Dataset Information

Benzodiazepines, z-Hypnotics, and Risk of Dementia: Special Considerations of Half-Lives and Concomitant Use.

ABSTRACT: The utilization of benzodiazepines (BZDs) and z-hypnotics has substantially increased with the aging of the population, but the risk of BZDs and z-hypnotics in the development of dementia remains a strong concern. This cohort study aimed to evaluate the risk of BZDs and z-hypnotics for subsequent dementia development with a special consideration of their half-lives and the concomitant use of these medications. People aged 65 years and older who were newly prescribed oral BZDs or z-hypnotics between 2003 and 2012 were identified from Taiwan's National Health Insurance Research Database. All BZDs were categorized as long-acting drugs (≥ 20 h) or short-acting drugs (< 20 h) for further comparisons, and data were collected on a quarterly basis, starting on the first date of drug prescription and ending on the date of death, occurrence of dementia, or end of the follow-up period (December 31, 2012), whichever came first. All dementia events except vascular dementia occurring during the follow-up period were identified. Among 260,502 eligible subjects, short-acting BZDs and z-hypnotics users were at greater risk of dementia than long-acting users [adjusted odds ratio (95% confidence interval) in short-acting BZD users, 1.98 (1.89-2.07); z-hypnotic users, 1.79 (1.68-1.91); and long-acting BZD users, 1.47 (1.37-1.58)]. In addition, subjects concomitantly using 2 or more BZDs or z-hypnotics had a higher risk of dementia than those who used 1 of these drugs (4.79 (3.95-5.81)). The use of BZDs and z-hypnotics was strongly associated with the risk of dementia development, especially the short-acting BZDs, z-hypnotics, and concomitant use of multiple agents. These findings deserve further interventional studies for clarification.

SUBMITTER: Tseng LY

PROVIDER: S-EPMC7007460 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Benzodiazepines, z-Hypnotics, and Risk of Dementia: Special Considerations of Half-Lives and Concomitant Use.

Tseng Li-Yen LY Huang Shih-Tsung ST Peng Li-Ning LN Chen Liang-Kung LK Hsiao Fei-Yuan FY

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20200101 1

The utilization of benzodiazepines (BZDs) and z-hypnotics has substantially increased with the aging of the population, but the risk of BZDs and z-hypnotics in the development of dementia remains a strong concern. This cohort study aimed to evaluate the risk of BZDs and z-hypnotics for subsequent dementia development with a special consideration of their half-lives and the concomitant use of these medications. People aged 65 years and older who were newly prescribed oral BZDs or z-hypnotics betw ...[more]

PMID: 31802436

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Project description:ImportanceUnderstanding the safety profile of medications used in pregnancy is crucial for clinical decision-making. Few studies exist on the associations of exposure to benzodiazepines and benzodiazepine-like hypnotic drugs (z-hypnotics) in pregnancy with pregnancy outcomes.ObjectiveTo determine whether exposure to benzodiazepines or z-hypnotics in pregnancy is associated with greater risk of negative immediate pregnancy outcomes compared with nonexposure.Design, setting, and participantsThis questionnaire-based cohort study used data from the Norwegian Mother, Father and Child cohort study (MoBa), which also includes data from the Medical Birth Registry of Norway. Pregnant women were recruited from all over Norway from 1999 and 2008. The first child was born in October 1999 and the last in July 2009. This analysis included women who completed 3 questionnaires, twice during pregnancy and once 6 months after delivery. Data analyses were conducted from September to November 2019.ExposuresSelf-reported exposure to benzodiazepines or z-hypnotics during pregnancy, characterized in terms of any exposure, timing (ie, early, middle, or late), and duration of exposure.Main outcomes and measuresThe main outcomes were gestational age at delivery, risk of preterm delivery, birth weight, birth weight relative to gestational age and sex, risk of being small for gestational age, head circumference, Apgar score less than 7 at 5 minutes, and risk of neonatal respiratory distress. Continuous outcomes are reported using effect estimates as mean differences, and binary outcomes are reported using risk ratios.ResultsThe MoBa study included 114 234 mother-child dyads. This analysis of MoBa data includes 82 038 singleton pregnancies among 69 434 unique women. Mean (SD) maternal age was 30.2 (4.5) years, and 37 641 pregnancies (45.9%) were in primiparous women. Exposure to benzodiazepines or z-hypnotics was reported in 679 pregnancies (0.8%). After adjusting for all measured baseline and postbaseline confounders, benzodiazepine or z-hypnotic use during pregnancy was associated with lower birth weight (mean difference, -79.3 [95% CI, -126.7 to -31.9] g), lower gestational age at birth (mean difference, -2.1 [95% CI, -3.3 to -0.9] days), and higher risk of preterm birth (risk ratio, 1.41 [95% CI, 1.03 to 1.94]). We found no significant association of exposure to benzodiazepines or z-hypnotics with the child's birth weight relative to gestational age and sex (z score), or any of the other immediate birth outcomes.Conclusions and relevanceThese findings suggest that the magnitude of the association of exposure to benzodiazepines or z-hypnotics with gestational age is not necessarily clinically significant. The absence of an association of exposure to benzodiazepines or z-hypnotics with z score for birth weight relative to gestational age and sex suggests that association of exposure to benzodiazepines or z-hypnotics with birth weight could be explained by earlier delivery rather than impaired intrauterine growth.

Project description:ImportanceEvidence is limited regarding the safety of prenatal benzodiazepine and z-hypnotic exposure and its association with long-term neurodevelopment in childhood.ObjectiveTo quantify the associations of the timing and number of intervals of prenatal exposure to benzodiazepines and/or z-hypnotics with the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood.Design, setting, and participantsThis cohort study used data from the 1999 to 2008 population-based Norwegian Mother, Father and Child Cohort Study, which are linked to the Medical Birth Registry of Norway, Norwegian Patient Registry, and Norwegian Prescription Database. Two populations of participants were created: a full sample and a mental health sample. The full sample included mothers and their live-born singletons, whereas the mental health sample was restricted to offspring of mothers who reported anxiety, depression, or sleeping problems during pregnancy or 6 months before pregnancy. Data were analyzed from September 2021 to February 2022.ExposuresMaternal self-report of benzodiazepine and/or z-hypnotic use during pregnancy was grouped into early pregnancy exposure and middle and/or late pregnancy exposure for analysis of the association with timing of exposure, and number of 4-week intervals of exposure was classified (single [1] vs multiple [≥2]) for analysis of the association with number of exposed intervals.Main outcome and measuresThe outcome was ADHD, defined as time to ADHD diagnosis or filled prescription for ADHD medication. To control for confounding, inverse probability of treatment-weighted Cox proportional hazards regression models were used. Hazard ratios and 95% CIs were estimated. The weights were derived from propensity score modeling of the probability of benzodiazepine and/or z-hypnotic exposure as a function of potential confounders between the exposure and the outcome, including maternal symptoms of depression and anxiety.ResultsThe full sample comprised 82 201 pregnancies, and the mental health sample included 19 585 pregnancies. In total, 681 offspring (0.8%) in the full sample and 468 offspring (2.4%) in the mental health sample were prenatally exposed to benzodiazepines and/or z-hypnotics. After weighting, exposure in early (hazard ratio, 0.74; 95% CI, 0.39-1.94) and middle and/or late (hazard ratio, 0.76; 95% CI, 0.35-1.61) pregnancy was not associated with increased risk of childhood ADHD. There was no evidence of substantial association between the number of exposed intervals during pregnancy and childhood ADHD.Conclusions and relevanceResults of this study suggest that there may be no increased risk of childhood ADHD associated with prenatal exposure to benzodiazepines and/or z-hypnotics, regardless of timing of exposure and number of exposed intervals. However, these findings should be interpreted with caution due to low study power.

Project description:BackgroundConcurrent use of benzodiazepines in opioid users has been linked to a higher risk of an emergency room visit or inpatient admission for opioid overdose and death from drug overdose. Further research is needed to confirm the findings and analyze contributing risk factors for opioid overdoses in a large commercially insured population.ObjectivesTo estimate the risk of opioid overdose associated with opioid users exposed to various combinations of opioid, benzodiazepine, and non-benzodiazepine sedative-hypnotic therapy. To identify other factors that are associated with increased risk for opioid overdose.DesignRetrospective cohort study.PatientsNew start adult users of opioids, defined as naïve to opioids for 6 months, in Kaiser Permanente California regions from January 2013 through September 2017.Main measuresInpatient or emergency department admissions due to opioid-related overdose.Key resultsA total of 2,241,530 patients were included in this study. Patients exposed to opioids, benzodiazepines, and non-benzodiazepine sedative-hypnotics at any point during their follow-up were 60% more likely to overdose than those who were only exposed to opioids (p < 0.0001). Those exposed to opioids and benzodiazepines were 20% more likely to have an opioid-related overdose than those exposed to opioids only (p < 0.0001). Significant risk factors for opioid overdose included exposure to all three medication classes, higher opioid dosage strengths, elderly age (age ≥ 65 years), history of previous overdose, and substance use disorder.ConclusionsResults from this study demonstrate a significant increase in risk of opioid overdose in patients exposed to combinations of sedative-hypnotics with opioids compared to those only taking opioids. Findings from this study provide evidence that opioids should be avoided in combination with benzodiazepines and non-benzodiazepine sedative-hypnotics, used at the lowest dose possible, and used with caution in the elderly, those with previous history of overdose, and those with substance use disorder at baseline.

Dataset Information

Benzodiazepines, z-Hypnotics, and Risk of Dementia: Special Considerations of Half-Lives and Concomitant Use.

Publications

Benzodiazepines, z-Hypnotics, and Risk of Dementia: Special Considerations of Half-Lives and Concomitant Use.

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