Anxiolytic-hypnotic Drugs Research Articles

Trends in the prescribing of psychotropic medications for inpatient children and adolescents, 2000–2010

The objective of this study was to investigate the patterns in prescribing of psychotropic drugs for children and adolescents within the psychiatric department of a general hospital in China. Medical records of 878 patients (0-18 years old) were reviewed in 2000, 2005 and 2010. Patient characteristics, total psychotropic drug use and the proportionate use of each drug class (antipsychotics, antidepressants, mood stabilizers and anxiolytic-hypnotic drugs) were analysed. The results indicated that there was a 19.2% increase in the overall use of psychotropic drugs during the study period. The use of selective serotonin reuptake inhibitors increased from 24.8 to 45%, whereas that of tricyclic antidepressants decreased from 17.7 to 0.5%. The use of second-generation antipsychotics increased from 56 to 80%. In contrast, the use of first-generation antipsychotic decreased from 26.2 to 6.5%. The use of valproate also increased significantly from 2.1 to 16.4%. In patients diagnosed with schizophrenia, the use of selective serotonin reuptake inhibitors increased from 1.2 to 18.9% and that of valproate increased from 0 to 12.6%. The increasing trends in psychotropic drug use necessitate addition research to confirm their safety and efficacy in this specific population.

Plasma monitoring: a challenge for and of the laboratory

Introduction: Therapeutic drug monitoring (TDM) of psychiatric patients is advisable, with the aim of reducing side effects and optimizing the therapy, and is a particularly useful tool if one considers the poor compliance of treated patients. Starting from clinical-chemical correlation data, TDM allows therapy personalization according to the specific needs of the patient. This in turn leads to increased patient compliance and to improved drug efficacy, and finally also to lower total treatment expenses, due to the reduction in hospitalisation length and frequency [1]. Methods: Performing the TDM obviously requires suitable analytical methods, consisting in two steps: sample pre-treatment and instrumental analysis. The first step is critical for the removal of biological interferences. The second step is usually carried out by liquid chromatography or capillary electrophoresis, coupled with different detectors, selected on the basis of the drug physico-chemical properties and expected plasma levels. Therefore, the methods and the corresponding techniques should possess adequate sensitivity and selectivity for the particular analytical problem. Results: Psychiatric patients are very often subjected to polypharmacy: for example, with antipsychotic and anxiolytic-hypnotic drugs for the treatment of schizophrenia; or with atypical antipsychotics (quetiapine, olanzapine) and antiepileptic agents (lamotrigine, oxcarbazepine) for bipolar disorder [2]. This fact constitutes a great challenge for both psychiatrists and analytical laboratories. Conclusions: The possibility of unwanted drug interactions is a constant threat during polypharmacy. Drug metabolism can be strongly influenced by the administration of other drugs, leading to possible toxicity, when a reduced metabolism is observed, or to a lack of response to therapy in the opposite case. The presence of numerous drugs and metabolites in the patient plasma makes the analytical problem, as well as the interpretation of the resulting plasma level data, much more complicated. At the same time, it is exactly this kind of challenge that makes it so exciting and interesting to work on plasma monitoring.

Metabolism of Benzodiazepine and Non-Benzodiazepine Anxiolytic-Hypnotic Drugs: an Analytical Point of View

A review with 132 references. Several kinds of anxiolytic and hypnotic drugs are currently available on the market. Although BZDs are surely the most frequently prescribed among them, several chemically unrelated compounds have been commercialised, which can provide similar or even higher efficacy and tolerability. These drugs can prove useful for patients who are non-responder or intolerant to benzodiazepine treatment, thus giving broader therapeutic options to the clinician. The most important studies on the metabolic characteristics of several non-benzodiazepine anxiolytics and hypnotics are reported and briefly discussed in this review; moreover, the analytical methods related to these studies are also described and commented upon and their characteristics are highlighted. Finally, an update is included on recent (2007-2010) metabolism and pharmacokinetic studies on benzodiazepines. A monograph is included for each of the following drugs: zolpidem, zaleplon, zopiclone, ramelteon, buspirone and tandospirone; updates are included for the following benzodiazepines: alprazolam, bromazepam, diazepam, flunitrazepam, lorazepam, midazolam, oxazepam and triazolam.

Antidepressant Use in Elderly Suicide Victims in New York City

We examined postmortem evidence of antidepressant, analgesic, and anxiolytic-hypnotic drugs in suicide victims aged 65 years and older. We assessed data on Medical Examiner-certified suicide victims aged 65 years or older from 2001 through 2004 who had resided and died in New York City and who underwent toxicologic investigation for antidepressant, analgesic, and anxiolytic-hypnotic drugs. We calculated annual population-based suicide rates and rates of positive toxicologic findings for each of the 3 classes of medications across 3 age strata: 65 to 74, 75 to 84, and 85 years and older. There were 255 certified suicide victims among New York City residents aged 65 years or older from 2001 through 2004. Results of toxicologic testing were available for 63.5% (162) of suicide victims. Antidepressants were detected in 22.0% of suicide victims aged 65 to 74 years, 26.8% of those aged 75 to 84 years, and 16.7% of those aged 85 years and older. The oldest age stratum had both the highest suicide rates in the over-65-years population at 10.7 per 100,000 and the lowest percentage of antidepressant use among all geriatric suicide victims. Rates of detection of antidepressant medication were low for all geriatric suicide victims, especially the oldest. Analgesics and anxiolytic-hypnotics may have been taken in lieu of antidepressants by suicide victims aged 85 years and older. Assuming that many of the suicide victims had clinically treatable depression, these findings implicate problems in the delivery of specific antidepressant pharmacologic treatment to the "old-old."

Trends in the Use of Psychotropic Drugs in Taiwan: A Population-Based National Health Insurance Study, 1997-2004

Trends in the Use of Psychotropic Drugs in Taiwan: A Population-Based National Health Insurance Study, 1997-2004

Trends in the Use of Psychotropic Drugs in Taiwan: A Population-Based National Health Insurance Study, 1997–2004

This study examined changes in the use of psychotropic agents in Taiwan between 1997 and 2004. The population-based National Health Insurance database was used to detect trends in the use of psychotropic drugs in Taiwan. A dynamic random sample of 200,432 persons was gathered and followed from 1997 to 2004. Persons in the sample who had made at least one service claim during these years for either ambulatory or inpatient care with a psychotropic drug prescription were identified. The prevalence of any psychotropic drug use increased from 7.1% in 1997 to 12.0% in 2004. The changes in prevalence of use of four kinds of psychotropic drugs from 1997 to 2004 were as follows: antipsychotics, 3.4% to 3.7%, although this finding was not significant; antidepressants, 2.2% to 4.4% (p<.001); mood stabilizers, .6% to 1.3% (p<.001); and anxiolytic-hypnotic drugs, 3.0% to 7.3% (p<.001). Overall, the prevalence of use of three kinds of psychotropic drugs (antidepressants, mood stabilizers, and anxiolytic-hypnotic drugs) increased greatly from 1997 to 2004.

Neighborhood social participation, use of anxiolytic-hypnotic drugs, and women's propensity for disability pension: a multilevel analysis

The increasing number of people on disability pension in Sweden is of concern for Swedish policy-makers, and there is a need for a better understanding of the mechanisms behind disability pension. We investigated (i) whether women living in the same neighborhood have a similar propensity for disability pension that relates to neighborhood social participation, and (ii) whether there is an association between anxiolytic-hypnotic drug (AHD) use and disability pension in women that is modified by the neighborhood context. We used multilevel logistic regression with 12,156 women aged 45 to 64 (first level) residing in 95 neighborhoods (second level) in the city of Malmö (250,000 inhabitants), Sweden, who participated in the Malmö Diet and Cancer Study (1991-96). Both AHD use (OR = 2.09, 95% CI 1.65, 2.65) and neighborhood rate of low social participation (OR = 11.85, 95% CI 5.09, 27.58) were associated with higher propensity for disability pension. The interval odds ratio indicated that the influence of neighborhood social participation was large compared with the unexplained variance between the neighborhoods. The association between AHD use and disability pension was not modified by the neighborhood context. The median odds ratio was 1.44 after adjusting for individual characteristics and 1.27 after the additional adjusting for neighborhood social participation. Women living in the same neighborhood appear to have a similar propensity for disability pension, beyond individual characteristics, and this contextual effect seems largely explained by neighborhood social participation. In addition, AHD use might increase the propensity for disability pension in women.

Anxiolytic–hypnotic drug use associated with trust, social participation, and the miniaturization of community: A multilevel analysis

The concept of social capital has gained wide interest in public health research in recent years. However, we suggest a concept that was introduced and developed by Fukuyama, named “miniaturization of community”, as an alternative to that of social capital. The concept of miniaturization of community emphasizes that a high level of social participation can be accompanied by a low level of trust, both at the individual and at the community level, which may in turn result in social disorder and lack of social cohesion. When society becomes more disordered, people may tend to feel more insecure and anxious. Use of anxiolytic–hypnotic drugs (AHDs) could under such circumstances be a coping strategy. In this study, we first wanted to investigate whether the contextual component of the miniaturization of community concept (i.e. area high social participation and low trust) is associated with individual AHD use, over and above individual characteristics. Secondly, we aimed to study whether people living in the same municipality share a similar probability of AHD use, after adjusting for individual characteristics, and if so, how large this contextual phenomenon is. We used data on 20,319 women and 17,850 men aged 18–79 years from 58 municipalities in six regions in central Sweden, who participated in the Life & Health year 2000 postal survey. We applied multilevel logistic regression analysis with individuals at the first level and areas at the second level. Our results suggest that living in an area with a high level of miniaturization of community seems to be associated with individual AHD use, beyond people's individual characteristics including their own level of social participation and trust. The concept of miniaturization of community may be an extension of the classic concept of social capital and may increase our understanding of contextual effects on health.

GABA A-receptor plasticity during long-term exposure to and withdrawal from progesterone

The subunit composition of native gamma-aminobutyric acid type A (GABAA) receptors is an important determinant of the role of these receptors in the physiological and pharmacological modulation of neuronal excitability and associated behavior. GABAA receptors containing the alpha 1 subunit mediate the sedative-hypnotic effects of benzodiazepines (Rudolph et al., 1999; McKernan et al., 2000), whereas the anxiolytic effects of these drugs are mediated by receptors that contain the alpha 2 subunit (Löw et al., 2000). In contrast, GABAA receptors containing the alpha 4 or alpha 6 subunits are insensitive to benzodiazepines (Barnard et al., 1998). Characterization of the functions of GABAA-receptors thus requires an understanding of the mechanisms by which the receptor subunit composition is regulated. The expression of specific GABAA-receptor subunit genes in neurons is affected by endogenous and pharmacological modulators of receptor function. The expression of GABAA-receptor subunit genes is thus regulated by neuroactive steroids both in vitro and in vivo. Such regulation occurs both during physiological conditions, such as pregnancy, and during pharmacologically induced conditions, such as pseudo-pregnancy and long-term treatment with steroid derivatives or anxiolytic-hypnotic drugs. Here, we summarize results obtained by our laboratory and by other groups pertaining to the effects of long-term exposure to, and subsequent withdrawal from, progesterone and its metabolite 3 alpha,5 alpha-tetrahydroprogesterone on both the expression of GABAA-receptor subunits and GABAA-receptor function.

Mortality in elderly men with low psychosocial coping resources using anxiolytic - hypnotic drugs

Insufficient coping with stress may lead to increased susceptibility for disease and death. Use of anxiolytic-hypnotic drugs has been suggested as a coping strategy, and some opinions have proposed their use as preventive medication. The aim of this study was to estimate if use of anxiolytic-hypnotic drugs counters the increased mortality observed in individuals lacking other coping strategies such as emotional support and social participation. A population based cohort study with 10-year (1982/83-1993) survival analysis was performed in 491 men born in 1914, living in the Swedish city of Malmö. Compared with men with a high level of psychosocial coping resources who did not use anxiolytic-hypnotic drugs, men with a low level of psychosocial coping resources had a higher risk of death irrespective whether they used anxiolytic-hypnotic drugs, RR = 1.7 (95% CI 1.1-2.6) or not RR = 1.8 (95%: 1.3-2.5). Anxiolytic-hypnotic drugs do not seem to counter increased mortality in elderly men with low psychosocial coping resources.

Mortality in elderly men with low psychosocial coping resources using anxiolytic-hypnotic drugs

Mortality in elderly men with low psychosocial coping resources using anxiolytic-hypnotic drugs

Impaired cognitive function in elderly men exposed to benzodiazepines or other anziolytics

A representative sample of 68 year old men living in Malmo, Sweden, was investigated concerning use of anxiolytic-hypnotic drugs. The subjects were psychometrically tested using the synonyms, Koh's block design, paired associates, visual retention, and digit symbol tests. Subjects with continuous use of anxiolytics, the vast majority of which consisted of benzodiazepines, had an increased risk of impaired cognitive function (RR=3.2 and p=0.008). Multivariate adjustments for differences in education, alcohol habits, exposure to organic solvents and stroke between users and non-users of anxiolytics did not reduce the estimate of risk (RR adj =3.4; 95% confidence interval: 1.3–8.9). Adjusting for differences in the number of subjects with a history of depression reduced the risk estimate slightly (RR adj =2.7; 95% confidence interval: 1.0–7.7) but adjustments for differences in anti-hypertensive and anti-diabetic medication had no influence. Subjects with occasional use of anxiolytics and subjects with occasional or continuous use of hypnotics showed no risk increase. Neither selection bias nor information bias appeared to explain the findings. Accordingly, increased caution is warranted when prescribing benzodiazepines for regular anxiolytic use.

Increased risk of ischaemic heart disease mortality in elderly men using anxiolytics-hypnotics and analgesics. Results of the 10-year follow-up of the prospective population study "Men born in 1914", Malmo, Sweden.

An increased risk of all-cause and cardiovascular mortality in users of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may be an additional factor. Therefore, we examined the association of AHD and analgesic use, alone and in combination, with all-cause and ischaemic heart disease (IHD) mortality. Multivariate 10-year survival analysis in a population based cohort of 500 men born in 1914. Relative risks (RR) were adjusted by relevant confounders (blood pressure, serum cholesterol, diabetes mellitus, smoking habit, high alcohol consumption, history of previous IHD, cancer, and other diseases). The RR of both all-cause and IHD mortality were significantly increased among those using both AHD and analgesics compared to those who took neither of these drugs: RR = 1.8 for all-cause mortality, and RR = 2.7 for IHD mortality. Although the number of cases was small, warranting interpretative caution, the current study suggests that the combined use of AHD (mainly benzodiazepines) and analgesics seems to be associated with an increase in all-cause and IHD mortality in elderly men.

Anxiolytic-hypnotic drugs: Relationships between prescribing, abuse and suicide

In 1978 the third largest Swedish city, Malmö, known to have the highest suicide frequency in the country, was found to have a higher prescription rate (defined daily doses (DDD) per 1,000 inhabitants per day) of anxiolytic-hypnotic drugs (AHD) than the country, the corresponding county, other counties, and other cities, including the largest (Stockholm) and second largest (Göteborg = Gothenburg) cities. Barbiturate prescribing in Malmö was 40% higher than in Stockholm and 90% higher than in Göteborg, and the frequency of suicide due to barbiturates was three-times higher than in Göteborg. A small proportion (2.4% of all AHD-prescribing doctors) of private practitioners wrote a large percentage (24%) of all AHD prescriptions. Prescription surveillance and an information campaign in Malmö were accompanied by a 4-year decrease in AHD prescribing (12%), in AHD abuse (40%), in barbiturate prescribing (45%), and in barbiturate suicides (70%). The total suicide rate was reduced by 25%. There was no corresponding 4-year increase in suicide due to other drugs, or by other means, but after 5 to 7 years there was an increase in suicide by non-pharmacological means. The contribution of benzodiazepines to the frequency of suicide was very small, whereas their contribution to AHD abuse was considerable. In Göteborg, where no corresponding intervention was carried out, there was also a reduction in barbiturate prescribing (34%) and in barbiturate suicides (45%), but in contrast there was a continuous increase both in overall AHD and benzodiazepine prescribing, surpassing Malmö after 5 years. Far from a reduction there was a 7-year increase in the overall frequency of suicide. Apparently, AHD abuse and suicide can be greatly reduced by restricted prescribing of AHD, and this may but need not be accompanied by an increase in suicide by other means. Targeted drug information campaigns may assist in changing prescription patterns and their medical and social impact.