Short-acting Benzodiazepine Research Articles

My Benefits From Electroconvulsive Therapy-What a Psychiatrist Learned by Being a Patient.

My Benefits From Electroconvulsive Therapy-What a Psychiatrist Learned by Being a Patient.

Outcome implications of benzodiazepine and opioid co-prescription in kidney transplant recipients.

The outcomes of benzodiazepine and opioid co-prescription are not well-defined in transplant populations. We examined linked national transplant registry and pharmaceutical records to characterize benzodiazepine and opioid use in the years before and after transplant in large US cohort of kidney transplant recipients (2007-2016; N=98620), and associations (adjusted hazard ratio, LCL aHRUCL ) with death and graft failure. Among the cohort, 15.6% filled benzodiazepine prescriptions in the year before transplant, and 14.0% filled benzodiazepine prescriptions in the year after transplant (short-acting, 9.5%; long-acting, 3.3%; both 1.1%). Use of short-acting benzodiazepines in the year before transplant was associated with a 22% increased risk of death in the year after transplant (aHR, 1.08 1.221.38 ), while use of all classes in the year after transplant was associated with increased risk of death from >1 to 5years (aHR: short-acting 1.29 1.391.48 ; long-acting 1.12 1.251.40 ; both 1.46 1.742.07 ). Recipients who used benzodiazepines were also more likely to fill opioid prescriptions. Recipients who filled both classes of benzodiazepine and the highest level of opioids had a 2.9-fold increased risk of death compared to recipients who did not use either. Co-prescription of benzodiazepines and opioids in kidney transplant recipients is associated with increased mortality. Ongoing research is needed to understand mechanisms of risk relationships.

Remimazolam for anaesthesia or sedation.

Anaesthesia and sedation are ubiquitous in contemporary medical practice. Developments in anaesthetic pharmacology are targeted on reducing physiological disturbance whilst maintaining or improving titrateability, recovery profile and patient experience. Remimazolam is a new short-acting benzodiazepine in the final stages of clinical development. Clinical experience with remimazolam comprises volunteer studies and a limited number of clinical investigations. In addition, laboratory investigations explore the implications of its 'soft drug' pharmacology. Remimazolam provides effective procedural sedation with superior success rates and recovery profile when compared to midazolam. Comparisons with propofol are required. Preliminary studies suggest potential for using remimazolam as the hypnotic component of general anaesthesia. Definitive studies are awaited. As a benzodiazepine, remimazolam could be evaluated as an anticonvulsant and for intensive care sedation.

0392 The Effect of Benzodiazepine Use on Non-REM Sleep Instability in Community-Dwelling Older Men

Abstract Introduction Previous studies on the implications of benzodiazepine (BZD), a widely prescribed pharmacotherapeutic treatment method for sleep insomnia, on sleep architecture demonstrated significantly reduced EEG activity in low-frequency bands. In this study, we explore the effect of BZD on NREM sleep instability also known as cyclic alternating pattern (CAP) in community-dwelling older men. Methods CAP was scored in overnight EEG recordings from 30 older men on long-acting BZD (LBZD), 35 older men on short-acting BZD (SBZD), and 50 age-matched men who did not use BZD (NBZD), participating in the Osteoporotic Fractures in Men Sleep Study (MrOS sleep). A high performance automated detection system determined the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). The relationship between CAP parameters and BZD use was determined using the Kruskal-Wallis test by ranks with Bonferroni correction for post-hoc analysis. Results CAP rate was significantly decreased in older men using long-acting BZD (NBZD: 59.6±18.0%, LBZD: 46.9±13.1%, SBZD: 53.0±20.1%) as compared to non-BZD user (p < 0.01). All BZD users demonstrated significantly lower frequencies of A1-phases (NBZD: 19.9±23.0 no./h, LBZD: 6.9±13.3 no./h, SBZD: 4.5±9.9 no./h) as compared to non-BZD users (LBZD: p < 0.01, SBZD: p < 0.001). The A2+A3 index did not show any variations between the three groups. Conclusion Older men using long-acting BZD demonstrate a significantly reduced CAP rate during sleep, particularly less frequent A1-phases, compared to the control group. Moreover, short-acting BZD user show significantly less frequent A1-phases but no difference in CAP rate and A2+A3-phases than older men using no BZD. Hence, BZD usage has a major adverse effect on the occurrence of EEG slow waves. Support The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

Benzodiazepine-Related Cognitive Impairment or Dementia: A Signal Detection Study Using a Case/Non-Case Approach.

ObjectiveThe association between benzodiazepine use and the risk of cognitive impairment or dementia has been controversial. Our study aims to detect this association through a case/non-case method using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2007 and 2016. MethodsCases were adverse event (AE)-pairs with suspected cognitive impairment or dementia. 10 non-cases were matched to each case on age and sex. Exposure was defined as use of benzodiazepines, including long-, intermediate-, and short-acting benzodiazepine. We conducted multivariable logistic regression analyses to estimate reporting odds ratios (ROR) and 95% confidence intervals (CI). ResultsOf the 1,086,584 AE-pairs, 887 cases were suspected AE-pairs of cognitive impairment or dementia, and 775,444 non-cases were selected. Benzodiazepine use was associated with increased AE-pairs of cognitive impairment or dementia when assessed using those with certain, probable, and/or possible in causality assessments (ROR=2.69, 95% CI=1.66–4.38). Higher ROR estimates were shown in female (2.33, 1.48–3.67) and in those with polypharmacy (2.20, 1.35–3.57). Dementia safety profiles were inconsistent across individual benzodiazepine components. ConclusionThese results suggest the potentially increased association between benzodiazepine use and cognitive impairment or dementia in female and those with polypharmacy. Inconsistent safety profiles of benzodiazepine components should be further investigated.

Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis.

Mortality from benzodiazepine/opioid interactions is a growing concern in light of the opioid epidemic. Patients on hemodialysis suffer from a high burden of physical/psychiatric conditions, which are treated with benzodiazepines, and they are three times more likely to be prescribed opioids than the general population. Therefore, we studied mortality risk associated with short- and long-acting benzodiazepines and their interaction with opioids among adults initiating hemodialysis. The cohort of 69,368 adults initiating hemodialysis (January 2013 to December 2014) was assembled by linking US Renal Data System records to Medicare claims. Medicare claims were used to identify dispensed benzodiazepines and opioids. Using adjusted Cox proportional hazards models, we estimated the mortality risk associated with benzodiazepines (time varying) and tested whether the benzodiazepine-related mortality risk differed by opioid codispensing. Within 1 year of hemodialysis initiation, 10,854 (16%) patients were dispensed a short-acting benzodiazepine, and 3262 (5%) patients were dispensed a long-acting benzodiazepine. Among those who were dispensed a benzodiazepine during follow-up, codispensing of opioids and short-acting benzodiazepines occurred among 3819 (26%) patients, and codispensing of opioids and long-acting benzodiazepines occurred among 1238 (8%) patients. Patients with an opioid prescription were more likely to be subsequently dispensed a short-acting benzodiazepine (adjusted hazard ratio, 1.66; 95% confidence interval, 1.59 to 1.74) or a long-acting benzodiazepine (adjusted hazard ratio, 1.11; 95% confidence interval, 1.03 to 1.20). Patients dispensed a short-acting benzodiazepine were at a 1.45-fold (95% confidence interval, 1.35 to 1.56) higher mortality risk compared with those without a short-acting benzodiazepine; among those with opioid codispensing, this risk was 1.90-fold (95% confidence interval, 1.65 to 2.18; Pinteraction<0.001). In contrast, long-acting benzodiazepine dispensing was inversely associated with mortality (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72 to 0.99) compared with no dispensing of long-acting benzodiazepine; there was no differential risk by opioid dispensing (Pinteraction=0.72). Codispensing of opioids and short-acting benzodiazepines is common among patients on dialysis, and it is associated with higher risk of death.

Characteristics of Intravenous Midazolam Sedation with Nitrous Oxide in Pediatric Dental Treatment

Midazolam is a short-acting benzodiazepine that is widely used in pediatric dental sedation. However, its clinical effectiveness as an intravenous sedative agent in children has not been widely documented. A retrospective study was conducted to evaluate the efficacy and safety of intravenous midazolam and nitrous oxide inhalation sedation in pediatric dental treatment.&lt;br/&gt;The subjects were 115 patients (118 cases) who received dental treatment under intravenous midazolam and nitrous oxide inhalation sedation. Demographic factors, general health status, sedation time, midazolam and nitrous oxide dosage, and success rate of sedation were evaluated from electronic medical records.&lt;br/&gt;Behavioral management was the main reason of choosing sedation. Mean duration of sedation was 56.7 minutes for surgical treatment, and 74.4 minutes for restorative treatment. The initial dosage of intravenous midazolam was 0.051 ± 0.019 mg/kg. In 34 cases (28.8%), additional midazolam of 0.036 ± 0.057 mg/kg was delivered during the treatment. The concentration of nitrous oxide was maintained between 40% and 50%. The success rate of sedation was 99% (n = 117). In 1 case, laryngospasm occurred and the patient was reversed with benzodiazepine antagonist, flumazenil.&lt;br/&gt;Intravenous midazolam sedation with nitrous oxide was shown to be clinically effective for the dental treatment in children, if administered by trained personnel and patients are carefully selected in accordance with guidelines.

Evaluation and management of insomnia in clinical practice and in the time of CoViD-19 in Italy: expert consensus and task-force recommendations from five scientific societies

Insomnia symptoms might affect about 60% of the Italian population. Insomnia is a "24 hours syndrome" and a risk factor for medical and mental disorders. It should always be assessed and treated in the clinical practice. Cognitive Behavioral Therapy for Insomnia is the first line treatment but its availability in Italy is scarce. Pharmacological options in Italy are: melatonin 2 mg prolonged release that should be the first choice in subjects ≥55 years old and used until 13 weeks; and for a short term use (≤4 weeks) Z-drugs or short-acting benzodiazepines (in subjects <65 years old) or a sedating antidepressant.

Off-label use of midazolam in older inpatients: analysis of prescribing practices in a French hospital (MIDnight study).

Midazolam is a short-acting benzodiazepine approved for sedation and anesthesia induction. Recent data suggested that midazolam may also be used in off-label indications such as treatment of behavioral and psychological disturbances in older people. Given the scarcity of published data and a lack of evidence in older people in such indications, midazolam raises concern because it may also cause serious-related adverse events. To provide a better understanding of its real-life use in geriatrics, we examined the prescribing practices of midazolam in French older inpatients. Of the 460 patients aged 65years and over hospitalized at the time of the study, 21 had a prescription of midazolam (5%) which was mainly prescribed for anxiolysis (n=12), premedication before painful procedures (n=5), and agitation (n=4). Midazolam was often prescribed "as required," and the median duration of prescription was 6months. This work results in a better knowledge and information about the use of midazolam in older people. These prescribing practices, which are not anecdotal, also plead for age-specific guidelines for the treatment of behavioral and psychological disturbances.

Baseline Functional Connectivity Predicts Connectivity Changes Due to a Small Dose of Midazolam in Older Adults.

In the perioperative context, benzodiazepines are widely used as anxiolytics. They affect cognition in general, but it is unclear whether the effects of a small dose of the short-acting benzodiazepine midazolam can be assessed objectively. To address this scientific question, we conducted a prospective observational study in adults 55-73 years of age. Using both validated psychometric and functional imaging techniques, we determined whether a 2-mg intravenous (IV) dose of midazolam affects cognitive function. We measured the effect of 2 mg IV of midazolam with both the well-established Repeatable Battery for the Assessment of Neuropsychological Status test and resting-state functional magnetic imaging (rs-fMRI) in older adults. Midazolam reduces immediate and delayed memory and has a profound and robust effect on rs-fMRI. Baseline resting-state connectivity predicts memory decline after midazolam administration. Observed effects of midazolam on brain networks were statistically significant even in a small group of volunteers. If validated by other investigators, resting-state brain connectivity may have utility as a measure to predict sensitivity to midazolam in older adults.

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

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.

Risk Factors for Severe Opioid-Related Adverse Events in a National Cohort of Medical Hospitalizations.

Opioids are a leading cause of adverse drug events in the hospital. Guidelines recommend that physicians assess the risks of opioids and discuss them with patients when considering opioid use. There are no studies examining patient- and prescribing-related risk factors for opioid-related adverse drug events (ORADEs) in hospitalized medical patients. To identify independent risk factors for severe ORADEs in hospitalized medical patients. Retrospective cohort study. Medical patients hospitalized at US, non-federal, and acute care facilities, with at least one pharmacy charge for an opioid during hospitalization. We excluded patients with metastatic malignancy, hospice, or palliative care billing codes. We used Cox proportional hazards modeling to identify risk factors for severe ORADEs, defined by a pharmacy charge for naloxone. Candidate risk factors were chosen a priori, based on clinical grounds and prior literature. Among 731,208 hospitalizations (median age 60, 56.5% female), a severe ORADE occurred in 2727 (0.4%). Independent risk factors included patient characteristics (advanced age, female gender), comorbidities (congestive heart failure, opioid abuse/dependence, non-opioid drug abuse/dependence, psychosis, depression, obstructive sleep apnea), organ failures on admission (respiratory failure, shock/hypotension, renal failure, hepatic failure, acidosis, and neurologic failure), medication co-administrations (antipsychotics and short-acting benzodiazepines), and characteristics of the opioid prescriptions themselves (total dose for the day, parenteral route of administration, and receipt of multiple types of opioids in a day). Although a risk prediction model derived from these factors performed well on stratified k-fold cross-validation (average c-statistics 0.68-0.71), the low incidence of the outcome limited the positive predictive value of the risk score. In this national cohort of medical patients, we identified several risk factors for ORADEs that can be used to inform physician decision-making, conversations with patients about risk, and development and targeting of harm reduction strategies for at-risk populations.

Efficacy of oral midazolam for minimal and moderate sedation in pediatric patients: A systematic review.

One of the most widely used options for minimal/moderate sedation in pediatric patients is oral midazolam, as it presents an alternative to less well‐accepted routes of administration (eg, intravenous or intranasal) of this well‐known efficacious and well‐tolerated short‐acting benzodiazepine. A systematic review of the literature was conducted in order to identify clinical studies evaluating the effectiveness of oral midazolam for sedation in pediatric patients in the context of premedication before anesthesia or during diagnostic/treatment procedures. The percentage of responders (response rate) after single administration of oral midazolam was evaluated and compared versus placebo in a subset of placebo‐controlled studies. The range of oral midazolam doses providing effective sedation in the different pediatric age subsets was analyzed in order to assess optimum dosing strategies. A total of 25 pediatric clinical studies, utilizing a variety of measures of sedation effectiveness, were selected. These studies included a total of 1472 patients (aged 4 months‐18 years) treated with midazolam (0.25‐1.5 mg/kg) and 138 patients treated with placebo. The response rates [95% confidence interval] with oral midazolam ranged from 36.7% [21.6%, 54.9%] to 97.8% [86.1%, 99.7%], while with placebo response rates ranged from 4.0% [0.6%, 23.5%] to 41.0% [29.4%, 53.6%]. When considering the 4 placebo‐controlled studies, the odds ratios [95% confidence interval] for the comparison of midazolam vs. placebo ranged from 13.4 [5.0, 36.0] to 25.9 [6.7, 100.6]. The analysis of subgroups by context of sedation showed response rates [95% confidence interval] with oral midazolam ranging from 36.7% [21.6%, 54.9%] to 97.0% [94.8%, 98.3%] for anesthetic premedication and from 56.1% [43.1%, 68.4] to 97.8% [86.1%, 99.7%] for medical procedures. The efficacy of midazolam for pediatric minimal/moderate sedation from a dose of 0.25 mg/kg and above was demonstrated. The probability of occurrence of adverse events and over‐sedation increases with increasing doses.

Benzodiazepine use and brain amyloid load in nondemented older individuals: a florbetapir PET study in the Multidomain Alzheimer Preventive Trial cohort

It remains unclear whether benzodiazepines (BZDs) constitute a risk factor for Alzheimer's disease (AD). In this study, we investigated associations between chronic use of BZDs and brain amyloid load, a hallmark of AD, in 268 nondemented older individuals. F18-florbetapir positron emission tomography scans were performed to assess amyloid load as measured by standardized uptake value ratios, which were compared between chronic BZD users and nonusers using adjusted multiple linear regressions. Short- versus long-acting BZDs were also considered in the analyses. Standardized uptake value ratios were significantly lower in BZD users (n = 47) than in nonusers (n = 221), independent of multiple adjustments. The effect was stronger for short-acting BZDs than for long-acting BZDs. This is the first large clinical study showing a reduced brain amyloid load in chronic BZD users, especially with short-acting BZDs. Our results do not support the view of BZD use as a risk factor for AD and instead support the involvement of pharmacological mechanisms related to neuronal hyperactivity, neuroinflammation, and sleep quality as potential targets for blocking amyloid accumulation.

Medication management issues identified during home medication reviews for ambulatory community pharmacy patients.

The health risks associated with poor medication practices in the home suggest that patients would benefit from home-based medication reviews that could detect and resolve these issues. However, remuneration for home visits often excludes ambulatory, nonhomebound patients. A subset of these patients have issues that cannot be adequately identified and resolved during the course of a typical pharmacy-based medication review. This study aims to characterize the prevalence and nature of "hidden in the home" medication management issues in nonhomebound patients. Pharmacists facilitated subject enrollment among patients at 6 community pharmacies in Toronto over a 15-month period, from January 2016 to March 2017. Patients taking 5 or more chronic medications who were ambulatory (able to visit the pharmacy) and scored 3 points or higher on a prescreening questionnaire were invited to participate. Visits included a standard medication review, the identification of drug therapy problems and an assessment of the patient's medication and organization/storage practices, followed by a medication cabinet cleanup. One hundred patients were recruited, with a mean age of 76.9 years and taking on average 10 chronic medications. Pharmacists identified a total of 275 drug therapy problems (2.75 per patient). The most common issues reported additional therapy required (23.6%), nonadherence (23.3%) and adverse drug reactions (17.8%). For those patients 65 years or older (87%), 32% were found to be using at least 1 medication on the Beers Criteria list, while 6% were using 3 or more. Sulfonylureas, non-steroidal anti-inflammatory drugs and short-acting benzodiazepines were the most commonly implicated drugs. Medications were removed from the homes of 67% of the patients, with expiry of medication being the most common reason for removal (54.2%). The mean duration of a home visit was 49.5 minutes. Pharmacist-directed home medication reviews offer an effective mechanism to address the pharmacotherapy issues of patients taking multiple medications. These findings highlight the frequency of medication management issues in this group and suggest that home medication reviews could serve to minimize inappropriate use of medication and maximize health care cost savings in this unique patient population. Can Pharm J (Ott) 2019;152:xx-xx.

Association Between Incident Exposure to Benzodiazepines in Early Pregnancy and Risk of Spontaneous Abortion

Benzodiazepine use in early pregnancy is associated with spontaneous abortion (SA). However, to date, the association between specific benzodiazepine agent exposure and the risk of SA has not been examined. To quantify the risk of SA associated with gestational benzodiazepine incident use by drug class, duration of action, and specific benzodiazepine agent. This nested case-control study within the Quebec Pregnancy Cohort, Montreal, Quebec, Canada, includes all pregnancies covered by the Quebec Prescription Drug Insurance Plan from January 1, 1998, through December 31, 2015. Each case was randomly matched with up to 5 controls. Statistical analysis was performed from January 1, 1998, through December 31, 2015. Benzodiazepine exposure was defined as 1 or more filled prescriptions between the first day of the last menstrual period and the index date (the calendar date of the SA diagnosis). Benzodiazepine exposure was categorized by overall use, long- or short-acting benzodiazepine, and specific benzodiazepine agents. Spontaneous abortion defined as a pregnancy loss between the beginning of the sixth week of gestation and the 19th completed week of gestation. Conditional logistic regression models were used to calculate odds ratios (OR) and 95% CIs. Of the 442 066 pregnancies included in the Quebec Pregnancy Cohort, 27 149 (6.1%) ended with SA, with a mean (SD) maternal age of 24.2 (6.5) years. Among pregnancies ending with SA, 375 (1.4%) were among women exposed to benzodiazepines in early pregnancy compared with 788 (0.6%) of the 134 305 matched control pregnancies (crude OR, 2.39; 95% CI, 2.10-2.73). Adjusting for potential confounders, including maternal mood and anxiety disorders before pregnancy, and compared with nonuse, benzodiazepine exposure in early pregnancy was associated with an increased risk of SA (adjusted OR, 1.85; 95% CI, 1.61-2.12). The risk was similar among pregnancies exposed to short-acting (284 exposed cases; adjusted OR, 1.81; 95% CI, 1.55-2.12) and long-acting (98 exposed cases; adjusted OR, 1.73; 95% CI, 1.31-2.28) benzodiazepines during early pregnancy. All benzodiazepine agents were independently associated with an increased risk of SA (range of adjusted ORs, 1.13-3.43). An increased risk of SA was observed among early pregnancies with incident exposure to short- and long-acting benzodiazepines and all specific benzodiazepine agents during early pregnancy. Insomnia, anxiety, and mood disorders are prevalent during pregnancy; clinicians should carefully evaluate the risk-benefit ratio of prescribing benzodiazepines in early pregnancy since alternative nonpharmacologic treatments exist.

Signal detection of benzodiazepine use and risk of dementia: sequence symmetry analysis using South Korean national healthcare database.

Background Benzodiazepine use can potentially cause confusion and delays in mental processes. These well-known side effects appear to be linked to an increased risk of being diagnosed with dementia. Objective To evaluate the possibility of an association between benzodiazepine and dementia. Setting Korean healthcare database from 2002 to 2013. Methods Sequence symmetry analysis was conducted to investigate whether benzodiazepine use increases the risk of dementia or not. We defined exposure as new benzodiazepine users and outcome as new diagnosis of dementia (ICD-10: F00-03, G30, and G318). Benzodiazepines were categorized into two groups (long-acting and short-acting) based on the duration of action. Antidepressants, opioid analgesic, and statin were used as active comparators to rule out any possible non-causal interpretations of our results. The time-trend adjusted sequence ratio (ASR) with 95% confidence intervals (CI) was measured to identify possible associations. Main outcome measure Adjusted sequence ratio. Results Benzodiazepine users were shown to be associated with dementia [benzodiazepine: 4212 pairs, ASR = 2.27 (95% CI 2.11-2.44)]. In addition, long-acting benzodiazepines had ahigher ASR than that of short-acting benzodiazepines [long-acting: 3972 pairs, ASR = 2.22 (95% CI 2.06-2.39] and [short-acting: 5213 pairs, ASR = 1.88 (95% CI 1.77-2.00)]. However, our SSA found no duration-response relationship. Conclusion Our signal detection suggests that there is a possible association between benzodiazepines and dementia. Additionally, it proposes that persons receiving long-acting benzodiazepines are at a higher risk of developing dementia than those receiving short-acting benzodiazepines. Further studies are recommended to confirm whether this epidemiological association is a causal effect or not.

Association between Development of Dementia and Use of Benzodiazepines: A Systematic Review and Meta-Analysis.

The use of benzodiazepines and the development of dementia is controversial, with studies indicating that benzodiazepines could be either a protective factor or a risk factor for dementia, or no association may exist between the two. Our objective was to identify whether such an association exists. Systematic review and meta-analysis of 12 prospective and retrospective cohort studies and case-control studies. A total of 981,133 (in the systematic review) and 980,860 (in the meta-analysis) adults or elderly individuals. A search of the PubMed, LILACS, and Cochrane Central Register of Controlled Trials databases, as well as a manual search of the reference lists of the included publications and reviews, was performed. We included studies that reported the incidence of dementia and in ever users of benzodiazepines. Data were analyzed by using a random effects model in R software. Quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty ratings system. The results of the main meta-analysis suggest that benzodiazepines can be a risk factor for developing dementia (odds ratio 1.38, 95% confidence interval 1.07-1.77; I2 = 98%; 95% prediction interval 0.58-3.25; very low certainty). Our results suggest an association between the use of benzodiazepines and the development of dementia. However, the current evidence lacks the power to infer differences between the effects of Alzheimer's disease and vascular dementias, long-acting and short-acting benzodiazepines, and various exposure loads (duration and dose). Future long-term prospective cohort studies are necessary, with adequate adjustments for confounding variables, strategies to minimize reverse causality, reporting of subgroups aimed at greater homogeneity of findings, adequate statistical power to identify high-magnitude effects, and defined daily dose analyses for dose-response gradient.

Are short-acting or long-acting benzodiazepines more effective in decreasing the severity of alcohol withdrawal symptoms?

Are short-acting or long-acting benzodiazepines more effective in decreasing the severity of alcohol withdrawal symptoms?

A Systematic Review and Meta-Analysis of the Risk of Dementia Associated with Benzodiazepine Use, After Controlling for Protopathic Bias

Benzodiazepine use is highly prevalent in elderly and late middle-aged populations and may be associated with an increased risk of dementia. Observational studies have suggested that benzodiazepine use may increase the risk of dementia, however there have been significant concerns regarding protopathic bias in these studies, precluding conclusive findings. The aim of our study was to investigate the risk of dementia associated with the use of benzodiazepines in elderly patients, after controlling for protopathic bias. We identified observational studies with more than 50cases, adequate assessment of benzodiazepine exposure, and reliable dementia diagnosis ascertainment, from the MEDLINE, PubMed, EMBASE, CINAHL, LILACS and CENTRAL electronic databases through to 5 June 2018, with no language limits. The association of any current or former use of short- or long-acting benzodiazepines with incident dementia was analysed. A subgroup analysis was performed by the introduction of lag time to assess the effect of protopathic bias. We also performed analyses considering the effect of higher benzodiazepine cumulative doses and adjustment for psychiatric covariates. Study quality was investigated using the Newcastle-Ottawa Scale. We identified 15 studies reported in 14 articles, involving 159,090 cases. Ever use of benzodiazepines was associated with a significantly increased risk of dementia [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.21-1.59]. Those studies that implemented the longest lag times of ≥ 5years, and hence most likely to overcome protopathic bias, found a risk estimate that was marginally attenuated, but still significant (OR 1.30, 95% CI 1.14-1.48). Long-acting benzodiazepines were associated with a marginally higher magnitude risk (OR 1.21, 95% CI 0.99-1.49) than short-acting benzodiazepines (OR 1.13, 95% CI 1.02-1.26), although the former failed to reach statistical significance (p = 0.059). Our findings indicate that the association between benzodiazepine use and dementia incidence is not purely an artefact due to protopathic bias. Reduction of inappropriate benzodiazepine prescription is likely to attenuate dementia risk.