Real‐world evidence on the use of benzodiazepine receptor agonists and the risk of venous thromboembolism

Chen, Tien‐Yu; Winkelman, John W.; Mao, Wei; Tzeng, Nian Sheng; Kuo, Terry B.J.; Yang, Cheryl C.H.; Tsai, Hui Ju; Wu, Chi‐Shin

doi:10.1111/jth.15033

Cited by 8 publications

(4 citation statements)

References 39 publications

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“…Particularly, the number of benzodiazepine receptor agonists (BZRAs) prescriptions is high among hypnotics and anxiolytics in Japan [ 2 ]. Also, many studies reported adverse effects of BZRAs, such as falls and venous thromboembolism [ 3 , 4 ]. However, in recent years, hypnotics and anxiolytics or BZRAs prescription trends have not been revealed using nationwide statistics data.…”

Section: Introductionmentioning

confidence: 99%

Analysis of regional differences in the amount of hypnotic and anxiolytic prescriptions in Japan using nationwide claims data

Okui

Park

2022

BMC Psychiatry

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Background In Japan, there has been no investigation of regional differences in the number or amount of prescriptions of anxiolytics or hypnotics. Attributes related to the high amount of prescriptions for these drugs are unknown. We investigated recent trends and regional differences in the amount of prescriptions of hypnotics and anxiolytics in Japan and identified factors associated with these regional differences. Methods The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open data from 2015 to 2018 were used. We calculated diazepam-equivalent doses (mg) for each drug and the total amount of prescriptions per capita for hypnotics and anxiolytics by sex and age. In addition, we calculated the standardized claim ratio (SCR) of the amount of prescriptions by prefecture. We investigated factors associated with regional differences in the SCRs of hypnotics and anxiolytics using the prefectures’ medical, socioeconomic, and physical characteristics by an ecological study using a linear mixed-effects model. Results The amount of prescriptions of hypnotics and anxiolytics, specifically, the amount of prescriptions of benzodiazepine receptor agonists (BZRAs), decreased in many of the adult age groups from 2015 to 2018. The regression analysis revealed that the number of medical clinics per capita, the number of public assistance recipients per capita, the proportion of persons whose HbA1c ≥ 6.5%, and the proportion of persons whose BMI ≥25 kg/m2 were positively and significantly associated with the SCR of hypnosis. In contrast, the number of public assistance recipients per capita and the proportion of persons whose BMI ≥25 kg/m2 were positively and significantly associated with the SCR of anxiolytics. Conclusions Factors associated with prescription amount of hypnotics and anxiolytics were revealed in this study, and a further study is needed for investigating causal relationships between the prescriptions amount and the associated factors using individual data.

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Section: Introductionmentioning

confidence: 99%

Analysis of regional differences in the amount of hypnotic and anxiolytic prescriptions in Japan using nationwide claims data

Okui

Park

2022

BMC Psychiatry

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“…In addition to antipsychotics, several benzodiazepines had a positive, previously reported association. 43 Immobilization and sedation may be potential contributors to the thrombosis risk. All in all, thrombotic risk among patients with severe psychiatric disorders and psychotropic medications is important in clinical practice, and the threshold of adequate diagnostics should be low in cases of potential thrombotic symptoms.…”

Section: Discussionmentioning

confidence: 99%

A pharmacoepidemiological nested case-control study of risk factors for venous thromboembolism with the focus on diabetes, cancer, socioeconomic group, medications, and comorbidities

Myllylahti,

Niskanen,

Lassila

et al. 2024

Diabetes and Vascular Disease Research

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Objectives A pharmacoepidemiological study to assess VTE risk factors in a diabetes-rich population. Methods The study comprised 299,590 individuals. We observed 3450 VTEs and matched them with 15,875 controls using a nested case-control approach and collected data on comorbidities and prescriptions. By multivariable conditional logistic regression, we calculated ORs with 95%CIs for comorbidities and medications to evaluate their associations with VTE. Results Diabetes (aOR 2.16; 95%CI 1.99–2.34), inflammatory bowel disease (1.84; 1.27–2.66), and severe psychiatric disorders (1.72; 1.43–2.05) had the strongest associations among the non-cancer comorbidities. Pancreatic (12.32; 7.11–21.36), stomach (8.57; 4.07–18.03), lung and bronchus (6.26; 4.16–9.43), and ovarian (6.72; 2.95–15.10) cancers were ranked as high-risk for VTE. Corticosteroids, gabapentinoids, psychotropic drugs, risedronic acid, and pramipexole were most strongly associated (aOR exceeding 1.5) with VTE. Insulin (3.86; 3.33–4.47) and sulphonylureas (2.62; 2.18–3.16) had stronger associations than metformin (1.65; 1.49–1.83). Statins and lercanidipine (0.78; 0.62–0.98) were associated with a lowered risk of VTE. Conclusions In this cohort, with 50% diabetes prevalence, pancreatic, stomach, lung and bronchus, and ovarian cancers were strongly associated with VTE. Corticosteroids, gabapentinoids, and psychotropic medications had the strongest associations with VTE among medications. This may be valuable for generating hypotheses for the further research. Lercanidipine may be a novel protective medication against VTE.

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“…In addition, it has been shown that BZD receptor agonists significantly increase odds of venous thromboembolism (VTE), with BZD hypnotics having higher odds of VTE. 13 Our study sought to add to the existing literature on immunosuppressive effects and thrombotic complications of BZDs, as it relates to trauma patients. Specifically, we sought to determine if rates of infectious or thrombotic complications among trauma patients were higher in those who tested positive for BZDs on admission.…”

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confidence: 99%

“…Thomassen et al 12 conducted a study that demonstrated that, out of the psychotropic drugs analyzed (antipsychotics, antidepressants, and BZDs), BZDs had the highest odds ratio of developing deep vein thrombosis (DVT). In addition, it has been shown that BZD receptor agonists significantly increase odds of venous thromboembolism (VTE), with BZD hypnotics having higher odds of VTE 13 …”

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confidence: 99%

Benzodiazepines increase the likelihood of both infectious and thrombotic complications

Skicki

Morgan²,

Brown³

et al. 2021

J Trauma Acute Care Surg

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INTRODUCTION:Benzodiazepines (BZDs) modulate peripheral γ-amino-butyric acid type A on macrophages causing immunomodulation. They inhibit proinflammatory cytokines increasing infections. Prior studies have also shown that infections can increase thrombotic complications. We sought to examine this relationship in trauma patients. We hypothesized that the presence of BZDs on admission urine drug screen (UDS) would increase rates of both complications. METHODS:All patients submitted to the Pennsylvania Trauma Outcome Study database from 2003 to 2018 were queried. Those with a positive UDS for BZDs were analyzed. Infectious complications were defined as pneumonia, urinary tract infection, sepsis, wound, and soft tissue infection, and thrombotic complications were defined as presence of pulmonary embolism or deep vein thrombosis. Logistic regressions controlling for demographic and injury covariates assessed the adjusted impact of BZDs on infectious and thrombotic complications. RESULTS:A total of 3,393 patients (2.08%) had infectious complications, and 3,048 (1.87%) had thrombotic complications. Furthermore, 33,260 patients (20.4%) had a positive UDS for BZDs on admission. Univariate analysis showed that those positive for BZDs had higher rates of infectious (3.33% vs. 1.76%, p < 0.001) and thrombotic (2.84% vs. 1.62%, p < 0.001) complications. Multivariate analysis revealed that BZDs significantly increased the odds of infectious and thrombotic complications. Patients who tested positive for BZDs and subsequently developed infection had increased odds (adjusted odds ratio, 1.65; p < 0.001) of developing thrombotic complications. CONCLUSION:Trauma patients with a positive UDS for BZDs had higher odds of both infectious and thrombotic complications. Moreover, odds of thrombotic complications were higher in those with infections.

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Real‐world evidence on the use of benzodiazepine receptor agonists and the risk of venous thromboembolism

Cited by 8 publications

References 39 publications

Analysis of regional differences in the amount of hypnotic and anxiolytic prescriptions in Japan using nationwide claims data

Analysis of regional differences in the amount of hypnotic and anxiolytic prescriptions in Japan using nationwide claims data

A pharmacoepidemiological nested case-control study of risk factors for venous thromboembolism with the focus on diabetes, cancer, socioeconomic group, medications, and comorbidities

Benzodiazepines increase the likelihood of both infectious and thrombotic complications

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