Benzodiazepine-related Drugs Research Articles

Is general practitioner involvement in the initiation of opioids for chronic non-cancer pain associated with opioid dose and concurrent drug use?

Objective Is the involvement of the regular general practitioner (GP) in the decision to initiate opioid treatment for chronic non-cancer pain (CNCP) associated with two main risk factors for serious adverse events: increased opioid dose and the concomitant use of prescribed benzodiazepines or benzodiazepine-related medications? Design and setting An anonymous web-based survey was conducted in the county of Rogaland, Norway, during the spring of 2021. Subjects GPs who self-reported applying at least once for reimbursement of opioids prescribed to treat CNCP. They were asked to answer the survey based on the last patient for whom they recalled submitting a reimbursement application. Main outcome measures 1) Total opioid dose in daily oral morphine equivalents (OMEQ). 2) Concurrent use of benzodiazepines and/or benzodiazepine-related drugs. Results The daily opioid dose was lower when the surveyed GPs initiated the opioid treatment (36 OMEQ, n = 25), than when others had initiated the treatment (108 OMEQ, n = 31, p = 0.001). For concurrent use of benzodiazepine or benzodiazepine-related drugs, no significant difference was found (33%, n = 9 with GP involvement vs. 47%, n = 16, p = 0.279 with no GP involvement). Conclusions GP involvement in the initiation of opioid medication for CNCP was associated with a lower opioid dose being prescribed. Implications GP involvement in the initiation of opioid prescriptions may facilitate safer prescribing.

The COVID-19 pandemic and the use of benzodiazepines and benzodiazepine-related drugs in Estonia: an interrupted time-series analysis

BackgroundThe COVID-19 pandemic has posed challenges that worsened people’s mental health. We explored the impact of the COVID-19 pandemic on the mental well-being of the population, as indicated by the prevalence rates of benzodiazepine and benzodiazepine-related drug (BDZ) use.MethodsThis population‐based, time‐series analysis included all prescriptions of BDZs dispensed in Estonia between 2012 and 2021. The monthly prevalence rates of BDZ use were calculated. Autoregressive integrated moving average models with pulse and slope intervention functions tested for temporary and long-term changes in monthly prevalence rates after the onset of the COVID-19 pandemic.ResultsThroughout the 10-year study period, a total of 5,528,911 BDZ prescriptions were dispensed to 397,436 individuals. A significant temporary increase in the overall prevalence rate of BDZ use in March 2020 (2.698 users per 1000, 95% CI 1.408–3.988) was observed, but there was no statistically significant long-term change. This temporary increase affected all the examined subgroups, except for new users, individuals aged 15–29 years, and prescribing specialists other than general practitioners and psychiatrists. The long-term increase in BDZ use was confined to females aged 15–29 years (0.056 users per 1000 per month, 95% CI 0.033–0.079), while no significant change was observed among males of the same age (0.009 users per 1000 per month, 95% CI – 0.017 to 0.035). Among females aged 15–29 years, a significant long-term increase in BDZ use was observed for anxiety disorders (0.017 users per 1000 per month, 95% CI 0.010–0.023), depressive disorders (0.021 users per 1000 per month, 95% CI 0.012–0.030), and other mental and behavioral disorders (0.020 users per 1000 per month, 95% CI 0.010–0.030), but not for sleep disorders (– 0.008 users per 1000 per month, 95% CI – 0.018–0.002).ConclusionThe COVID-19 pandemic led to a short-term increase in BDZ use immediately after the pandemic was declared. In the long term, young females experienced a sustained increase in BDZ use. The prolonged effect on girls and young women suggests their greater vulnerability. These results underscore the need to effectively address the long-term effects of the pandemic among youth.

New users of anxiolytics and sedatives in Sweden-Drug type, doses, prescribers' characteristics, and psychiatric comorbidity in more than 750,000 patients.

Anxiety and sleep disorders are common in the population and anxiolytics and sedatives are widely used. Our aim was to describe the drug utilization of new users of anxiolytics and sedatives in adults including type of drug, doses, prescribers' characteristics, and psychiatric comorbidity. A register-based cohort study of new users (18-64years) of anxiolytics and sedatives in 2015-2019, free of any such drug 5years prior to inclusion. The individuals were linked to national registers on dispensed drugs and recorded diagnoses. In total, 764,432 new users of anxiolytics and sedatives were identified, which corresponds to an incidence of 26/1000 inhabitants and year. The proportion of new users of benzodiazepines (including both anxiolytics and sedatives) decreased, whereas the proportion of sedative antihistamines and melatonin increased. The most common drug dispensed was hydroxizin (33%) followed by benzodiazepine related drugs (zopiclone and zolpidem; 20%), propiomazine (14%) and benzodiazepines (13%). The majority (68%) of the prescriptions were from primary care. Most new users were prescribed 1-30DDDs and 52% among women and 49% among men were dispensed their drug only once during the first year. Half of the new users had a previous comorbid psychiatric disorder. The findings are well reflecting the recommendations in national guidelines.

Patterns of filled prescriptions and the association with risk of drug-induced death. A population-based nested case-control register study.

Opioid analgesics (OA) and other pharmaceuticals have been associated with drug-induced deaths. However, there is a lack of knowledge regarding patterns of use of these pharmaceuticals in the population and regarding such associations. We identify and describe subgroups of people with different patterns of filled prescriptions of OA and other relevant pharmaceuticals and examine associations with drug-induced deaths. In addition, we estimate the proportion of drug-induced deaths with a filled OA prescription and OA as cause of death. A Norwegian population-based nested case-control register study with cases (drug-induced deaths 2010-2018, N = 2388) and population controls matched for age, gender and year of inclusion (N = 21 465). Patterns of filled prescriptions for opioid analgesics (OA), benzodiazepines and benzodiazepine-related drugs, gabapentinoids, ADHD medication and antidepressants/antipsychotics were explored by k-means cluster analysis. Associations with drug-induced deaths were estimated by conditional logistic regression adjusted for sociodemographic characteristics. Overlap of filled OA prescriptions and OA as cause of death was estimated. Five clusters were identified: 'few prescriptions', 'weak OA', 'ADHD medication', 'sedative/psychiatric morbidity' and 'strong OA'. The 'strong OA' cluster had higher socioeconomic status compared to the other groupings. The risk of drug-induced death was also highest in this cluster (OR = 35.5; CI 25.6-49.3) and, for 68% (CI 64-73) of cases, filled prescriptions for OA was indicated as the underlying cause of death. The cluster analysis identified a subgroup with filled prescriptions of OA and other pharmaceuticals and a higher socioeconomic status than other subgroups. This subgroup had a high risk of drug-induced death that needs to be addressed.

The association of benzodiazepine and benzodiazepine-related drugs with outcomes after surgery for colorectal cancer

Benzodiazepines increase plasma brain-derived neurotrophic factor (BDNF) level which, in turn, may improve survival in colorectal cancer (CRC) patients. This study aimed to evaluate the associations between benzodiazepine and benzodiazepine-related drugs (BZRD) use and outcomes of patients operated for CRC. This is a retrospective cohort study including patients operated for CRC at Limoges’ University Hospital between 2010 and 2019. Data were collected from two sources: medical records of patients in the digestive, general and endocrine surgery department at Limoges University Hospital and from the Haute-Vienne general cancer registry. Patients were divided into benzodiazepine users and non-users. Outcomes were overall survival (OS) and recurrence-free survival (RFS). Among 504 patients who underwent surgery for CRC, 125 (24.8%) patients were treated with benzodiazepine/BZRD drugs. Users and non-users of benzodiazepine/BZRD showed no statistically significant differences in 5-year OS (45.5 ± 1.9% vs. 46.5 ± 1.1% p = 0.25) and 5-year RFS (41.0 ± 2.1% vs. 39.6 ± 1.3%, p = 0.94), even after adjustment for confounders and propensity score (OS: aHR=1.02, 95%CI: 0.71–1.48; RFS: aHR=1.00, 95%CI: 0.72–1.40). Subgroup analysis on CRC patients with psychiatric disorders revealed that benzodiazepine users had better RFS (aHR=0.58, 95%CI: 0.35–0.96) compared with non-users, particularly, patients with stages III or IV of CRC had better OS (aHR=0.27; 95%CI: 0.12–0.59) and RFS (aHR=0.30, 95%CI: 0.15–0.62). OS and RFS was significantly better in patients taking benzodiazepines classified as anxiolytics, having longer half-life, and producing active metabolites. In conclusion, benzodiazepine use was not associated with outcomes in CRC patients. Nevertheless, in subgroup of patients with psychiatric disorders and advanced CRC stage, benzodiazepine could improve survival.

Long-Term Use of Benzodiazepines and Benzodiazepine-Related Drugs: A Register-Based Danish Cohort Study on Determinants and Risk of Dose Escalation.

The authors investigated the frequency and determinants of long-term use and risk of dose escalation of benzodiazepines and benzodiazepine-related drugs (benzodiazepine receptor agonists, or BZRAs). All adults ages 20-80 years living in Denmark on January 1, 2000 (N=4,297,045) were followed for redeemed prescriptions of BZRAs in the Danish National Prescription Registry from January 1, 2000, to December 31, 2020. For each drug class, we calculated long-term use for more than 1 or 7 years, and dose escalation measured as increase in dose to a level above the recommended level. Associations were examined using logistic regression. The authors identified 950,767 incident BZRA users, of whom 15% and 3% became long-term users for more than 1 or 7 years, respectively. These percentages were highest for individuals who initiated Z-drugs (17.8% and 4%). Among the 5% of BZRA users who had at least 3 years of continuous use, there was no indication of dose escalation, as the median dose remained relatively stable. However, 7% (N=3,545) of BZRA users escalated to doses above the recommended level. Psychiatric comorbidity, especially substance use disorder, was associated with higher risk of long-term use and dose escalation. A limited portion of the population that received BZRA prescriptions were classified as continuous users, and only a small proportion of this group escalated to doses higher than those recommended in clinical guidelines. Thus, this study does not, under the current regulations, support the belief that BZRA use frequently results in long-term use or dose escalation.

Prescription high-risk polysubstance use among opioid maintenance treatment patients.

Among individuals receiving buprenorphine or methadone as opioid maintenance treatment (OMT), concomitant use of other central nervous system depressants, including prescription drugs, can increase risk of overdose. We aimed to 1) determine the prevalence of use of high-risk prescription drugs (opioid analgesics, benzodiazepines, benzodiazepine-related drugs, and gabapentinoids) among OMT patients, 2) calculate its associations with different mental health and pain-related diagnoses, and 3) compare prevalence of concomitant use with the general population. A national sample comprising all individuals filling at least one prescription of OMT drugs in Norway in 2019 was formed. Healthcare registry data were linked to investigate high-risk prescription drug use and different diagnoses. We calculated one-year prevalence of use, amount dispensed in defined daily doses (DDDs), and the number of prescribers for the different high-risk prescription drugs. Logistic regression was used to determine associations (adjusted odds ratios; aOR, 95% confidence intervals (CIs)) between diagnoses and use. Prevalence of use was calculated both in the OMT patient sample and the general population. Among the OMT patient sample (n=7,299), 47.6% (n=3,476) filled prescriptions for benzodiazepines. For each high-risk prescription drug group, there was a median of 1-2 prescribers. Musculoskeletal diagnoses were the strongest factor for concomitant high-risk prescription drug use for both males (aOR 3.23, CI: 2.72-3.85) and females (aOR 3.07, CI: 2.42- 3.90). The 1-year prevalence of benzodiazepine use was 11.4 times higher for males and 7.1 times higher for females in OMT than the general population. The amount in DDDs was higher for every drug for OMT patients than the general population, particularly for benzodiazepines. OMT patients frequently filled prescriptions for high-risk drugs, and in higher dosages than the general population. However, we found little evidence of 'doctor shopping.' Given that these prescription drugs carry overdose risk, particularly when combined with OMT drugs, our findings emphasize the continued need for education and caution to both prescribers and patients on their concomitant use with OMT.

Long-term use of benzodiazepines and benzodiazepine-related drugs, a register-based danish cohort study on determinants and risk of dose escalation

Long-term use of benzodiazepines and benzodiazepine-related drugs, a register-based danish cohort study on determinants and risk of dose escalation

Sedative drug-use in Denmark, 2000 to 2019: a nationwide drug utilization study.

To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs. In this descriptive study, we used individual prescription data on the entire Danish population from the Danish National Prescription Registry to calculate yearly incidence and prevalence of use of benzodiazepines, benzodiazepine-related drugs (Z-drugs), melatonin, olanzapine, low-dose quetiapine, mianserin/mirtazapine, pregabalin, and promethazine from 2000 through 2019. From the Danish National Patient Registry, we obtained data on drug users' psychiatric and somatic comorbidity. The use of benzodiazepines and Z-drugs declined gradually from 2000 through 2019, whereas the newer alternatives, melatonin, low-dose quetiapine, pregabalin and promethazine, increased in use, while the use of olanzapine and mianserin/mirtazapine was relatively stable. This development was seen in both men and women and across all age groups except for hypnotic benzodiazepines which showed a steep increase in the oldest age group from 2010. For all sedative drugs depression, anxiety, alcohol and misuse disorder, pain and cancer were the most prevalent comorbidities. During our study period, the number of individuals without any of the selected diagnoses increased. In Denmark different central regulations have influenced prescription practice toward more restrictive use of Z-drugs and benzodiazepines, except for hypnotic benzodiazepine prescriptions increased after the introduction of special palliative care. An increase in use of newer sedative drugs, however, indicates that the regulations do not remove the need for sedative drugs in the population.

Drug checking services as a surveillance tool for clinical laboratories: Examining trends in the unregulated fentanyl supply

ObjectivesTimely assessment and understanding of drug trends is essential for clinical laboratories to effectively respond to the overdose epidemic. In this proof-of-concept study, we sought to determine whether information obtained through Toronto’s Drug Checking Services (DCS) and cross-provincial urine drug testing (UDT) data can be used as a surveillance tool for clinical laboratories and discuss the value of collaboration between the clinical laboratory, clinicians, and community partners to optimize patient care. Design & MethodsMass spectrometry-based UDT data from LifeLabs Ontario (n = 127,529) and British Columbia (n = 14,848), and drug checking data from Toronto DCS (n = 3,308 drugs or used paraphernalia) was collected between August 2020 and October 2021. Fentanyl co-positivity with toxic adulterants such as benzodiazepine-related drugs and fentanyl analogues were examined. ResultsThe percent co-positivity of fentanyl with etizolam, flualprazolam, flubromazolam, carfentanil, and acetylfentanyl in both Ontario UDT and DCS drugs/used paraphernalia showed similar trends. Regional differences in co-positivity with etizolam and fentanyl analogues were noted between Ontario and British Columbia UDT with patterns consistent over the entire 15-month collection period. ConclusionsClinical laboratories should connect with their local DCS, if available, to understand and monitor unregulated drug trends. These data can be used as an important tool to help clinical laboratories tailor their UDT menus and thereby provide a community-focused service to improve patient care.

Use of benzodiazepines and benzodiazepine-related drugs in the Nordic countries between 2000 and 2020.

Use of benzodiazepines (BZ) and related drugs is subject to considerable debate due to problems with dependency and adverse events. We aimed to describe and compare their use across the Nordic countries. Data on the use of clonazepam, BZ-sedatives, BZ-hypnotics, and benzodiazepine-related drugs (BZRD) in adults (≥20 years) were obtained from nationwide registers in Denmark, Finland, Iceland, Norway, and Sweden, 2000-2020. Main measures were therapeutic intensity (TI:DDD/1000 inhabitants [inhab.]/day) and annual prevalence (users/1000 inhab./year). Overall, TI of BZ and related drugs decreased in all Nordic countries from 2004 to 2020. However, there were considerable differences between countries in TI. In 2020, the TI of BZ and related drugs ranged from 17 DDD/1000 inhab./day in Denmark to 93 DDD/1000 inhab./day in Iceland. BZRD accounted for 55-78% of BZ use in 2020, followed by BZ sedatives at 20-44%, BZ-hypnotics at <1-5%, and clonazepam at <1-2%. Annual prevalence of BZ use increased with age in all countries, and the highest annual prevalence was observed among people ≥80 years. Overall, the use of BZ and related drugs has decreased in all Nordic countries from 2004 to 2020, however, with considerable differences in their use between countries. The highest prevalence was observed among the oldest age groups-despite warnings against their use in this population.

Trendovi u prometu i potrošnji antidepresiva i benzodiazepina u Republici Srbiji u periodu 2006-2019. godina

Introduction: Antidepressants and benzodiazepines are used for the pharmacological treatment of mental illness with complementary therapies, with their global use showing an increasing trend. Aim: The aim of the study is to examine trends in the use of antidepressants and benzodiazepines in Serbia for the period 2006-2019. Method: Annual data on consumption were taken from the Serbian Medicines Agency and expressed in defined daily doses per 1000 inhabitants per day (DDD / TID). Consumption trends were analysed using segmented regression. Segmented regression calculates the average annual percentage change (AAPC) in consumption during the observed period from 2006 to 2019. Results: Consumption of antidepressants and benzodiazepines in 2019 were 35 DDD / TID and 126 DDD / TID, with percentage increases of 360% and 33% compared to 2006 and with AAPC values of 11.8 (p &lt; 0.001) and 0.7 (p = 0.564) respectively. Among antidepressants, selective serotonin reuptake inhibitors were the most widely used. Anxiolytics-derivatives of benzodiazepines (N06BA) were the most used group among benzodiazepines. Bromazepam and Lorazepam had the highest volume in the N06BA group. Benzodiazepine-related drugs (Zolpidem) also had a growing trend, especially from 2006 to 2009. Conclusion: Use of benzodiazepines and antidepressants in Serbia increased, following global trends.

Automated multi-dose dispensing in persons with and without Alzheimer\u2019s disease\u2014impacts on pharmacotherapy

PurposeWe investigated the drug use before and after transition to automated multi-dose dispensing (MDD) service among persons with Alzheimer’s disease (AD) and compared whether the changes were similar in persons without AD.MethodsThe register-based Finnish nationwide MEDALZ cohort includes 70,718 community-dwelling persons diagnosed with AD during 2005–2011. Each person who initiated MDD was matched in both groups with a comparison person without MDD by age, gender and for persons with AD, also time since AD diagnosis at the start of MDD. The study cohort included 15,604 persons with AD in MDD and 15,604 no-MDD, and 5224 persons without AD in MDD and 5224 no-MDD. Point prevalence of drug use was assessed every 3 months, from 1 year before to 2 years after the start of MDD and compared between persons in MDD to those who did not have MDD.ResultsMDD was started on average 2.9 (SD 2.1) years after AD diagnosis. At the start of MDD, the prevalence of drug use increased especially for antipsychotics, antidepressants, opioids, paracetamol and use of ≥ 10 drugs among persons with and without AD. Prevalence of benzodiazepine use (from 12% 12 months before to 17% at start of MDD), memantine (from 29 to 46%) and ≥ 3 psychotropics (from 3.2 to 6.0%) increased among persons with AD. Decreasing trend was observed for benzodiazepine-related drugs, urinary antispasmodics and non-steroidal anti-inflammatory drugs.ConclusionMDD seems to be initiated when use of psychotropics is initiated and the number of drugs increases.

Pneumonia Risk Associated with the Use of Individual Benzodiazepines and Benzodiazepine Related Drugs among the Elderly with Parkinson's Disease.

Most patients with Parkinson’s disease (PD) gradually develop oropharyngeal dysphagia which is often associated with pneumonia risk. The possible association of benzodiazepine (BZD) and benzodiazepine related drugs (BZRD) use with pneumonia risk has received increasing attention but remains controversial. We investigated pneumonia risk associated with the use of BZDs and BZRDs in older adult patients with PD. This case-control study analyzed data of 551,975 older adult patients with PD between 2001 and 2018 in Taiwan. To minimize potential confounding, we used 1:4 propensity score matching to include older adult patients without pneumonia as controls. Incident pneumonia risk was significantly higher in current (adjusted odds ratio (aOR) = 1.25, 95% CI = 1.23–1.27) and past (aOR = 1.13, 95% CI = 1.11–1.15) users of BZDs. Regarding BZRDs, recent (aOR = 1.08, 95% CI = 1.06–1.11) and past (aOR = 0.89, 95% CI = 0.88–0.91) users had higher and lower risks of incident pneumonia, respectively. Pneumonia risk varied based on their use of BZDs and BZRDs. In these individuals, incident pneumonia risk was high in users of BZDs, such as midazolam, lorazepam, flunitrazepam, estazolam, and clonazepam. Regarding the use of BZRDs, zopiclone increased incident pneumonia risk.

Improving drug prescription in general practice using a novel quality improvement model

Introduction Quality improvement (QI) clusters have been established in many countries to improve healthcare using the Breakthrough Series’ collaboration model. We investigated the effect of a novel QI approach based on this model of performed medication reviews and drug prescription in a Norwegian municipality. Methods All 27 General Practitioners (GPs) in a mid-size Norwegian municipality were invited to join the intervention, consisting of three peer group meetings during a period of 7–8 months. Participants learned practical QI skills by planning and following up QI projects within drug prescription practice. Evaluation forms were used to assess participants’ self-rated improvement, reported medication review reimbursement codes (MRRCs) were used as a process measure, and defined daily doses (DDDs) of potentially inappropriate drugs (PIDs) dispensed to patients aged 65 years or older were used as outcome measures. Results Of the invited GPs, 25 completed the intervention. Of these, 76% self-reported improved QI skills and 67% reported improved drug prescription practices. Statistical process control revealed a non-random increase in the number of MRRCs lasting at least 7 months after intervention end. Compared with national average data, we found a significant reduction in dispensed DDDs in the intervention municipality for benzodiazepine derivates, benzodiazepine-related drugs, drugs for urinary frequency and incontinence and non-steroid anti-inflammatory and antirheumatic medications. Conclusion Intervention increased the frequency of medication reviews, resulting in fewer potentially inappropriate prescriptions. Moreover, there was self-reported improvement in QI skills in general, which may affect other practice areas as well. Intervention required relatively little absence from clinical practice compared with more traditional QI interventions and could, therefore, be easier to implement. KEY POINT The current study investigated to what extent a novel model based on the Breakthrough Series’ collaborative model affects GP improvement skills in general practice and changes their drug prescription. KEY FINDINGS Most participants reported better improvement skills and improved prescription practice. The number of dispensed potentially inappropriate drugs decreased significantly in the intervention municipality compared with the national average. The model seemed to lead to sustained changes after the end of the intervention.

Long-Term Real-World Effectiveness of Pharmacotherapies for Schizoaffective Disorder.

ObjectiveTo investigate the long-term real-world effectiveness of antipsychotics and other psychopharmacotherapies in the treatment of schizoaffective disorder (SCHAFF). MethodTwo nationwide cohorts of SCHAFF patients were identified from Finnish and Swedish registers. Within-individual design was used with stratified Cox regression. The main exposure was use of antipsychotics. Adjunctive pharmacotherapies included mood stabilizers, antidepressants, and benzodiazepines and benzodiazepine-related drugs. The main outcome was hospitalization due to psychosis. ResultsThe Finnish cohort included 7655 and the Swedish cohort 7525 patients. Median follow-up time was 11.2 years (IQR 5.6–11.5) in the Finnish and 7.6 years (IQR 3.8–10.3) in the Swedish cohort. Clozapine and long-acting injectable (LAI) antipsychotics were consistently associated with a decreased risk of psychosis hospitalization and treatment failure (psychiatric hospitalization, any change in medication, death) in both cohorts. Quetiapine was not associated with a decreased risk of psychosis hospitalization. Mood stabilizers used in combination with antipsychotics were associated with a decreased risk of psychosis hospitalization (Finnish cohort HR 0.76, 95% CI 0.71–0.81; Swedish cohort HR 0.84, 0.78–0.90) when compared with antipsychotic monotherapy. Combination of antidepressants and antipsychotics was associated with a decreased risk of psychosis hospitalization in the Swedish cohort (HR 0.90, 0.83–0.97) but not in the Finnish cohort (1.00, 0.94–1.07), and benzodiazepine use was associated with an increased risk (Finnish cohort HR 1.07, 1.01–1.14; Swedish cohort 1.21, 1.13–1.30). ConclusionsClozapine, LAIs, and combination therapy with mood stabilizers were associated with the best outcome and use of quetiapine and benzodiazepines with the worst outcome in the treatment of SCHAFF.

Trends in the consumption rates of benzodiazepines and benzodiazepine-related drugs in the health region of Lleida from 2002 to 2015

BackgroundThe high prevalence and long-term use of benzodiazepines (BZDs) treatment are debated topics because of the risk they can cause to the patients. Despite the current information on the risk-benefit balance of these drugs, their consumption remains particularly high. We determined the trend in the consumption prevalence of benzodiazepines (BZDs) and drugs related to BZDs (Z-drugs) in the population of the Health Region of Lleida to explore patterns of use and the associated characteristics associated between 2002 and 2015.MethodsAn analysis of secular trends was carried out between 2002 and 2015; the databased included all individuals from the Health Region of Lleida, which had 358,157 inhabitants in 2015, that consumed BZDs. The consumption of BZDs was evaluated using prescription billing data from the Public Health System. All types of BZDs and BZD analogues that had been approved by the drug agency were included. Trends by age and sex were investigated.ResultsOver the whole study period, a total of 161,125 individuals accounted for 338,148 dispensations. Overall, 59% were women, and the mean age was 56 years. The dispensing prevalence of BZDs use in 2015 was 14.2% overall —18.8% in women and 9.6% in men—and was 36% in those over 65 years. According to the half-life of BZDs, the prevalence of short-intermediate BZD use, intermediate-long BZD use, and Z-drugs use was 9.7, 5.5 and 0.8%, respectively. The evolution of the annual prevalence of BZD dispensing showed a progressive decline, from 15.3% in 2002 to 14.2% in 2015, which was attributed to a decrease in the consumption of intermediate-long half-life BZDs (8.0% vs. 5.5%) and Z-drugs (1.4% vs. 0.8%).ConclusionThe dispensing prevalence of BZDs and Z-drugs was high, although a small reduction was observed during this time period. The dispensing prevalence was especially high in the population over 65, despite the risk of cognitive decline and falls. Integral actions are required to lower the BZD prescription rate.

Prescription patterns of benzodiazepine and benzodiazepine-related drugs in the peripartum period: A population-based study

Using prescription drugs during pregnancy is challenging and approached with caution. In this study, we present population-based information on prescription patterns of benzodiazepines and benzodiazepine-related drugs in the peripartum period. A population-based study of 1,154,817 pregnancies between 1997 and 2015 in Denmark, of which 205,406 (17.8%) pregnancies in women with a psychiatric history. Prescription drugs starting with Anatomical Therapeutic Chemical codes N05BA, N05CD, and N05CF from 12 months before pregnancy to 12 months following pregnancy were identified. We used generalised estimating equations to estimate the adjusted 5 year risk difference in the proportion of women redeeming benzodiazepines from 1 year to 5 years after. Logistic regression was used to analyze the association between characteristics and discontinuation of benzodiazepines during pregnancy. The prevalence of benzodiazepine prescriptions was 1.9% before pregnancy, 0.6% during pregnancy, and 1.3% after pregnancy. In women with a psychiatric history, the prevalence was 5–6 times higher. A significant decrease in prescriptions to women with a psychiatric history was observed, which was less profound among women with no psychiatric history. Approximately 90% of women discontinue benzodiazepines during pregnancy, with a higher percentage of women discontinuing from 1997 to 2015. The observed decrease is likely explained by changing treatment guidelines.

Psychotropic Drug-Associated Pneumonia in Older Adults.

The use of psychotropic drugs (antipsychotics, benzodiazepines and benzodiazepine-related drugs, and antidepressants) is common, with a prevalence estimates range of 19–29% among community dwelling older adults. These drugs are often prescribed for off-label use, including neuropsychiatric symptoms. The older adult population also has high rates of pneumonia and some of these cases may be associated with adverse drug events. In this narrative review, we summarize the findings from current observational studies on the association between psychotropic drug use and pneumonia in older adults. In addition to studies assessing the use of psychotropics, we included antiepileptic drugs, as they are also central nervous system-acting drugs, whose use is becoming more common in the aging population. The use of antipsychotics, benzodiazepine, and benzodiazepine-related drugs are associated with increased risk of pneumonia in older adults (≥ 65 years of age), and these findings are not limited to this age group. Minimal and conflicting evidence has been reported on the association between antidepressant drug use and pneumonia, but differences between study populations make it difficult to compare findings. Studies regarding antiepileptic drug use and risk of pneumonia in older persons are lacking, although an increased risk of pneumonia in antiepileptic drug users compared with non-users in persons with Alzheimer’s disease has been reported. Tools such as the American Geriatric Society Beers Criteria and the STOPP/START criteria for potentially inappropriate medications aids prescribers to avoid these drugs in order to reduce the risk of adverse drug events. However, risk of pneumonia is not mentioned in the current criteria and more research on this topic is needed, especially in vulnerable populations, such as persons with dementia.

Benzodiazepines or related drugs and risk of pneumonia: A systematic review and meta-analysis.

Benzodiazepines and benzodiazepine-related drugs (BZRDs) are used to treat various psychiatric diseases. However, there are concerns that BZRDs increase the risk of pneumonia. We performed a systematic review and meta-analysis of observational studies to determine whether BZRD use affects the risk of pneumonia. Our analysis included all observational studies that compared pneumonia development among patients receiving BZRD vs those with no treatment. In total, 12 citations of 10 studies involving more than 120,000 pneumonia cases were included in our meta-analysis. After pooling the estimates, the odds for developing pneumonia were 1.25-fold higher (odd ratio, OR=1.25; 95% confidence interval (CI), 1.09-1.44) in BZRD users compared with individuals who had not taken BZRD. On the basis of exposure window, we found an increased risk of pneumonia among current (OR=1.4; 95%CI, 1.22-1.6) and recent (OR=1.38; 95%CI, 1.06-1.8) users, but not with the past users (OR=1.11; 95%CI, 0.96-1.27). Current or recent exposure to BZRD is associated with an increased pneumonia risk. Clinicians need to weight the benefit-risk balance of BZRD use, especially those with other risk factors for pneumonia.