Use of sedative-hypnotics and the risk of Alzheimer's dementia: A retrospective cohort study.
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ABSTRACT:
SUBMITTER: Lee J
PROVIDER: S-EPMC6152975 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:[This corrects the article DOI: 10.1371/journal.pone.0204413.].
| S-EPMC6191145 | biostudies-literature
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.
| S-EPMC7080944 | biostudies-literature
Project description:BackgroundSleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality.MethodsWe conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations.ResultsCompared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78-1.85) and mixed users (HR = 1.44; 95% CI = 1.42-1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71-0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk.ConclusionsThe effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality.
| S-EPMC4692546 | biostudies-literature
Project description:The objective of this study was to test the hypothesis that use of zolpidem, eszopiclone, and zaleplon would be associated with increased risk of traumatic brain injury (TBI) and hip fracture.We conducted a case-crossover study on a 5% random sample of Medicare beneficiaries age 65 y or older hospitalized with either TBI (n = 15,031) or hip fracture (n = 37,833) during 2007-2009. Use of zolpidem, eszopiclone, or zaleplon during the 30-day period prior to injury hospitalization was compared to use during four control periods at 3, 6, 9, and 12 mo prior to injury. The primary outcome was hospitalization for TBI or hip fracture.Zolpidem use during the month prior to injury was associated with increased risk of TBI (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.56, 2.25); however, eszopiclone use during the same period was not associated with increased risk (OR 0.67; 95% CI 0.40, 1.13). Zolpidem use during the month prior to injury was associated with increased risk of hip fracture (OR 1.59; 95% CI 1.41, 1.79); however, eszopiclone use during the same period was not associated with increased risk (OR 1.12; 95% CI 0.83, 1.50). Analysis of zaleplon use in the month prior to injury was limited by low drug utilization but was not associated with increased risk of TBI (OR 0.85; 95% CI 0.21, 3.34) or hip fracture (OR 0.92; 95% CI 0.40, 2.13) in this study.For the treatment of insomnia in older adults, eszopiclone may present a safer alternative to zolpidem, in terms of fall-related injuries.
| S-EPMC4835298 | biostudies-other
Project description:BackgroundPrevious findings regarding the association between benzodiazepine exposure and dementia have conflicted, though many have not accounted for anticholinergic exposure. The goal of this study was to evaluate the association of benzodiazepine exposure with the risk of developing dementia, accounting for the anticholinergic burden.MethodsUsing a retrospective cohort design, we identified veterans 65 or older without dementia during a 10-year baseline period and then followed participants for 5 years to evaluate the risk of dementia diagnosis. The primary exposure was cumulative benzodiazepine exposure. Cox proportional hazards survival model was used to examine the association between benzodiazepine exposure and dementia, adjusting for anticholinergic burden and other demographic and clinical characteristics associated with increased dementia risk.ResultsOf the 528 006 veterans in the study cohort, 28.5% had at least one fill for a benzodiazepine. Overall, 7.9% developed a diagnosis of dementia during the observation period. Compared to veterans with no exposure to benzodiazepines, the adjusted hazard ratios for dementia risk were 1.06 (95% confidence interval [CI] 1.02-1.10) for low benzodiazepine exposure, 1.05 (95% CI 1.01-1.09) for medium benzodiazepine exposure, and 1.05 (95% CI 1.02-1.09) for high benzodiazepine exposure.ConclusionsCumulative benzodiazepine exposure was minimally associated with increased dementia risk when compared with nonuse but did not increase in a dose-dependent fashion with higher exposure. Veterans with low benzodiazepine exposure had essentially the equivalent risk of developing dementia as veterans with high exposure. While benzodiazepines are associated with many side effects for older adults, higher cumulative use does not appear to increase dementia risk.
| S-EPMC9071459 | biostudies-literature
Project description:BackgroundSedative hypnotics form an important part of managing insomnia and are recommended for short-term use. It is standard practice for clinicians to inform the patient to use medications only 'when required', but the use of these medications is often chronic. Little is known about the impact of standard labelling/instructions on promoting appropriate medication use for managing insomnia.ObjectiveTo explore patient medication-taking beliefs, experiences and behavioural practices relating to the use of pharmacological/complementary sleep aids for insomnia.Setting and participantsSpecialist sleep/psychology clinics and the general community in Sydney, Australia.MethodSemi-structured interviews were conducted with 51 people with insomnia using a schedule of questions to gauge their experiences, beliefs and current practices relating to insomnia medication use. Interviews were audio-recorded, transcribed verbatim and subjected to Framework Analysis to identify emergent themes.ResultsParticipants held distinctive views about the safety and efficacy of complementary and pharmacological agents but do not intuitively turn to medications to resolve their sleep complaint. Medication use was affirmed through tangible medication-taking cues due to the ambivalence in current instructions and labelling. Practices such as dosage modification, medication substitution and delaying medication use might be important drivers for psychological dependence.ConclusionCurrent labelling and instructions do not necessarily promote the quality use of sedative hypnotics due to the variability in patient interpretations. Clarifying the timing, quantity and frequency of medication administration as well as insomnia symptom recognition would play a significant role in optimizing the role of pharmacotherapy in the management of insomnia.
| S-EPMC5042066 | biostudies-literature
Project description:BackgroundBenzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.Methods and findingsThe retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.ConclusionsIn US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.
| S-EPMC8321368 | biostudies-literature
Project description:BackgroundSedative-hypnotics are frequently prescribed for insomnia in hospital but are associated with preventable harms.Objective, design, and participantsWe aimed to examine whether a sedative-hypnotic reduction quality improvement bundle decreases the rate of sedative-hypnotic use among hospitalized patients, who were previously naïve to sedative-hypnotics. This interrupted time series study occurred between May 2016 and January 2019. Control data for 1 year prior to implementation and intervention data for at least 16 months were collected. The study occurred on 7 inpatient wards (general medicine, cardiology, nephrology, general surgery, and cardiovascular surgery wards) across 5 teaching hospitals in Toronto, Canada.InterventionParticipating wards implemented a sedative-hypnotic reduction bundle (i.e., order set changes, audit-feedback, pharmacist-enabled medication reviews, sleep hygiene, daily sleep huddles, and staff/patient/family education) aimed to reduce in-hospital sedative-hypnotic initiation for insomnia in patients who were previously naïve to sedative-hypnotics. Each inpatient ward adapted the bundle prior to sustaining the intervention for a minimum of 16 months.Main measuresThe primary outcome measure was the proportion of sedative-hypnotic-naïve inpatients newly prescribed a sedative-hypnotic for sleep in hospital. Secondary measures include prescribing rates of other sedating medications, fall rates, length of stay, and mortality.Key resultsWe included 8,970 patient discharges in the control period and 10,120 in the intervention period. Adjusted sedative-hypnotic prescriptions among naïve patients decreased from 15.48% (95% CI: 6.09-19.42) to 9.08% (p<0.001) (adjusted OR 0.814; 95% CI: 0.667-0.993, p=0.042). Unchanged secondary outcomes included mortality (adjusted OR 1.089; 95% CI: 0.786-1.508, p=0.608), falls (adjusted rate ratio 0.819; 95% CI: 0.625-1.073, p=0.148), or other sedating drug prescriptions (adjusted OR 1.046; 95% CI: 0.873-1.252, p=0.627).ConclusionsA sedative-hypnotic reduction quality improvement bundle implemented across 5 hospitals was associated with a sustained reduction in sedative-hypnotic prescriptions.
| S-EPMC9360352 | biostudies-literature
Project description:Sedative–hypnotic misuse is associated with psychiatric diseases and overdose deaths. It remains uncertain whether types of anesthesia affect the occurrence of new postoperative uses of sedative–hypnotics (NPUSH). We used reimbursement claims data of Taiwan’s National Health Insurance and conducted propensity score matching to compare the risk of NPUSH between general and neuraxial anesthesia among surgical patients who had no prescription of oral sedative–hypnotics or diagnosis of sleep disorders within the 12 months before surgery. The primary outcome was NPUSH within 180 days after surgery. Multivariable logistic regression models were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 92,222 patients were evaluated after matching. Among them, 15,016 (16.3%) had NPUSH, and 2183 (4.7%) were made a concomitant diagnosis of sleep disorders. General anesthesia was significantly associated both with NPUSH (aOR: 1.17, 95% CI: 1.13–1.22, p < 0.0001) and NPUSH with sleep disorders (aOR: 1.11, 95% CI: 1.02–1.21, p = 0.0212) compared with neuraxial anesthesia. General anesthesia was also linked to NPUSH that occurred 90–180 days after surgery (aOR: 1.12, 95% CI: 1.06–1.19, p = 0.0002). Other risk factors for NPUSH were older age, female, lower insurance premium, orthopedic surgery, specific coexisting diseases (e.g., anxiety disorder), concurrent medications (e.g., systemic steroids), postoperative complications, perioperative blood transfusions, and admission to an intensive care unit. Patients undergoing general anesthesia had an increased risk of NPUSH compared with neuraxial anesthesia. This finding may provide an implication in risk stratification and prevention for sedative–hypnotic dependence after surgery.
| S-EPMC9224548 | biostudies-literature
Project description:This study investigated the association of statin use with sepsis risk in patients with dementia. This retrospective cohort study was conducted in Taiwan by using data from the National Health Insurance Research Database. We identified and enrolled 308 patients with newly diagnosed dementia who used statin after dementia diagnosis. These patients were individually propensity score matched (1:1) according to age, sex, hypertension, hyperlipidemia, diabetes, cerebrovascular disease, renal disease, liver disease, asthma, malignancy, parkinsonism, and dementia drugs used (donepezil, rivastigmine, galantamine, and memantine) with 251 controls (statin non-users). A Cox proportional hazard model was used to estimate the adjusted hazard ratio for sepsis in statin users and non-users. After adjustment for other confounding factors, the incidence of sepsis in statin users was 1.42-fold higher than that in non-users (95% confidence interval = 0.81-2.5). In conclusion, our analysis showed no positive association of sepsis with statin use in patients with dementia.
| S-EPMC6539698 | biostudies-literature