Gender and use of hypnotics or sedatives in old age: a nationwide register-based study

Objective To investigate whether gender is associated with use of hypnotics or sedatives and with different types of hypnotics or sedatives in older people after adjustment for age, socioeconomic status (i.e., education) and co-morbidity (i.e., number of other drugs). Setting Sweden Method We conducted a register-based analysis of data on gender, age, dispensed drugs, and education from people aged 75-89 years registered in the Swedish Prescribed Drug Register between July and October 2005 (n = 645,429). Main outcome measure The hypnotic or sedative drug classes were benzodiazepines, benzodiazepine related drugs (i.e., Z-drugs) and other types of hypnotics or sedatives. The individual hypnotics or sedatives were nitrazepam, flunitrazepam, triazolam, zopiclone, zolpidem, clomethiazole and propiomazine. Results In the total study population, 27.1% of the women and 18.1% of the men were dispensed at least one hypnotic or sedative drug. The logistic regression analyses of those who used hypnotics or sedatives (n = 151,700) revealed that women were more likely than men to use benzodiazepines (adjusted OR = 1.11; 95% CI 1.07?C1.14) and benzodiazepine related drugs (adjusted OR = 1.14; 95% CI 1.12?C1.17), whereas men were more likely to use other types of hypnotics or sedatives (adjusted OR = 0.69; 95% CI 0.67?C0.71). Among the individual hypnotics or sedatives, the strongest associations with gender was found for nitrazepam (adjusted OR = 1.19; 95% CI 1.14?C1.25 for women compared with men), zolpidem (adjusted OR = 1.18; 95% CI 1.16?C1.21), clomethiazole (adjusted OR = 0.48; 95% CI 0.46?C0.51) and propiomazine (adjusted OR = 0.77; 95% CI 0.75?C0.79). Conclusion Use of hypnotics or sedatives in old age seems to be related to female gender. Also, among elderly users of hypnotics or sedatives, women appear to be more likely to use benzodiazepines and benzodiazepine related drugs than men. The explanation to these gender differences merits further investigation.     

Benzodiazepine use in an elderly community-dwelling population. Characteristics of users and factors associated with subsequent use

OBJECTIVES: The objective of this study was to describe determinants of current and subsequent benzodiazepine use in an elderly population, the Paquid cohort. METHODS: The study was conducted on a cohort of 2,792 community-dwelling subjects 65 years of age or more living in the Gironde department, southwestern France. Benzodiazepine use and its correlates were studied with data collected at inclusion in the cohort. Longitudinal analysis over a 5-year period of follow-up was done to identify baseline predictors of subsequent use. RESULTS: At baseline, prevalence rate of benzodiazepine use was 31.9%. It was associated with female gender [odds ratio (OR) = 2.0; 95% confidence interval (CI): 1.66, 2.46], previous psychiatric disease (OR = 2.87; 95% CI: 2.31, 3.56), concomitant antidepressant use (OR = 2.45; 95% CI: 1.59, 3.78), depressive symptomatology (OR = 1.70; 95% CI: 1.28, 2.26), multiple drug use (OR = 1.82; 95% CI: 1.50, 2.21), multiple chronic diseases (OR = 1.37; 95% CI: 1.12, 1.67) and poor self-perceived health (OR = 1.63; 95% CI: 1.33, 2.0). For the 1926 benzodiazepine non-users at inclusion and followed during 5 years, incidence rate of subsequent use was 5.37 per 100 person-years (95% CI: 4.76, 5.98). In multivariate Cox proportional hazards regression analysis, previous psychiatric diseases, poor self-perceived life satisfaction and polymorbidity were significantly associated with subsequent benzodiazepine use. CONCLUSIONS: Elderly people are heavy users of benzodiazepines. Independently from mental health status, those in poor health were most at risk of benzodiazepine use.     

High enhancer,downer, withdrawal helper: Multifunctional nonmedical benzodiazepine use among young adult opioid users in New York City

BackgroundBenzodiazepines are a widely prescribed psychoactive drug; in the U.S., both medical and nonmedical use of benzodiazepines has increased markedly in the past 15 years. Long-term use can lead to tolerance and dependence, and abrupt withdrawal can cause seizures or other life-threatening symptoms. Benzodiazepines are often used nonmedically in conjunction with other drugs, and with opioids in particular—a combination that can increase the risk for fatal and non-fatal overdose. This mixed-methods study examines nonmedical use of benzodiazepines among young adults in New York City and its relationship with opioid use.MethodsFor qualitative analysis, 46 90-minute semi-structured interviews were conducted with young adult opioid users (ages 18–32). Interviews were transcribed and coded for key themes. For quantitative analysis, 464 young adult opioid users (ages 18–29) were recruited using Respondent-Driven Sampling and completed structured interviews. Benzodiazepine use was assessed via a self-report questionnaire that included measures related to nonmedical benzodiazepine and opioid use.ResultsParticipants reported using benzodiazepines nonmedically for a wide variety of reasons, including: to increase the high of other drugs; to lessen withdrawal symptoms; and to come down from other drugs. Benzodiazepines were described as readily available and cheap. There was a high prevalence (93%) of nonmedical benzodiazepine use among nonmedical opioid users, with 57% reporting regular nonmedical use. In bivariate analyses, drug-related risk behaviours such as polysubstance use, drug binging, heroin injection and overdose were strongly associated with regular nonmedical benzodiazepine use. In multivariate analysis, growing up in a middle-income household (earning between $51,000 and $100,000 annually), lifetime overdose experience, having ever used cocaine regularly, having ever been prescribed benzodiazepines, recent drug binging, and encouraging fellow drug users to use benzodiazepines to cope with opioid withdrawal were consistently strong predictors of regular nonmedical benzodiazepine use.ConclusionNonmedical benzodiazepine use may be common among nonmedical opioid users due to its drug-related multi-functionality. Harm reduction messages should account for the multiple functions benzodiazepines serve in a drug-using context, and encourage drug users to tailor their endorsement of benzodiazepines to peers to include safer alternatives.     

Inappropriate benzodiazepine use in older adults and the risk of fracture

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Benzodiazepine use increases the risk of fracture in the elderly.
• It is controversial which conditions of use are most risky, e.g. use of short- or long-acting benzodiazepines, dose and duration of use.
• The well-known Beers criteria include statements about inappropriate benzodiazepine use in elderly and the risk of fracture, but their clinical value has never been tested in an outcome study.

WHAT THIS STUDY ADDS

• Inappropriate benzodiazepine use according to the Beers criteria is not associated with an increased risk of fracture.
• Daily dose and duration of use is associated with higher risk of fracture, not the type of benzodiazepine prescribed as the Beers criteria state.

AIMS

The Beers criteria for prescribing in elderly are well known and used for many drug utilization studies. We investigated the clinical value of the Beers criteria for benzodiazepine use, notably the association between inappropriate use and risk of fracture.

METHODS

We performed a nested case–control study within the Rotterdam Study, a population-based cohort study in 7983 elderly. The proportion of ‘inappropriate’ benzodiazepine use according to the Beers criteria was compared between fracture patients and controls. ‘Inappropriate’ use for elderly implies use of some long-acting benzodiazepines and some intermediate/short-acting ones exceeding a suggested maximum daily dose. Also, alternative criteria were applied to compare the risk of fracture. Cases were defined as persons with incident fracture between 1991 and 2002 who were current benzodiazepine users on the fracture date. Controls were matched on fracture date and were also current benzodiazepine users.

RESULTS

The risk of fracture in ‘inappropriate’ benzodiazepine users according to the Beers criteria was not significantly different from ‘appropriate’ users [odds ratio (OR) 1.07, 95% confidence interval (CI) 0.72, 1.60]. However, a significantly higher risk of fracture was found in ‘high dose’ users and a longer duration of use (14–90 days), irrespective of the type of benzodiazepine (OR 3.45, 95% CI 1.38, 8.59).

CONCLUSIONS

These findings suggest that inappropriate benzodiazepine use according to the Beers criteria is not associated with increased risk of fracture. Daily dose and longer duration of use (>14 days) is associated with higher risk of fracture, irrespective of the type of benzodiazepine prescribed.     

Patterns and correlates of benzodiazepine use in the French general population

Objective To investigate the prevalence of current use of benzodiazepines (BZDs) and related drugs in the French general population and factors associated with this use.Methods National cross-sectional telephone survey conducted between 25 April 2001 and 8 May 2001 in a representative sample of non-institutionalized adults of BZD use and duration, prescriber specialty, socio-demographic data and mood and anxiety disorders, using a structured diagnostic interview. Results The prevalence of current use of BZD was 7.5%. It was higher among women (9.7%) than men (5.2%). It increased with age and was higher in the jobless (10.9). Duration of BZD use was more than 6 months in 75.9% of users and increased with age. Of the 711 (17.7%) subjects with at least one mood or anxiety disorder, 122 (17%) used BZD compared with180 (5.5%) of the 3296 subjects without mood or anxiety disorders. In multivariate analysis, factors associated with BZD use were age [odds ratio (OR): 3.6; 95% confidence interval (CI) 2.0–5.6], 6.5 (4.1–10.3) and 10.9 (6.9–17.1), respectively, for ages 35–44 years, 45–59 years and over 60 years compared with below 34 years, female gender (OR: 1.7; 95% CI 1.3–2.1), anxiety only (OR: 2.2; 95% CI 1.5–3.2), mood disorder only (OR: 4.4; 95% CI 2.7–7.1) or both mood and anxiety disorders (OR: 8.8; 95% CI 5.9–12.6). Conclusion Despite precautions, warnings and attempts to limit use, there remains a high proportion of long-term BZD users in the general French population, especially in the elderly. Our findings add to the weight of opinion that messages concerning proper use of BZDs certainly need to be clarified and amplified.     

Psychotropic drug utilization patterns in a metropolitan population

Summary Psychotropic drug intake by a random sample of citizens of the city of Munich aged 30–69 years has been assessed. A 1-week prevalence of 9.3% for all psychotropic drug users was found, benzodiazepines accounting for approximately two-thirds (6.6%) of the users. Two-thirds of drug users were women. Drug use in both sexes increased with age. The doses of benzodiazepines prescribed in most cases were less than 10 mg diazepam equivalent per day. Intake of benzodiazepines in combination with analgesics or alcohol (40 g/day) did not appear to represent a major problem. Multiple logistic regression analysis showed that the number of chronic diseases was the strongest predictor of benzodiazepine intake in men, whereas stress and age determined intake in women. Long-term use seemed to be relatively rare at 11% of all benzodiazepine users, so it was not considered to be a severe public health problem.     

Evaluation of factors influencing medication compliance in inpatient treatment of psychotic disorders

Rationale Short- and long-term compliance to prescribed antipsychotic drugs is of particular concern in regard to medication choice and treatment outcome in the care of psychotic disorders.Objective We evaluated patient-related and treatment-related factors associated with medication compliance in inpatients with a diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder.Methods Within a naturalistic study in seven psychiatric hospitals, individuals with a psychotic disorder were assessed weekly on mental state, social functioning, side effects, and medication compliance. Logistic regression analyses were computed to assess patient and clinical predictors of medication compliance.Results We found a significant association between medication compliance and substance abuse (OR 0.52, CI 0.32–0.85), involuntary admission (OR 0.60, CI 0.41–0.89), history of aggressive behavior (OR 0.57, CI 0.38–0.85), and no school graduation (OR 0.59, CI 0.41–0.86). Individuals with pronounced paranoid or negative symptoms were also less compliant in taking their prescribed medication. There was no association between the initial inpatient antipsychotic medication regime and patients’ compliance. Individuals who switched from a typical to an atypical antipsychotic drug were more compliant than those with their typical antipsychotic drug maintained. Those with higher medication compliance showed significantly greater improvement of their psychiatric symptoms during the inpatient stay.Conclusion Patient-related in addition to disease-related factors may strongly influence medication compliance. Besides more compliance with atypicals supposed by the literature, there may be a higher propensity for atypical drugs to be prescribed to those assumed to be more compliant.     

Adjunctive benzodiazepine treatment of hospitalized schizophrenia patients in Asia from 2001 to 2008

Benzodiazepines are commonly prescribed to patients with schizophrenia in many countries, but as little is known about such treatment in Asia, we evaluated their adjunctive use for 6761 in-patients diagnosed with schizophrenia in nine Asian countries using a cross-sectional study design in 2001, 2004 and 2008. Multivariate logistic regression and multivariate linear regression analyses were performed to assess predictors of benzodiazepine use and dose, respectively. Overall, 54% of the patients received adjunctive benzodiazepines at an average daily dose equivalent to 30.3 mg diazepam, with minor changes over the years sampled. Benzodiazepine use was highest in Taiwan and Japan, lowest in Thailand and China, and was associated with fewer years ill, presence of delusions (OR 1.24), hallucinations (OR 1.22), disorganized speech (OR 1.17), social or occupational dysfunction (OR 1.16), and use of mood stabilizers (OR 3.15), antiparkinsonian (OR 1.79) or antidepressant drugs (OR 1.33), and lower doses of antipsychotics (all p=0.016 to <0.001). Benzodiazepine doses were highest in Taiwan and China, lowest in Korea and Singapore; higher doses were associated with being young, male, physically aggressive, receiving mood stabilizers, and having electroconvulsive treatment (all p=0.019 to <0.001). Benzodiazepine use was associated with neurological and systemic adverse effects. In conclusion, benzodiazepine use was common in Asian patients with schizophrenia. Predictors of benzodiazepine use and dose differed in this population. Critical clinical guidelines should be developed specifically for Asian countries to address sound practices in regard to use of benzodiazepines for psychotic disorders.     

Oxidative and nonoxidative benzodiazepines and the risk of femur fracture. The Systematic Assessment of Geriatric Drug Use Via Epidemiology Study Group

Benzodiazepine use is a well-identified risk factor for falls and the resulting femur fractures in elderly adults. Benzodiazepines not requiring hepatic biotransformation may be safer than agents undergoing oxidation because oxidative activity has been shown to decline with age. The association between the use of either oxidative or nonoxidative benzodiazepines and the risk of femur fracture among elderly adults living in nursing homes was studied. A nested case-control study was conducted using the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) database; the records of 9,752 patients hospitalized for incident femur fracture during the period 1992 to 1996 were extracted, matching by age, gender, state, and index date to the records of 38,564 control patients. Conditional logistic regression models were conducted to estimate the odds ratios (ORs) for femur fracture with adjustment for potential confounders. The adjusted OR for the overall use of benzodiazepines was 1.10 (95% confidence interval [CI], 0.98-1.20); the risk seemed of only slightly greater magnitude for exposure to nonoxidative agents (1.18; 95% CI, 1.03-1.36) than to oxidative benzodiazepines (1.08; 95% CI, 0.95-1.23). Among the latter, the effect was mainly accounted for by the use of agents with a long elimination half-life. A dose relationship was observed exclusively among users of long half-life oxidative benzodiazepines. The risk associated with the use of nonoxidative benzodiazepines showed no relationship to the age of the patients. In contrast, patients aged 85 years or older receiving oxidative benzodiazepines at high dosages or as needed had a two- to three-fold increased risk of femur fracture than did patients in the younger age group. Among older individuals, the use of benzodiazepines slightly increased the risk of femur fracture, mainly irrespective of the metabolic fate of the drug. Our results suggest that the use of nonoxidative benzodiazepines does not carry a lower risk for femur fracture than does the use of oxidative benzodiazepines. However, the latter agents may be associated with a somewhat higher risk of side effects among the oldest old, especially at higher dosages.     

Benzodiazepine drugs in general medical patients.

Data from a hospital-based drug surveillance programme were used to determine how often benzodiazepine drugs were used in general medical wards. Benzodiazepines were the drugs most commonly used as hypnotics and were given to 32% of these patients. Concomitant use of more than one benzodiazepine drug or of benzodiazepines with other psychoactive drugs was common and often irrational. A series of double-blind patient-preference studies comparing various benzodiazepines and a benzodiazepine with an antihistamine showed that for short-term hypnotic effect there were no differences between three common benzodiazepines but elderly patients preferred benzodiazepines to the antihistamine, which produced more undesired effects. These results suggest that currently diazepam is the hypnotic of choice for medical ward inpatients.