Use of benzodiazepine and risk of cancer: A meta-analysis of observational studies

Kim, Hong Bae; Myung, Seung‐Kwon; Park, Yon Chul; Park, Byoungjin

doi:10.1002/ijc.30443

Cited by 34 publications

(17 citation statements)

References 56 publications

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“…Currently, there is still a lack of conclusive experimental data, but alarm signals for cancer risk have been raised by researchers for hypnotic drugs based on observational study findings [ 26 , 27 , 28 , 33 ]. A previous meta-analysis of 22 observational studies (18 case-control and 4 cohort studies) concluded there is an overall estimate of 19% increased cancer risk, with a significant dose–response trend, among benzodiazepines users over non-users [ 47 ]. A meta-analysis performed by Kim et al (2017) included 6 observational epidemiological studies (3 case-control and 3 cohort studies) [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies

Peng

Yang

et al. 2020

Medicina

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Background and objectives: The association between hypnotic drugs and risk of cancer remains controversial. Therefore, we performed a meta-analysis to investigate this association. Materials and Methods: Pubmed and Embase were searched systematically to identify publications up to April 2020. The Newcastle-Ottawa scale for observational studies was used to assess the quality of studies. All included studies were evaluated by two reviewers independently; any discrepancies were resolved through discussion. Results: Twenty-eight studies including 22 case-control studies and 6 cohort studies with 340,614 hypnotics users and 1,828,057 non-users were included in the final analyses. Hypnotics (benzodiazepines and Z-drugs) use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.17; 95% confidence interval 1.09–1.26) in a random-effects meta-analysis of all studies. Subgroup meta-analysis by anxiolytics/sedatives effect (anxiolytics benzodiazepines vs. sedatives group (include sedatives benzodiazepines and Z-drugs)) revealed that a significant association in sedatives group (pooled OR/RR 1.26, 95% CI, 1.10–1.45), whereas no significant relationship was observed in anxiolytics benzodiazepines (pooled OR/RR 1.09, 95% CI, 0.95–1.26). Moreover, a significant dose–response relationship was observed between the use of hypnotics and the risk of cancer. Conclusions: This meta-analysis revealed association between use of hypnotics drugs and risk of cancer. However, the use of lower dose hypnotics and shorter duration exposed to hypnotics seemed to be not associated with an increased risk of cancer. Moreover, the use of anxiolytics effect benzodiazepines seemed to be lower risk than sedatives benzodiazepines. A high heterogeneity was observed among identified studies, and results were inconsistent in some subgroups. Randomized control trials are needed to confirm the findings in the future.

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Section: Discussionmentioning

confidence: 99%

Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies

Peng

Yang

et al. 2020

Medicina

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“…Despite the lack of conclusive experimental data, alarm signals for cancer risk have been raised by researchers for benzodiazepines and the Z-drugs based on observational study findings [ 136 – 139 ]. In attempts to get a clear answer to this quandary, Kim et al published a 2016 meta-analysis of 22 observational studies (18 case–control and 4 cohort) which concluded an overall estimate of 19% increased cancer risk, with a significant dose-response trend, among benzodiazepine users over non-users [ 140 ]. There does exist a fine degree of granularity when it comes to the determination of cancer risk from benzodiazepines/Z-drugs as certain types of cancer (i.e., esophageal, brain, pancreatic) and certain agents (lorazepam, clonazepam, zopiclone) carry greater statistical weight, driving the overall association [ 137 , 140 ].…”

Section: Cancermentioning

confidence: 99%

“…In attempts to get a clear answer to this quandary, Kim et al published a 2016 meta-analysis of 22 observational studies (18 case–control and 4 cohort) which concluded an overall estimate of 19% increased cancer risk, with a significant dose-response trend, among benzodiazepine users over non-users [ 140 ]. There does exist a fine degree of granularity when it comes to the determination of cancer risk from benzodiazepines/Z-drugs as certain types of cancer (i.e., esophageal, brain, pancreatic) and certain agents (lorazepam, clonazepam, zopiclone) carry greater statistical weight, driving the overall association [ 137 , 140 ]. Given that most of the studies included in the meta-analysis are retrospective, the authors address the limitations fairly by reminding us of confounding by indication (cancer patients more likely to use anxiolytic medication) and unmeasured confounding (alcohol and smoking) [ 140 ].…”

Section: Cancermentioning

confidence: 99%

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

2017

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Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of sedative-hypnotic medication, especially of the benzodiazepine and related Z-drug variety. However, the last few years have seen increasing reports in the literature raising the issue of benzodiazepine and Z-drug exposure in the development of other serious medical issues including dementia, infections, respiratory disease exacerbation, pancreatitis, and cancer. This article provides an overview and interpretation on the current state of evidence regarding each of these associations and proposes what gaps in the evidence for drug-exposure–harm associations need to be addressed in the future for the purpose of evaluating causality of harm as it relates to these drugs.

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“…Patients may become dependent on BZDs to avoid withdrawal symptoms 1–3. Studies have shown several adverse consequences related to the long-term use of BZD, including fracture,4 5 cancer6 and car accidents7 in any age group.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with long-term prescription of benzodiazepine: a retrospective cohort study using a health insurance database in Japan

et al. 2019

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ObjectivesCurrent clinical guidelines discourage long-term prescription of benzodiazepines and Z-drugs (BZD); however, the practice continues to exist. The aim of this study was to investigate the proportion of long-term BZD prescriptions and its risk factors.DesignRetrospective cohort study using a health insurance database.SettingJapan.ParticipantsA total of 86 909 patients were identified as outpatients aged 18 to 65 years who started BZD between 1 October 2012 and 1 April 2015. After excluding patients who underwent surgery on the day of first BZD prescription (n=762) and patients without 8 months follow-up (n=12 103), 74 044 outpatients were analysed.Main outcome measuresWe investigated the proportion of long-term prescriptions for ≥8 months among new BZD users. We assessed patient demographics, diagnoses, characteristics of the initial BZD prescription and prescribers as potential predictors of the long-term BZD prescription. Multivariable logistic regression was performed to assess the association between long-term prescription and potential predictors.ResultsOf the new BZD users, 6687 (9.0%) were consecutively prescribed BZD for ≥8 months. The long-term prescription was significantly associated with mood and neurotic disorder, cancer, prescription by psychiatrists, multiple prescriptions, hypnotics and medium half-life BZD in the initial prescription.ConclusionDespite the recent clinical guidelines, 9% of new BZD users were given prescriptions for more than 8 months. Physicians should be aware of risk factors when prescribing BZDs for the first time.

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Use of benzodiazepine and risk of cancer: A meta-analysis of observational studies

Cited by 34 publications

References 56 publications

Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies

Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

Factors associated with long-term prescription of benzodiazepine: a retrospective cohort study using a health insurance database in Japan

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