin immunization, indicating that systemic humoral immune function was not affected. Taken together, these studies show that repeated daily administration of MIDD0301 is safe and not associated with adverse immunotoxicological effects in mice.

Benzodiazepine and opioid co-usage in the US population, 1999-2014: an exploratory analysis.

STUDY OBJECTIVES: The study objectives were to explore trends in prevalence of couse of benzodiazepine receptor modulators and opioids, and nonselective and selective (i.e. Z-drugs) benzodiazepine receptor modulators, in the United States, as well as risk factors for these drug utilization patterns. METHODS: This was a multiyear, cross-sectional, population-level study, using US health survey data. Data from eight National Health and Nutrition Examination Survey (NHANES) cycles were analyzed, from 1999-2000 until 2013-2014, with each survey cycle containing information on ~10 000 individuals. The main measure was prevalent prescription drug use within 30 days preceding survey administration. Drug usage was objectively confirmed for a large majority of participants though direct inspection of prescription bottles. RESULTS: The estimated prevalence of concurrent benzodiazepine receptor modulator and opioid use in the United States was 0.39% in 1999-2000 and 1.36% in 2013-2014, reflecting absolute and relative changes of +0.97% and +249%. The estimated prevalence of nonselective and selective benzodiazepine receptor modulator couse steadily rose in the United States from 0.05% in 1999-2000 to 0.47% in 2013-2014, reflecting absolute and relative increases of +0.42% and +840%. Independent risk factors for these two forms of psychoactive medication polypharmacy were identified. CONCLUSIONS: In this exploratory analysis, concurrent use of benzodiazepine receptor modulators and opioids, and nonselective and selective benzodiazepine receptor modulators, was found to have progressively risen in the United States. The progressive increases in these two forms of psychoactive medication polypharmacy are concerning, given that these drug use patterns are associated with increased risk for serious adverse outcomes.

Zolpidem related persistent genital arousal disorder: An interesting case.

The present paper is describing a case of persistent genital arousal disorder that developed to a 55-year-old woman, shortly after the initiation of zolpidem. Persistent genital arousal disorder (PGAD) is a clinical entity that appears with a relatively low frequency in women, and is characterized by persistent or recurrent, unwanted and bothersome feelings of genital arousal, which often do not resolve with orgasm and are not associated with sexual desire (sexual interest, thoughts or fantasies). Women who experience PGAD often have feelings of shame, guilt and distress. Although its exact etiology remains unclear, various etiological factors have been proposed, central or peripheral, which may be psychological, vascular, dietary, pharmacological or neurological. Additionally, its presence has been associated to restless legs syndrome and overactive bladder syndrome. Likewise, multiple therapeutic interventions have been proposed and tried in patients with PGAD, either pharmacological (SSRIs, SNRIs, antiandrogens, benzodiazepines, antipsychotics, anticonvulsive agents) or other (ECT, physiotherapy, psychotherapy, nerve stimulation). Zolpidem is a nonbenzodiazepine indirect GABA A receptor agonist, which has lately been used as a therapeutic agent for PGAD in some cases. Nevertheless, in our patient, receiving zolpidem for insomnia seemed to be timely connected to the onset of PGAD symptomatology. The aim of the present paper is to highlight the need for more research into the possible factors that may contribute to PGAD.

Self-efficacy for deprescribing: A survey for health care professionals using evidence-based deprescribing guidelines.

BACKGROUND: Although polypharmacy is associated with significant morbidity, deprescribing can be challenging. In particular, clinicians express difficulty with their ability to deprescribe (i.e. reduce or stop medications that are potentially inappropriate). Evidence-based deprescribing guidelines are designed to help clinicians take action on reducing or stopping medications that may be causing more harm than benefit. OBJECTIVES: Determine if implementation of evidence-based guidelines increases self-efficacy for deprescribing proton pump inhibitor (PPI), benzodiazepine receptor agonist (BZRA) and antipsychotic (AP) drug classes. METHODS: A deprescribing self-efficacy survey was developed and administered to physicians, nurse practitioners and pharmacists at 3 long-term care (LTC) and 3 Family Health Teams in Ottawa, Canada at baseline and approximately 6 months after sequential implementation of each guideline. For each drug class, overall and domain-specific self-efficacy mean scores were calculated. The effects of implementation of each guideline on self-efficacy were tested by estimating the difference in scores using paired t-test. A linear mixed-effects model was used to investigate change over time and over practice sites. RESULTS: Of eligible clinicians, 25, 21, 18 and 13 completed the first, second, third and fourth survey respectively. Paired t-tests compared 14 participants for PPI and BZRA, and 9 for AP. Overall self-efficacy score increased for AP only (95% confidence intervals (CI) 0.32 to 19.79). Scores for domain 2 (develop a plan to deprescribe) increased for PPI (95% CI 0.52 to 24.12) and AP guidelines (95% CI 2.46 to 18.11); scores for domain 3 (implement the plan for deprescribing) increased for the PPI guideline (95% CI 0.55 to 14.24). Longitudinal analysis showed an increase in non-class specific scores, with a more profound effect for clinicians in LTC where guidelines were routinely used. CONCLUSION: Implementation of evidence-based deprescribing guidelines appears to increase clinicians' self-efficacy in developing and implementing a deprescribing plan for specific drug classes.

The Use of Benzodiazepine Receptor Agonists and the Risk of Hospitalization for Pneumonia: A Nationwide Population-Based Nested Case-Control Study.

BACKGROUND: The relationship between the use of benzodiazepine-receptor agonists (BZRAs) and the risk of hospitalization for pneumonia remains inconclusive. This study aimed to explore the association between BZRA use and hospitalization for pneumonia in a general population. METHODS: This population-based nested case-control study used Taiwan's National Health Insurance Research Database between 2002 and 2012. We included only new users who did not have any BZRA prescriptions on record in the preceding 2 years and identified 12,002 subjects who were hospitalized for pneumonia (International Classification of Diseases, Ninth Revision codes 480-486, and 507) and 12,002 disease risk score-matched control subjects. A logistic regression model was used to determine the association of BZRA use and hospitalization for pneumonia. The exposure date, dose-response relationship, and class of BZRAs were comprehensively assessed. RESULTS: Current BZRA exposure was associated with hospitalization for pneumonia (adjusted OR [aOR],1.86; 95% CI, 1.75-1.97). Benzodiazepine hypnotic agents (aOR, 2.42; 95% CI, 2.16-2.71) had a higher risk of pneumonia than did benzodiazepine anxiolytic agents (aOR, 1.53; 95% CI, 1.44-1.63) or nonbenzodiazepine hypnotic agents (aOR, 1.60; 95% CI, 1.46-1.76). The pneumonia risk was increased with ultrashort-acting and short- to intermediate-acting agents, a higher defined daily dose, and the number of BZRAs used. Among individual BZRAs examined, midazolam had a higher risk (aOR, 5.77; 95% CI, 4.31-7.73) of hospitalization for pneumonia than did the others. CONCLUSIONS: This study suggests that there is a dose-response relationship between current BZRA use and the risk of hospitalization for pneumonia. In addition, benzodiazepine hypnotic agents, especially midazolam, present a greater risk of hospitalization for pneumonia. These findings reinforce the importance of a careful analysis of the benefits vs the risks of BZRA use.