Real or fake? Sourcing and marketing of non-prescribed benzodiazepines amongst two samples of people who regularly use illicit drugs in Australia.

INTRODUCTION: There is concern around non-prescribed benzodiazepine use, particularly with increasing detections of counterfeit products containing high-risk novel compounds. The aims of this study were to investigate how and which non-prescribed benzodiazepines are being sourced; forms, appearance and packaging; and awareness of risks associated with non-prescribed benzodiazepines. METHODS: Data were collected from a sample of Australians who inject drugs or use ecstasy and/or other illicit stimulants on a monthly or more frequent basis, and who reported past 6-month use of non-prescribed benzodiazepines (n = 235 and n = 250, respectively). Data were collected on source, diversion from a known/trusted prescription, product name and aesthetic characteristics for the last non-prescribed benzodiazepine obtained. RESULTS: Amongst participants who injected drugs, 71% reported that their last non-prescribed benzodiazepines were diverted from a known/trusted prescription, compared to 59% of participants who used ecstasy/other stimulants. Sourcing via cryptomarkets was rare. Across both samples, the majority reported last obtaining substances sold/marketed as diazepam or alprazolam. Participants sourcing via non-diverted means were twice as likely to obtain alprazolam. Known sourcing of novel compounds was rare. Amongst participants who used ecstasy/other stimulants, 36% reported confidence in the content/dose of non-prescribed benzodiazepines even when the source is unknown. DISCUSSION AND CONCLUSIONS: Most participants obtained substances sold as classic/registered benzodiazepines, mostly via diverted prescriptions, with a substantial minority potentially unaware of counterfeits circulating. While diverted use undeniably presents risks, tightening of prescriptions in Australia could inadvertently lead to greater supply of novel benzodiazepines as seen internationally, reinforcing prioritisation of demand and harm reduction strategies.

[Standardization of Hypnotic Agents for Prevention of Falls: A Pharmacoeconomic Study].

To reduce the number of falls caused by hypnotic agents, the standardization of insomnia treatment was carried out at Yamaguchi University Hospital from April 2019. There were concerns that medical costs would increase due to the selected medicines-suvorexant and eszopiclone-being more expensive than conventional benzodiazepines. In this study, the standardization of insomnia treatment was evaluated by pharmacoeconomics. The costs of the hypnotic agents was considered, as was the cost of examination/treatment following falls. Effectiveness was evaluated as the incidence of falls within 24 hours of taking hypnotic agents. This analysis took the public healthcare payer's perspective. Propensity score matching based on patient background, showed that, per hospitalization the medicine costs of the recommended group increased by 1,020 yen, however, the examination/treatment costs following falls decreased by 487 yen when compared with the non-recommended group. Overall, the recommended group incurred costs of 533 yen more per hospitalization for patients prescribed hypnotic agents compared to the non-recommended group, but the incidence of falls for the recommended group was significantly lower than that in the non-recommended group (1.9% vs. 6.3%; p<0.01). These results suggest that in order to prevent the incidence of falls by 1 case, it is necessary to increase costs by 12,086 yen which is the subthreshold cost for switching to the recommended medicine as standardization. The selection of recommended medicines may be a cost-effectiveness option compared with non-recommended medicines.

Association Between Preoperative Benzodiazepine Use and Postoperative Opioid Use and Health Care Costs.

Importance: The association between preoperative benzodiazepine use and long-term postoperative outcomes is not well understood. Objective: To characterize the association between preoperative benzodiazepine use and postoperative opioid use and health care costs. Design, Setting, and Participants: In this cohort study, retrospective analysis of private health insurance claims data on 946 561 opioid-naive patients (no opioid prescriptions filled in the year before surgery) throughout the US was conducted. Patients underwent 1 of 11 common surgical procedures between January 1, 2004, and December 31, 2016; data analysis was performed January 9, 2020. Exposures: Benzodiazepine use, defined as long term (≥10 prescriptions filled or ≥120 days supplied in the year before surgery) or intermittent (any use not meeting the criteria for long term). Main Outcomes and Measures: The primary outcome was opioid use 91 to 365 days after surgery. Secondary outcomes included opioid use 0 to 90 days after surgery and health care costs 0 to 30 days after surgery. Results: In this sample of 946 561 patients, the mean age was 59.8 years (range, 18-89 years); 615 065 were women (65.0%). Of these, 23 484 patients (2.5%) met the criteria for long-term preoperative benzodiazepine use and 47 669 patients (5.0%) met the criteria for intermittent use. After adjusting for confounders, long-term (odds ratio [OR], 1.59; 95% CI, 1.54-1.65; P < .001) and intermittent (OR, 1.47; 95% CI, 1.44-1.51; P < .001) benzodiazepine use were associated with an increased probability of any opioid use during postoperative days 91 to 365. For patients who used opioids in postoperative days 91 to 365, long-term benzodiazepine use was associated with a 44% increase in opioid dose (additional 0.6 mean daily morphine milligram equivalents [MMEs]; 95% CI, 0.3-0.8 MMEs; P < .001), although intermittent benzodiazepine use was not significantly different (0.0 average daily MMEs; 95% CI, -0.2 to 0.2 MMEs; P = .65). Preoperative benzodiazepine use was also associated with increased opioid use in postoperative days 0 to 90 for both long-term (32% increase, additional 1.9 average daily MMEs; 95% CI, 1.6-2.1 MMEs; P < .001) and intermittent (9% increase, additional 0.5 average daily MMEs; 95% CI, 0.4-0.6 MMEs; P < .001) users. Intermittent benzodiazepine use was associated with an increase in 30-day health care costs ($1155; 95% CI, $938-$1372; P < .001), while no significant difference was observed for long-term benzodiazepine use. Conclusions and Relevance: The findings of this study suggest that, among opioid-naive patients, preoperative benzodiazepine use may be associated with an increased risk of developing long-term opioid use and increased opioid dosages postoperatively, and also may be associated with increased health care costs.

The burden of decisional uncertainty in the treatment of status epilepticus.

OBJECTIVE: Treatments for convulsive status epilepticus (SE) have a wide range of effectiveness. The estimated effectiveness of non-intravenous benzodiazepines (non-IV BZDs) ranges from approximately 70% to 90% and the estimated effectiveness of non-benzodiazepine antiseizure medications (non-BZD ASMs) ranges from approximately 50% to 80%. This study aimed to quantify the clinical and economic burden of decisional uncertainty in the treatment of SE. METHODS: We performed a decision analysis that evaluates how decisional uncertainty on treatment choices for SE impacts hospital admissions, intensive care unit (ICU) admissions, and costs in the United States. We evaluated treatment effectiveness based on the available literature. RESULTS: Use of a non-IV BZD with high estimated effectiveness, like intranasal midazolam, rather than one with low estimated effectiveness, like rectal diazepam, would result in a median (p25 -p75 ) reduction in hospital admissions from 6 (3.9-8.8) to 1.1 (0.7-1.8) per 100 cases and associated cost reductions of $638 ($289-$1064) per pediatric patient and $1107 ($972-$1281) per adult patient. For BZD-resistant SE, use of a non-BZD ASM with high estimated effectiveness, like phenobarbital, rather than one with low estimated effectiveness, like phenytoin/fosphenytoin, would result in a reduction in ICU admissions from 9.1 (7.3-11.2) to 3.9 (2.6-5.5) per 100 cases and associated cost reduction of $1261 ($445-$2223) per pediatric patient and $319 ($-93-$806) per adult patient. Sensitivity analyses showed that relatively minor improvements in effectiveness may lead to substantial reductions in downstream hospital admissions, ICU admissions, and costs. SIGNIFICANCE: Decreasing decisional uncertainty and using the most effective treatments for SE may substantially decrease hospital admissions, ICU admissions, and costs.

A comparison of trends in opioid dispensing patterns between Medicaid pharmacy claims and prescription drug monitoring program data.

PURPOSE: Public and private payers have implemented benefit limitations to reduce high-risk opioid prescriptions. The effect of these policies on the increase of out-pocket payment is unclear. To understand this gap, we compared the discrepancies in trends between opioid prescription fills vs claims among Medicaid beneficiaries. METHODS: Data from the Oregon Prescription Drug Monitoring Program (PDMP) and Oregon Medicaid administrative claims were used to identify Medicaid beneficiaries 18 years and older enrolled at least one full month from 2015 to 2017. Generalized linear models assessed the trends in the monthly rates of opioid PDMP prescription fills and pharmacy claims per 1000 eligible members. Rates by morphine equivalent dose (MED) tier (<50, 50-89, 90-120, >120 MED) and co-prescribed opioid and benzodiazepine were also assessed. RESULTS: During the study period, an average of 495 355 Medicaid members had 2 797 054 opioid PDMP fills and 2 472 155 opioid Medicaid pharmacy claims. Study participants had 15.4 (95% confidence interval [CI] 13.6 to 17.0; P < .001) more prescriptions per 1000 member per month in the PDMP data (114.1 [SD 7.4]) compared with the Medicaid claims data (98.7 [SD 7.9]). Similarly, there were 1.9 more co-occurring opioid/benzodiazepine prescriptions per 1000 members per month observed in the PDMP data than the Medicaid claims data (95% CI 1.7 to 2.1; P < .001). At each MED tier, the PDMP fills were consistently higher than the claims (P < .001). CONCLUSIONS: Higher rate of fills in the PDMP compared to pharmacy claims suggests that there may be an increasing trend of out-of-pocket payment among Medicaid beneficiaries.

[Need for Prescription Suggestions for Long-term Inpatients in the Psychiatric Ward].

Additional fees for ward pharmacists' services have been valued for hospitals in Japan. However, the calculation period for services provided to inpatients in the psychiatric ward is limited to 8 weeks. This study aimed to reveal the need for the services of pharmacists in the hospital ward for inpatients hospitalized for >8 weeks in the psychiatric ward. Patients who were hospitalized in the psychiatric ward from September 2016 to February 2017 were analyzed retrospectively. The pharmacists suggested prescriptions for inpatients admitted for >8 weeks, similar to those admitted for <9 weeks, and this supported pharmacotherapy without exacerbating patient outcomes. Moreover, significant decreases in benzodiazepine doses were found between the prior and post prescription suggestions of the pharmacist for inpatients >8 weeks of admission. Healthcare expenditures were also reduced. These results suggest that the prescriptions suggested by pharmacists for inpatients admitted for >8 weeks in the psychiatric ward were useful. In conclusion, our findings show that ward pharmacists' services were necessary not only for the inpatients hospitalized for <9 weeks, but also for those hospitalized for >8 weeks.

Prescription Benzodiazepine Use in Privately Insured U.S. Children and Adolescents.

INTRODUCTION: Benzodiazepines are commonly prescribed in the U.S. but entail safety concerns, including dependency. In pediatrics, many indications lack trial data. Authors aimed to describe youth initiating prescription benzodiazepine treatment, identify potential indications and prescribing concerns, estimate the duration of treatment by potential indication, and identify factors that predict long-term use. METHODS: The study cohort included children (aged 3-12 years) and adolescents (aged 13-17 years) initiating prescription benzodiazepine treatment (≥3 days' supply) from January 2010 to September 2015 in a U.S. commercial claims database. Potential indications included selected ICD-9-CM diagnoses (≤30 days prior). Long-term (≥6 months) benzodiazepine treatment was estimated with Kaplan-Meier estimation and modified Poisson regression identified independent predictors of long-term benzodiazepine treatment (analysis completed in 2018). RESULTS: Of 24,504 children and 61,046 adolescents initiating benzodiazepines, 62% of the children and 68% of the adolescents had a potential indication. Anxiety disorders were the most common indication, with mental health indications more common among adolescents (45%) than children (23%) and epilepsy and movement disorders higher in children. Recent opioid prescriptions were common before benzodiazepine initiation (children, 22%; adolescents, 21%). Six percent of the initiators became long-term benzodiazepine users. Potential indication, provider contact, psychotropic medication, and chronic conditions independently predicted long-term benzodiazepine treatment in adolescents and children. CONCLUSIONS: U.S. children and adolescents are prescribed benzodiazepines for various mental health and other medical conditions, many lacking evidence of pediatric efficacy. Long-term benzodiazepine treatment, concurrent opioid prescriptions, psychotropic use, and prior substance use disorder diagnoses suggest safety risks among some youth prescribed benzodiazepines.

Effect of reimbursement restriction policy on the use of benzodiazepines in the Netherlands: an interrupted time series analysis.

OBJECTIVES: Use of benzodiazepines has health risks. Reimbursement was restricted in the Netherlands from January 2009 onwards with the goal to reduce chronic use and healthcare expenditures. The aim of this study is to assess the initial and long-term effects of this policy on benzodiazepine use. DESIGN: Interrupted time series analysis, segmented regression models, Kaplan-Meier survival analysis and Cox proportional hazards analysis. SETTING: A 10% random sample of benzodiazepine dispensings by outpatient pharmacies between January 2002 and August 2015 were obtained from the PHARMO database. This database covered a catchment area representing about 3.6 million residents in 2015. PARTICIPANTS: 2 500 800 benzodiazepine prescriptions from 128 603 patients were included. INTERVENTION: Reimbursement restriction policy from January 2009 onwards. OUTCOME MEASURES: Changes in: the volume of dispensed prescriptions and doses, the incidence, prevalence of incidental, regular and chronic use and discontinuation rates of benzodiazepines. RESULTS: The volume of dispensed prescriptions and doses decreased by 12.5% (95% CI 9.0% to 15.9%) and 15.1% (95% CI 11.4% to 17.3%) respectively in January 2009 compared with December 2008. A clear initial effect on the overall incidence (-14.7%; 95% CI -19.8% to 9.6%) and the prevalence of incidental (-17.8%; 95% CI -23.9% to 11.7%), regular (-20.0%; 95% CI -26.1% to 13.9%) and chronic (-16.0%; 95% CI -23.1% to 8.9%) use was observed. A statistically significant reduction in the monthly trend per 1000 medication users was observed for the overall incidence (-0.017; 95% CI -0.031 to 0.003) and the prevalence of incidental (-3.624; 95% CI -4.996 to 2.252) but not for regular (-0.304; 95% CI -1.204 to 0.596) and chronic (0.136; 95% CI -0.858 to 1.130) use. Patients who started treatment before policy had a slightly higher probability of discontinuation (HR=1.013; 95% CI 1.004 to 1.022). CONCLUSIONS: The reimbursement policy had a significant initial effect on the volume, incidence and prevalence of benzodiazepine use. In addition, there is a statistically significant reduction in the monthly trend of overall incidence and of the prevalence of incidental use. No statistically significant reduction in the monthly trend of chronic use, the main purpose of the reimbursement restriction, could be demonstrated.

Association of Opioid, Anti-Depressant, and Benzodiazepines With Workers' Compensation Cost: A Cohort Study.

BACKGROUND: Antidepressants, benzodiazapines, and opioid medications are used to manage the pain, anxiety, or depression associated with workplace injuries. OBJECTIVE: To evaluate the impact of these medications on workers' compensation costs and time lost from work. METHODS: A cohort of 22,383 indemnity claims from 2008 to 2013 were evaluated for the association of prescribed medications on claim cost and delayed claim closure controlling for confounders. RESULTS: Claims with anti-depressant, opioid, or benzodiazepine prescriptions were 2.24 (95% CI: 2.00 to 2.51), 1.14 (95% CI: 1.02 to 1.27), and 1.38 (95% CI: 1.23 to 1.54) times more likely to remain open at the end of the study. CONCLUSION: The concurrent treatment of pain, depression or anxiety, and occupational injuries are associated with large increases in claim cost and delayed return to work.

Economic impact of potentially inappropriate prescribing and related adverse events in older people: a cost-utility analysis using Markov models.

OBJECTIVES: To determine the economic impact of three drugs commonly involved in potentially inappropriate prescribing (PIP) in adults aged ≥65 years, including their adverse effects (AEs): long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines and proton pump inhibitors (PPIs) at maximal dose; to assess cost-effectiveness of potential interventions to reduce PIP of each drug. DESIGN: Cost-utility analysis. We developed Markov models incorporating the AEs of each PIP, populated with published estimates of probabilities, health system costs (in 2014 euro) and utilities. PARTICIPANTS: A hypothetical cohort of 65 year olds analysed over 35 1-year cycles with discounting at 5% per year. OUTCOME MEASURES: Incremental cost, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios with 95% credible intervals (CIs, generated in probabilistic sensitivity analysis) between each PIP and an appropriate alternative strategy. Models were then used to evaluate the cost-effectiveness of potential interventions to reduce PIP for each of the three drug classes. RESULTS: All three PIP drugs and their AEs are associated with greater cost and fewer QALYs compared with alternatives. The largest reduction in QALYs and incremental cost was for benzodiazepines compared with no sedative medication (€3470, 95% CI €2434 to €5001; -0.07 QALYs, 95% CI -0.089 to -0.047), followed by NSAIDs relative to paracetamol (€806, 95% CI €415 and €1346; -0.07 QALYs, 95% CI -0.131 to -0.026), and maximal dose PPIs compared with maintenance dose PPIs (€989, 95% CI -€69 and €2127; -0.01 QALYs, 95% CI -0.029 to 0.003). For interventions to reduce PIP, at a willingness-to-pay of €45 000 per QALY, targeting NSAIDs would be cost-effective up to the highest intervention cost per person of €1971. For benzodiazepine and PPI interventions, the equivalent cost was €1480 and €831, respectively. CONCLUSIONS: Long-term benzodiazepine and NSAID prescribing are associated with significantly increased costs and reduced QALYs. Targeting inappropriate NSAID prescribing appears to be the most cost-effective PIP intervention.

Impact of Differences in Economic Development and Socioeconomic Stability on Benzodiazepine Exposure between the Three Balkans Countries.

INTRODUCTION: Anxiety disorders are among the most common mental disorders. Benzodiazepines belong to the group of anxiolytic sedatives and the most prescribed drugs in the world. The aim in ours study was to evaluate the differences in the exposure of the population to benzodiazepines (in period from 2014-2018) between Serbia, Slovenia and Croatia, the three countries of the Southwestern Balkans with varying degrees of socioeconomic development. STUDY DESIGN: A academic investigator initiated, pharmacoepidemiological difference-in-difference time series analysis of population exposure to benzodiazepines between the three, geographically close Balkans countries (Slovenia, Serbia, Croatia) with varying degrees of socioeconomic development has been carried out. Study was conducted as academic investigator initiated, in a retrospective manner on monthly basis international data set from January 2014 to December 2018. RESULTS: At the annual level, during the study period from January 2014 to December 2018, compared to Slovenia, Serbia and Croatia had higher DIDs, from 5 fold (Croatia) to 6 fold (Serbia), for all benzodiazepines in total. By analyzing the differences-in-difference, we have shown that influence of both time (month) and country on DIDs is significant as well as their mutual interaction (the country x month) for all benzodiazepines in total. CONCLUSION: Serbia and Croatia must implement explicit measures of reducing benzodiazepine prescription in health primary care based on evidence-based recommendations in the indications where general medicine practitioners/family doctors most commonly prescribe these medicines. Without providing a realistic supplement/alternative to benzodiazepines such as increasing the availability of psychotherapy and improving the structure of psychiatric professionals in healthcare settings, implicit measures are not recommended for reducing prescription, implementing accountability measures for prolonged prescription of benzodiazepines, and in particular for "masked" somatic diseases. All this comes to the fore by raising economic development and socioeconomic stability.

County and Physician Variation in Benzodiazepine Prescribing to Medicare Beneficiaries by Primary Care Physicians in the USA.

BACKGROUND: Physicians widely prescribe benzodiazepines (BZD) despite well-recognized harms. OBJECTIVE: To determine county and provider characteristics that predict high-intensity BZD prescribing by primary care physicians (PCPs) to Medicare beneficiaries. DESIGN: Cross-sectional analysis of the 2015 Medicare Part D Public Use Files (PUF). SUBJECTS: n = 122,054 PCPs who prescribed 37.3 billion medication days. MAIN MEASURES: Primary outcome was intensity of BZD prescribing (days prescribed/total medication days) at the county- and physician levels. PCP and county characteristics were derived from the Part D PUF, Area Health Resources Files, and County Health Rankings. Logistic regression determined the characteristics associated with high-intensity (top quartile) BZD prescribing. KEY RESULTS: Beneficiaries were prescribed over 1.2 billion days of BZD in 2015, accounting for 2.3% of all medication days prescribed in Part D. Top quartile counties had 3.1 times higher BZD prescribing than the lowest (3.4% vs. 1.1%; F = 3293.8, df = 3, p < 0.001). Adjusting for county-level demographics and health care system characteristics (including supply of mental health providers), counties with more adults with at least some college had lower odds of high-intensity prescribing (per 5% increase, adjusted odds ratio [AOR] 0.80, 99% confidence interval (CI) 0.73-0.87, p < 0.001), as did higher income counties (per US$1000 increase, AOR 0.93, CI 0.91-0.95, p < 0.001). Top quartile PCPs prescribed at 6.5 times the rate of the bottom (3.9% vs. 0.6%; F = 63,910.2, df = 3, p < 0.001). High-intensity opioid prescribing (AOR 4.18, CI 3.90-4.48, p < 0.001) was the characteristic most strongly associated with BZD prescribing. CONCLUSIONS: BZD prescribing appears to vary across counties and providers and is related to non-patient characteristics. Further work is needed to understand how such non-clinical factors drive variation.

Decreasing Seizure Treatment Time Through Quality Improvement Reduces Critical Care Utilization.

BACKGROUND: Rapid, effective treatment for status epilepticus reduces associated morbidity and mortality, yet medication delivery remains slow in many hospitalized patients. We utilized quality improvement (QI) methodology to improve treatment times for hospitalized children with status epilepticus. We hypothesized rapid initial seizure treatment would decrease seizure morbidity. METHODS: We utilized QI and statistical process control analysis in a nonintensive care setting within a tertiary care pediatric hospital. We performed Plan-Do-Study-Act cycles including (1) revising the nursing process for responding to seizures, (2) emphasizing intranasal midazolam over intravenous lorazepam, (3) relocating medications and supplies, (4) developing documentation tools and reinforcing correct processes, (5) developing and disseminating an online education module for residents and nurse practitioners, and (6) completing standardization to intranasal midazolam. RESULTS: Seventeen months after starting the project, 66 seizures had been treated with a benzodiazepine in a median (p25-p75) time of 7.5 minutes (5 to 10), decreased from a baseline of 14 minutes (8-30) (P = 0.01). The proportion of patients receiving a benzodiazepine in 10 minutes or less improved from 39% to 79%. The proportion of patients transferred to intensive care decreased from a baseline of 39% to 9% (P < 0.005), resulting in an estimated $2.1 million in mitigated hospital charges. Significant harm did not occur during the implementation of these interventions. CONCLUSIONS: Children with status epilepticus were treated with benzodiazepines more rapidly and effectively following implementation of QI methodology. These interventions reduced utilization of critical care and mitigated hospital charges.

Assessment of the Availability, Cost, and Motivations for Use over Time of the New Psychoactive Substances-Benzodiazepines Diclazepam, Flubromazepam, and Pyrazolam-in the UK.

INTRODUCTION: There has been increasing interest in the availability of non-prescription benzodiazepines and their sale as new psychoactive substances. We wanted to determine UK availability from Internet suppliers and motivations for use of three benzodiazepines (diclazepam, flubromazepam, and pyrazolam). METHODS: In November 2014 and March 2016, using the European Monitoring Centre for Drugs and Drug Addiction Snapshot Methodology, Internet search engines ( google.co.uk , uk. yahoo.com and ask.com.uk ) were searched using the terms 'buy diclazepam', 'buy flubromazepam' and 'buy pyrazolam'. Threads from drug-user forums ( bluelight.org , drugs-forum.com , erowid.org , legalhighsforum.com ) were analysed using a general inductive approach. Data were converted into price per gram/pellet to allow cost comparisons and to determine motivations for use. RESULTS: There was an increase in websites selling these benzodiazepines between 2014 and 2016: diclazepam (49 in 2014 to 55 in 2016), pyrazolam (33 to 35), and flubromazepam (39 to 45). Thirty-eight (63.3%) sites were based in the UK/Europe. Drugs were sold as pellets (49 websites, 81.7%), powder (19, 31.7%), and blotters (1, 1.7%). Pill forms were not available, and one (1.7%) website sold diclazepam/flubromazepam in liquid form. The cost reduced with increasing purchase quantities. Main motivations for use included anxiolysis, management of benzodiazepine withdrawal, sedation/sleep aid, and management of stimulant withdrawal. CONCLUSIONS: These three benzodiazepines are widely available online, most commonly as pellets, and are (mis)used for a number of reasons. This study could be used to support triangulation of data from other sources to inform harm minimisation strategies.

Effect of total exemption from medical service co-payments on potentially inappropriate medication use among elderly ambulatory patients in a single center in Japan: a retrospective cross-sectional study.

OBJECTIVE: The effect of total exemption from medical service co-payments on drug prescribing practices has not been extensively evaluated. We conducted a retrospective cross-sectional study to evaluate the effect of total exemption from medical service co-payments on potentially inappropriate medication (PIM) and benzodiazepine use in elderly ambulatory patients. We defined PIM based on the Beers Criteria. RESULTS: Six hundred seventy-one consecutive patients aged 65 years or older who routinely visited internal medicine physicians were included. Their mean age was 75.7 years, and 342 (51.0%) patients were men. The proportions of patients taking any PIMs or benzodiazepines were 37.7% and 16.2%, respectively. Of all patients, 62 (9.2%) were totally exempt from medical service co-payments. The patients who were totally exempt from medical service co-payments showed a significantly increased risk of PIM (OR 2.16, 95% CI 1.28-3.66) or benzodiazepine use (OR 2.12, 95% CI 1.16-3.87) compared with patients who were not. These associations did not change after adjusting for age, gender, comorbidities and polypharmacy. These findings should be confirmed in other settings or hospitals in Japan.

Clinical and Economic Outcomes of Interventions to Reduce Antipsychotic and Benzodiazepine Use Within Nursing Homes: A Systematic Review.

BACKGROUND: Antipsychotic and benzodiazepine medications are widely used in nursing homes despite only modest efficacy and the risk of severe adverse effects. Numerous interventions have been implemented to reduce their use. However, the outcomes for the residents and staff and the economic impact on the healthcare system remain relatively understudied. OBJECTIVE: The aim was to examine the clinical and economic outcomes reported within interventions to reduce antipsychotic and/or benzodiazepine use in nursing homes. METHODS: Databases searched included PubMed, EMBASE, CINAHL, CENTRAL, Scopus, and ProQuest. We focussed on interventions with professional (e.g. education) and/or organisational (e.g. formation of multidisciplinary teams) components. Data were extracted from the papers that included clinical and/or economic outcomes. Two authors independently reviewed articles for eligibility and quality. RESULTS: Fourteen studies reported on clinical outcomes for the residents: 13 antipsychotic reduction studies and one study focussing exclusively on benzodiazepine reduction. There was substantial heterogeneity in the types of outcomes reported and the method of reporting. Change in behavioural and psychological symptoms was the most commonly reported outcome throughout the antipsychotic reduction interventions (n = 12 studies) and remained stable or improved in ten of 12 studies. Whilst improvements were seen in emotional responsiveness, measures of sleep, cognitive function, and subjective health score remained unchanged upon benzodiazepine reduction. No interventions included an economic analysis. CONCLUSIONS: Efforts should be made to improve the consistency in reporting of clinical outcomes within interventions to reduce antipsychotic and/or benzodiazepine medications. Additionally, the economic impact of these interventions should be considered. Nonetheless, evidence suggests that interventions that reduce antipsychotic use are unlikely to have deleterious clinical effects. The clinical and economic effects of benzodiazepine reduction remain under-reported.

Treatment Patterns, Health Care Resource Utilization, and Spending in Medicaid Beneficiaries Initiating Second-generation Long-acting Injectable Agents Versus Oral Atypical Antipsychotics.

PURPOSE: Second-generation long-acting injectable therapies (SGA-LAIs) may reduce health care resource utilization (HRU) and health care costs compared with daily oral atypical antipsychotics (OAAs) in patients with schizophrenia due to reduced dosing frequency, delivery/monitoring by a health care provider, and improved adherence. The aim of the present study was to compare treatment patterns, HRU, and Medicaid spending in patients with schizophrenia initiated on SGA-LAIs (overall and according to agent) versus OAAs. METHODS: Medicaid claims data (2010-2015) from 6 states were used to identify adult schizophrenia patients initiated on SGA-LAIs or OAAs. Treatment patterns (proportion of days covered [PDC] ≥80% and persistence [no gap ≥30, 60, or 90 days] to index treatment), HRU, and costs were evaluated over 12 months and compared by using multivariable logistic, Poisson, and ordinary least squares regression models, respectively. P values for HRU and cost outcomes were obtained from a nonparametric bootstrap procedure. Costs (2015 US dollars) reflect the Medicaid payer's perspective before any rebate. FINDINGS: Overall, 3307 and 21,355 patients initiated SGA-LAIs and OAAs, respectively (paliperidone palmitate LAI [PP-LAI; n = 2182], risperidone LAI [n = 968], aripiprazole LAI [n = 108], and olanzapine LAI [n = 49]). During follow-up and compared with OAA patients, SGA-LAI patients were more likely to reach PDC ≥80% (odds ratio [OR], 1.28; P < 0.001) and be persistent (eg, no gap ≥60 days; OR, 1.45; P < 0.001) to the index treatment. Relative to OAA patients, SGA-LAI patients had fewer long-term care days (incidence rate ratio [IRR], 0.75; P < 0.001) and home care visits (IRR, 0.75; P < 0.001) but more mental health institute (IRR, 1.16; P < 0.001) and 1-day mental health institute (IRR, 1.16; P < 0.001) admissions. Moreover, PP-LAI patients had fewer inpatient days (IRR, 0.78; P = 0.004) versus OAA patients. SGA-LAI patients had lower medical costs (mean monthly cost difference [MMCD], -$168; P < 0.001) than OAA patients, offsetting more than one half of the higher pharmacy costs (MMCD, $271; P < 0.001). Compared with OAAs, only PP-LAI was associated with significant medical cost savings (MMCD, -$225; P < 0.001). IMPLICATIONS: Medicaid beneficiaries with schizophrenia initiated on SGA-LAIs had better adherence and persistence to therapy over 12 months than patients initiated on OAAs. SGA-LAIs, particularly PP-LAI, were associated with lower medical costs that successfully offset more than one half of the higher pharmacy costs relative to OAA.

Cost-effectiveness of 3-month paliperidone therapy for chronic schizophrenia in the Netherlands.

BACKGROUND: A new depot formulation of paliperidone has been developed that provides effective treatment for schizophrenia for 3 months (PP3M). It has been tested in phase-3 trials, but no data on its cost-effectiveness have been published. PURPOSE: To determine the cost-effectiveness of PP3M compared with once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT), risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating chronic schizophrenia in The Netherlands. METHODS: A previous 1-year decision tree was adapted, based on local inputs supplemented with data from published literature. The primary analysis used DRG costs in 2016 euros from the insurer perspective, as derived from official lists. A micro-costing analysis was also conducted. For the costing scenario, official list prices were used. Clinical outcomes included relapses (treated as outpatients, requiring hospitalization, total), and quality-adjusted life-years (QALYs). Rates and utility scores were derived from the literature. Economic outcomes were the incremental cost/QALY-gained or relapse-avoided. Model robustness was examined in scenario, 1-way, and probability sensitivity analyses. RESULTS: The expected cost was lowest with PP3M (8,781€), followed by PP1M (10,325€), HAL-LAT (11,278€), RIS-LAT (11,307€), and oral-OLZ (13,556€). PP3M had the fewest total relapses/patient (0.36, 0.94, 1.39, 1.21, and 1.70, respectively), hospitalizations (0.11, 0.46, 0.40, 0.56, and 0.57, respectively), emergency room visits (0.25, 0.48. 0.99, 0.65, and 1.14, respectively) and the most QALYs (0.847, 0.735, 0.709, 0.719, and 0.656, respectively). In both cost-effectiveness and cost-utility analyses, PP3M dominated all other drugs. Sensitivity analyses confirmed base case findings. In the costing analysis, total costs were, on average, 31.9% higher than DRGs. CONCLUSIONS: PP3M dominated all commonly used drugs. It is cost-effective for treating chronic schizophrenia in the Netherlands. Results were robust over a wide range of sensitivity analyses. For patients requiring a depot medication, such as those with adherence problems, PP3M appears to be a good alternative anti-psychotic treatment.