Cigarette and e-cigarette use trajectories and prospective prescription psychotherapeutic drug misuse among adolescents and young adults.

OBJECTIVE: This study aimed to determine the potential longitudinal impact of different cigarette and e-cigarette use trajectories among people aged 10-24 on prescription drug misuse of psychotherapeutic drugs. METHODS: Data came from waves 1-5 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2019; n = 14,454). Group-based trajectory modeling identified groups of adolescents and young adults based on cigarette and e-cigarette use across the five waves. Weighted logistic regression models were fit to examine the association of group membership with two outcomes at all waves: 1) misuse of opioids, sedatives, and/or tranquilizers, and 2) misuse of Ritalin and/or Adderall, adjusting for background characteristics. RESULTS: Five trajectory groups emerged: (1) non-use (77.7 %); (2) early-onset cigarette use with reducing use (4.6 %); (3) ever-increasing e-cigarette use (6.1 %); (4) stable dual use of cigarettes and e-cigarettes (3.2 %); and (5) accelerating dual use of cigarettes and e-cigarettes (8.4 %). In comparison to the non-use group, all other groups had significantly higher odds of misuse of opioids, tranquilizers, and/or sedatives and all but the early-onset cigarette use with reducing use group had significantly higher odds of misuse of Ritalin and/or Adderall by the end of wave 5. DISCUSSION: Patterns of cigarette and e-cigarette use in adolescent and young adult populations may serve as important indicators for concurrent and prospective prescription psychotherapeutic drug misuse. Findings highlight the need for cigarette and e-cigarette use prevention, harm reduction, and/or cessation efforts among adolescents and young adults.

Prescription Psychotherapeutic Drug Use and Nicotine Use among Young People in the United States.

Background: While prescription psychotherapeutic drug use (PPDU) and nicotine use pose substantial problems in isolation, they pose an increased risk in combination. This study aimed to estimate the prevalence of PPDU for young people, stratified by nicotine use status. A trend analysis was used to examine changes in PPDU and nicotine use over time. Methods: We used a cross-sectional population-based sample of young people aged 16-25 years (n = 10,454) from the National Health and Nutrition Examination Survey (NHANES, 2003-2018). For each data cycle, the prevalence of self-reported PPDU and nicotine including pain relievers, sedatives, stimulants, and tranquilizers was estimated. Using Joinpoint regression, we tested for significant changes in trends using a log-linear model and permutation test approach and produced the average data cycle percentage change (ADCPC). Results: From 2003 to 2018, 6.7% of young people had PPDU and 27.3% used nicotine. The prevalence of cigarette smoking decreased while other nicotine product use increased (p's < 0.001). Those who used nicotine were more likely to have PPDU (8.2%; 95% CI = 6.5%, 9.8%) vs. non-nicotine use (6.1%; 95% CI = 5.1%, 7.0%; p = 0.01). Results indicated a decreasing trend for nicotine use (ADCPC = -3.8, 95% CI = -7.2, -0.3; p = 0.04), but not for PPDU (ADCPC = 1.3; 95% CI = -4.7, 7.8; p = 0.61). On further examination, opioid use decreased, sedative use remained stable, and stimulant and tranquilizer use increased over time. Conclusions: From 2003 to 2018, young people who used nicotine had a higher prevalence of PPDU than those who did not. Clinicians should communicate the association between nicotine use and prescription drugs when prescribing or managing young patients' medications.

Prevalence of the Consumption of Tranquilizers without a Medical Prescription and Associated Factors in School-Based Adolescents in Colombia / Prevalencia del consumo de tranquilizantes sin prescripción médica y factores asociados en adolescentes escolarizados de Colombia / Prevalência do uso de tranquilizantes sem prescrição médica e fatores associados em adolescentes em idade escolar na Colômbia

Introduction: Non-prescription tranquilizers are a specific group of benzodiazepines, used as drugs that act on the central nervous system and have an extensive effect in patients with anxiety disorders and problems in sleep stages. Objective: To determine the prevalence of the year and month of consumption of tranquilizers without a medical prescription and the associated factors, in adolescents in school in Colombia. Methods: It is a cross-sec-tional study with an analytical scope. The universe of the study consisted of 3,243,377 students, from grades 7 to 11 (aged between 12 and 18 years), the valid surveys were 80,018. The adolescent who declared having used tranquilizers during the last 30 days and the last 12 months was considered a consumer. All variables were self-re-ported by adolescents. Results: The prevalence of tranquilizer use without medical prescription was 1.02% and 1.97% (month and year, respectively). Adolescents who presented disciplinary problems are the most predisposed to use during the last month with an OR 2.79 (95% CI: 2.20­3.53) and last year an OR of 2.77 (95 % CI: 2.34­3.27). Conclusions: There is a higher prevalence of the consumption of tranquilizers without medical prescription in women between 14 and 17 years of age, from mixed schools and it is associated with academic and disciplinary performance problems, in the last year. In addition, as age increases, the consumption of substances without a medical prescription increases

Introducción: Los tranquilizantes sin prescripción médica son un grupo específico de benzodiacepinas, usados como medicamentos que actúan sobre el sistema nervioso central y cuentan con un extenso efecto en pacientes con trastornos de ansiedad y problemas en las etapas del sueño. Objetivo: Determinar la prevalencia de año y mes de consumo de tranquilizantes sin prescripción médica y los factores asociados en adolescentes escolarizados de Colombia. Métodos: Estudio transversal con alcance analítico. El universo del estudio estuvo constituido por 3 243 377 estudiantes de los gados 7.º a 11.º (con edades entre 12 y 18 años). Las encuestas válidas fueron 80 018. Se consideró consumidor al adolescente que declaró haber consumido tranquilizantes durante los últimos 30 días y los últimos 12 meses. Todas las variables fueron autorreportadas por los adolescentes. Resultados: La prevalencia de consumo de tranquilizantes sin prescripción médica fue del 1,02 % y del 1,97 % (mes y año, respectivamente). Los adolescentes que presentaron problemas disciplinarios son los más predispuestos al consumo durante el último mes con un OR de 2,79 (IC95 %: 2,20-3,53) y último año un OR de 2,77 (IC95 %: 2,34-3,27). Conclusiones: Existe mayor prevalencia de consumo de tranquilizantes sin prescripción médica en mujeres entre los 14 y los 17 años, de colegios mixtos, y se encuentra asociada con problemas de rendimiento académico y disciplinarios, en el último año. Además, a medida que aumenta la edad, se incrementa el consumo de sustancias sin prescripción médica

Introdução: Os tranquilizantes isentos de prescrição são um grupo específico de benzodiazepínicos, usados como medicamentos que atuam no sistema nervoso central e têm um efeito extenso em pa-cientes com transtornos de ansiedade e problemas no estágio do sono. Objetivo: Determinar a prevalência anual e mensal do uso de tranquilizantes sem prescrição médica e os fatores associados em adolescentes em idade escolar na Colômbia. Métodos: Estudo transversal com escopo analítico. O universo do estudo consistiu em 3243377 alunos da 7ª à 11ª série (com idades entre 12 e 18 anos). Foram realizadas 80018 pesquisas válidas. Um adolescente foi considerado usuário, o qual relatou ter usado tranquilizantes nos últimos 30 dias e nos últimos 12 meses. Todas as variáveis foram autorrelatadas pelos adolescentes. Resultados: A prevalência do uso de tranquilizantes sem prescrição médica foi de 1,02% e 1,97% (mês e ano, respectivamente). Os adolescentes com problemas disciplinares apresentaram maior pro-babilidade de uso no último mês, com um OR de 2,79 (IC95%: 2,20-3,53) e no último ano, com um OR de 2,77 (IC95%: 2,34-3,27). Conclusões: Há uma maior prevalência de uso de tranquilizantes sem prescrição médica em mulheres de 14 a 17 anos, de escolas mistas, e isso está associado a problemas de desempenho acadêmico e disciplinar no último ano. Além disso, com o aumento da idade, aumenta o uso de substâncias sem prescrição médica.

Effect of Valproic Acid on the Metabolic Spectrum of Clozapine in Patients With Schizophrenia.

BACKGROUND: Valproic acid (VPA) is frequently used with clozapine (CLZ) as mood stabilizer and/or seizure prophylaxis. Valproic acid is known to reduce N-desmethylclozapine (N-DMC) but not CLZ levels. This leads to the hypothesis that VPA induces the CLZ metabolism via non-N-desmethylation pathways. Therefore, we aimed to investigate the effect of concurrent VPA use on the serum concentrations of a spectrum of CLZ metabolites in patients, adjusting for smoking. METHODS: In total, 288 patients with an overall number of 737 serum concentration measurements of CLZ and metabolites concurrently using VPA (cases, n = 22) or no interacting drugs (controls, n = 266) were included from a routine therapeutic drug monitoring service. Linear mixed model analyses were performed to compare the dose-adjusted concentrations (C/D) of CLZ, N-DMC, CLZ 5N/N+-glucuronides, and metabolite-to-parent ratios in cases versus controls. RESULTS: After adjusting for covariates, the N-DMC (-40%, P < 0.001) and N+-glucuronide C/Ds (-78%, P < 0.001) were reduced in cases versus controls, while the CLZ C/D was unchanged (P > 0.7). In contrast, the 5N-glucuronide C/D (+250%, P < 0.001) and 5N-glucuronide-to-CLZ ratios (+120%, P = 0.01) were increased in cases versus controls. CONCLUSIONS: Our findings show that complex changes in CLZ metabolism underly the pharmacokinetic interaction with VPA. The lower levels of N-DMC seem to be caused by VPA-mediated induction of CLZ 5N-glucuronide formation, subsequently leading to reduced substrate availability for N-desmethylation. Whether the changes in CLZ metabolism caused by VPA affects the clinical outcome warrants further investigation.

The latent class structure of substance use in US adults 50 years and older.

OBJECTIVE: Substance use rates have increased in adults 50 years and older, and substance use in this population is associated with significant consequences. Given that little is known about their underlying substance use patterns, the objective was to identify latent classes of adults 50 years and older by past-year substance use, past-month substance use, and past-year substance use disorder (SUD) diagnosis. METHODS: The National Survey on Drug Use and Health is an annual nationwide cross-sectional U.S. survey. Participants were 35,229 civilian, non-institutionalized U.S. residents, 50 years and older. Past-year and past-month alcohol, tobacco, marijuana, heroin, cocaine, methamphetamine use, and opioid, stimulant, and tranquilizer/sedative prescription drug misuse (PDM) were captured, as was past-year DSM-IV SUD from these substances. Correlates included mental health, physical health, and healthcare utilization variables. RESULTS: Latent class analysis indicated four past-year or past-month substance use subgroups (Alcohol-Only, Alcohol-Tobacco-Marijuana, Cocaine-Polydrug, PDM-Polydrug), with SUD prevalence rising from 3.2% to 17.3%, 68.8%, and 78.5% by past-year subgroup; similarly, rates of past-year suicidal ideation increased from 2.1%, to 4.8%, 12.0%, and 20.4% by past-year subgroup. For SUD, there were three subgroups (Low Nicotine Dependence [ND], High Alcohol Use Disorder, Multiple SUDs). Over 90% of adults were in a low-risk subgroup (i.e., Alcohol-Only and Low ND), but members of Cocaine-Polydrug, PDM-Polydrug, or Multiple SUDs latent classes had high rates of mental and physical health concerns. CONCLUSIONS: Most adults 50 and older have lower risk profiles, but those engaged in PDM or cocaine use are heavily substance-involved and need screening and likely multi-disciplinary intervention.

ß-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice.

Anxiety and stress-related conditions represent a significant health burden in modern society. Unfortunately, most anxiolytic drugs are prone to side effects, limiting their long-term usage. Here, we employ a bioinformatics screen to identify drugs for repurposing as anxiolytics. Comparison of drug-induced gene-expression profiles with the hippocampal transcriptome of an importin α5 mutant mouse model with reduced anxiety identifies the hypocholesterolemic agent ß-sitosterol as a promising candidate. ß-sitosterol activity is validated by both intraperitoneal and oral application in mice, revealing it as the only clear anxiolytic from five closely related phytosterols. ß-sitosterol injection reduces the effects of restraint stress, contextual fear memory, and c-Fos activation in the prefrontal cortex and dentate gyrus. Moreover, synergistic anxiolysis is observed when combining sub-efficacious doses of ß-sitosterol with the SSRI fluoxetine. These preclinical findings support further development of ß-sitosterol, either as a standalone anxiolytic or in combination with low-dose SSRIs.

N-Acetylcysteine Augmentation for Patients With Major Depressive Disorder and Bipolar Depression.

Major depressive disorder (MDD) and bipolar depression (BD) can often be difficult to treat. N-acetylcysteine (NAC) is a nutraceutical product that has been trialed in a large number of neuropsychiatric and medical disorders, with mixed results. Many randomized controlled trials (RCTs) have studied NAC augmentation as an intervention in MDD and BD. These RCTs were pooled in 2 recent meta-analyses. One meta-analysis with 7 RCTs (pooled N = 728) conducted in patients with MDD or BD found that NAC was not superior to placebo in the attenuation of depression ratings in either main or sensitivity analyses. The other meta-analysis with 6 RCTs (pooled N = 248) conducted in patients with BD found a small, imprecise effect size for NAC (standardized mean difference, 0.45; 95% confidence interval, 0.06-0.84). The advantage for NAC in this meta-analysis would almost certainly have been lost had the authors excluded from analysis 2 RCTs, both of which had problematic characteristics and findings and both of which also obtained a large and statistically significant advantage for NAC. At present, therefore, evidence does not encourage the use of NAC as an augmentation treatment for patients with MDD or BD. It remains to be seen whether NAC augmentation benefits depressed subpopulations, such as those with higher levels of inflammatory biomarkers at baseline.

Exploración del efecto de Trichocereus pachanoi en el carácter depresivo en ratas / Exploring the effect of Trichocereus pachanoi on the depression-like behavior in rats

Introducción: Existen plantas que se usan desde tiempos ancestrales con efecto alucinógeno y alteraciones al sistema nervioso central, debido a la presencia principalmente de mezcalina son usadas para cumplir objetivos tradicionales asociados a la adivinación, curandería, divinidad y otros. Objetivos: Determinar el efecto del extracto acuoso de Trichocereus pachanoi a dosis de 10 por ciento, 20 por ciento y 30 por ciento sobre el comportamiento exploratorio de carácter depresivo en Rattus rattus var. albinus. Material y métodos: El presente estudio experimental es de carácter exploratorio aplicado, constructivo y prospectivo, se formaron 4 grupos de 10 ratas cada uno a las que se les administró extracto acuoso de Trichocereus pachanoi en dosis creciente, luego fueron sometidas a natación forzada con entrenamiento previo de 15 minutos. Resultados: El grupo que no recibió tratamiento alguno posee la más baja respuesta en gasto de tiempo para el escalamiento, comparado con los grupos B, C y D que presentan 13,5 min. 17,17 min. y 24,37 min. respectivamente. También en la evaluación de la movilidad, el grupo A posee en valor más bajo, comparado con los grupos B, C y D que presentan 13,42 min. 17,62 min. y 23,12 min., respectivamente. Conclusiones: El tratamiento en ratas con extracto acuoso de Trichocereus pachanoi a concentraciones de 10 por ciento, 20 por ciento y 30 por ciento ha sido eficaz en producir un efecto tranquilizante en el comportamiento exploratorio de carácter depresivo en el sujeto(AU)

Introduction: Since ancient times, some mescaline containing plants that have hallucinogen effects and cause alterations in the central nervous system have been used to fulfill traditional objectives associated with divination, healing, spirituality and others. Objective: To determine the effect of the aqueous extract of Trichocereus pachanoi at doses of 10 %, 20 % and 30 % solution on depression-like exploratory behavior in Rattus rattus var. albinus. Material and Methods: The present experimental study, which is exploratory, constructive and prospective in nature, was conducted in 4 groups of 10 rats. The rats were administered increasing doses of aqueous extract of Trichocereus pachanoi; then, they underwent forced swimming with a previous 15-minute training. Results: The group that did not receive any treatment had the lowest response to the duration of time spent at scaling compared to groups B, C and D that spent 13.5 min., 17.17 min., and 24.37 min., respectively. Also, in the evaluation of mobility, group A showed the lowest value compared to groups B, C and D that recorded 13.42 min., 17.62 min., and 23.12 min., respectively. Conclusions: The treatment with aqueous extract of Trichocereus pachanoi at concentrations of 10 percent, 20 percent and 30 percent applied to rats has been effective in producing a tranquilizer effect on the depression-like exploratory behavior in rats(AU)

Effect of Metabolic Syndrome on Blood Pressure Changes During Cataract Surgery.

PURPOSE: To investigate effect of metabolic syndrome on blood pressure during cataract surgery with topical anesthesia. DESIGN: A single-centered, retrospective case series. METHODS: Consecutive patients who were hospitalized and underwent phacoemulsification and insertion of intraocular lens with topical anesthesia in October 2016 were included. Perioperative blood pressure and pulse pressure were compared between patients with metabolic syndrome (metabolic group) and sex- and age-matched patients without metabolic syndrome (nonmetabolic group) at six time points: on admission, in the morning of the operation, 2 hours before the operation, at the point of entering the operation room, during the operation, and after the operation. Perioperative use of etizolam and nicardipine was compared between the two groups. RESULTS: Thirty patients in the metabolic group and 30 in the nonmetabolic group were included. There was no difference in changes compared with the values on admission in systolic pressure and pulse pressure at any examination point between the two groups. There was no difference in changes in diastolic pressure between the two groups, except for at 2 hours before the operation (1.4 ±â€Š9.6 mm Hg in the metabolic group vs -6.2 ±â€Š8.5 mm Hg in the nonmetabolic group; P = 0.044). The number of patients who were administered etizolam was 5/30 (16.7%) in the metabolic group and 2/30 (6.7%) in the nonmetabolic group, showing no significant difference. No patients were administered intravenous nicardipine in either group. CONCLUSIONS: Well-controlled metabolic syndrome did not affect the changes in perioperative blood pressure during cataract surgery with topical anesthesia.

Gender differences in the nonmedical use of psychoactive medications in the school population- national trends and related factors.

BACKGROUND: The nonmedical use of prescribed medicines among adolescents has increased significantly in recent years. Our study was designed to describe the prevalence of the nonmedical use of tranquilizers, sedatives, and sleeping pills (TSSp) among the school-age population residing in Spain from a gender perspective, and to identify factors associated with such use. METHODS: Nationwide, epidemiological, cross-sectional study on the nonmedical use during the previous 30 days, of TSSp by the Spanish school population. We used individualized secondary data retrieved from the 2004, 2006, 2008, 2010, 2012 and 2014 Spanish state survey on Drug Use in Secondary Education and a total of 179,114 surveys from respondents aged 14 to 18 years. Using logistic multivariate regression models, we estimated the independent effect of each of these variables on the nonmedical use of medicines. Two models were generated- one for females and one for males. RESULTS: 2.86% (5116) of the Spanish school population of both sexes made nonmedical use of TSSp. Prevalence was greater among girls than among boys for all the study years. Patterns of nonmedical use among female adolescents were related to alcohol, tobacco and marijuana use. Consumption of illegal psychoactive substances, other than marijuana, was the variable showing the greatest value among male teenagers (aOR 6.21 (95% CI 4.97-7.77). CONCLUSIONS: The prevalence of the nonmedical use of TSSp is higher in girls than in boys. The influence of legal and illegal psychoactive substances leads to a higher likelihood of nonmedical use of TSSp in high-school students in Spain.

Time Trends in the Co-use of Cannabis and the Misuse of Tranquilizers, Sedatives and Sleeping Pills among Young Adults in Spain between 2009 and 2015.

The aims of this study were: (a) to estimate time trends in the prevalence of the co-use of cannabis and other cannabis-based products (CBP) with the misuse of tranquilizers, sedatives, and sleeping pills (TSSp) between 2009 and 2015; and (b) to identify the factors associated with the probability of the co-use of CBP with TSSp misuse during this period among Spanish younger adults (15-34 years old). We analyzed data collected from the Spanish National Surveys on Alcohol and Other Drugs (EDADES) in 2009, 2011, 2013, and 2015. CBP co-use with TSSp misuse were the dependent variables. We also analyzed sociodemographic features, self-perceived health status, lifestyle habits, perceived health risk of consumption, and perceived availability of substance using logistic regression models. The prevalence of CBP co-use with TSSp misuse has decreased in Spain. The factors associated with co-use were a lack of education (OR 2.34), alcohol (OR 7.2), tobacco (OR 6.3) and other illicit psychoactive drug (OR 6.5) consumption, perceived non-health risk for the consumption of CBP and TSSp (OR 3.27), and perceived availability of CBP (OR 2.96). Our study identified several factors that appear to affect CBP and TSSp co-use in younger adults, with potential implications for healthcare providers.

Variable reduction for past year alcohol and drug use in unmet need for mental health services among US adults.

BACKGROUND: No previous study has focused on the inter-relationship among alcohol and drug use variables in the past year. This study aimed to classify the past year alcohol and drug use variables and investigate the selected variables in past year alcohol and drug use with the unmet need for mental health services among US adults. METHODS: Data came from the 2015 National Survey on Drug Use and Health (NSDUH). Oblique principal component cluster analysis (OPCCA) was used to classify 37 variables on alcohol and drug use in the past year into disjoint clusters. Weighted multiple logistic regression analysis was used to examine the associations of selected variables with the unmet need. RESULTS: 37 alcohol and drug use variables were divided into 7 clusters. The variable with the lowest 1-R2 ratio (R2 is the squared correlation) from each cluster was selected as follows: tobacco use, pain reliever use, tranquilizer use, stimulant use, zolpidem products use, illicit drug and alcohol use, and benzodiazepine tranquilizers misuse. Multiple logistic regression analysis showed that pain reliever use (OR = 1.33, 95% CI = 1.17-1.50), tranquilizer use (OR = 2.49, 95% CI = 2.16-2.86), stimulant use (OR = 1.22, 95% CI = 1.01-1.47), and illicit drug and alcohol use (OR = 1.54, 95% CI = 1.34-1.77) revealed positive associations with the unmet need for mental health services. CONCLUSION: This is the first study using OPCCA to reduce the dominations of alcohol and drug use; several alcohol and drug use variables in the past year were associated with unmet need of mental health services.

Feline hyperaesthesia syndrome with self-trauma to the tail: retrospective study of seven cases and proposal for an integrated multidisciplinary diagnostic approach.

CASE SERIES SUMMARY: This was a retrospective study on the clinical features and response to treatment in seven cats with feline hyperaesthesia syndrome (FHS) and tail mutilation. FHS is a poorly understood disorder characterised by skin rippling over the dorsal lumbar area, episodes of jumping and running, excessive vocalisation, and tail chasing and self-trauma. The majority of the cats were young, with a median age of 1 year at the onset of clinical signs, male (n = 6) and with access to the outdoors (n = 5). Multiple daily episodes of tail chasing and self-trauma were reported in five cats, with tail mutilation in four cats. Vocalisation during the episodes (n = 5) and rippling of lumbar skin (n = 5) were also reported. Haematology, serum biochemistry, Toxoplasma gondii and feline immunodeficiency virus/feline leukaemia virus serology, MRI scans of brain, spinal cord and cauda equina, cerebrospinal fluid analysis and electrodiagnostic tests did not reveal any clinically significant abnormalities. A definitive final diagnosis was not reached in any of the cats, but hypersensitivity dermatitis was suspected in two cases. A variety of medications was used alone or in combination, including gabapentin (n = 6), meloxicam (n = 4), antibiotics (n = 4), phenobarbital (n = 2), prednisolone (n = 2) and topiramate (n = 2); ciclosporin, clomipramine, fluoxetine, amitriptyline and tramadol were used in one cat each. Clinical improvement was achieved in six cases; in five cats complete remission of clinical signs was achieved with gabapentin alone (n = 2), a combination of gabapentin/ciclosporin/amitriptyline (n = 1), gabapentin/prednisolone/phenobarbital (n = 1) or gabapentin/topiramate/meloxicam (n = 1). RELEVANCE AND NOVEL INFORMATION: This is the first retrospective study on a series of cats with FHS. The diagnostic work-up did not reveal any significant abnormalities of the central or peripheral nervous system; dermatological and behavioural problems could not be ruled out. We propose an integrated multidisciplinary diagnostic pathway to be used for the management of clinical cases and for future prospective studies.

Trends of Polypharmacy and Prescription Patterns of Antidepressants in Asia.

PURPOSE: Little is known regarding the trend of polypharmacy in Asia. We used data from 5 Asian countries to examine the patterns of antidepressant (AD) prescription and trends of psychotropic polypharmacy over time. METHODS: We used the cross-sectional, pharmacoepidemiological data from 2004 and 2013 REAP-AD (Research on Asian Psychotropic Prescription Patterns for Antidepressants) to examine the patterns of AD prescriptions in clinical settings in China, Japan, Korea, Singapore, and Taiwan. We compared the trend in polypharmacy (ie, concomitant use of ≥2 classes of psychotropic) among individuals receiving AD prescriptions in 2004 and 2013 using multivariable logistic regression models in different diagnostic categories. RESULTS: The proportion of patients with psychotropic polypharmacy decreased from 2004 to 2013 in all 3 diagnostic categories, including mood disorders (adjusted odds ratio [aOR], 0.44 [0.35-0.56]; P < 0.001), anxiety disorders (aOR, 0.58 [0.36-0.94]; P = 0.028), and psychotic disorders (aOR, 0.18 [0.05-0.60]; P = 0.006). Among individuals with AD prescriptions, concomitant use of anxiolytics (including sedative-hypnotics) decreased in patients with mood disorders (aOR, 0.34 [0.27-0.42]; P < 0.001) and anxiety disorders (aOR, 0.43 [0.27-0.67]; P < 0.001). In contrast, concomitant use of antipsychotics in patients with mood disorders increased (aOR, 1.43 [1.15-1.77]; P = 0.001), and concomitant use of mood stabilizers in patients with psychotic disorders also increased (aOR, 3.49 [1.50-8.14]; P = 0.004). CONCLUSIONS: This is the first study examining trends in psychotropic polypharmacy in East Asia. We found a generally decreasing trend of psychotropic polypharmacy in contrast to the increasing trend reported from Western countries. These findings could offer significant implications for health system reform or policy making.

Trends in the Misuse of Tranquilizers, Sedatives, and Sleeping Pills by Adolescents in Spain, 2004-2014.

PURPOSE: Misuse of prescription medication has increased during the last 20 years among adolescents and young adults. We aimed to report the prevalence and factors associated with misuse of tranquilizers, sedatives, and sleeping pills (TSSp) in high-school students in Spain. We also analyzed misuse of these drugs during the decade 2004-2014. METHODS: Nationwide, epidemiological, cross-sectional study on the misuse of TSSp by the Spanish school population. We used individualized secondary data retrieved from the 2004 and 2014 Spanish State Survey on Drug Use in Secondary Education. A total of 179,114 surveys respondents aged 14-18 years. Estimates and trends of previous 30 days misuse of TSSp. RESULTS: The prevalence of TSSp misuse among school population aged 14-18-years increased significantly from 2004 (2.40%) to 2014 (2.96%). The values for consumption were always greater in adolescent girls than boys throughout the study (3.51% vs. 2.18%). The variables associated with a greater probability of TSSp misuse were consumption of alcohol, tobacco, and marijuana. Students who reported consumption of an illicit drug other than marijuana during the previous year are 4.91 times more likely to misuse TSSp (adjusted odds ratio = 4.91; 95% confidence interval, 4.15-5.81). CONCLUSIONS: We found that misuse of TSSp by adolescents in Spain has significantly increased from 2004 to 2014. Misuse of TSSp was more likely in adolescent girls than Spanish boys. Alcohol, tobacco, and marijuana consumption are factors associated with the use of TSSp.

Leisure time physical activity and incident use of prescription tranquilizers: A longitudinal population-based study.

OBJECTIVE: Physical inactivity is a major public health problem associated with an increased risk of several psychiatric and physical conditions. This study investigated the association between leisure time physical activity (PA) and incident use of prescription tranquilizers in a regionally representative and prospective cohort. METHODS: A total of 4043 men and women (mean age: 61.3 years; 57% women) from the Tromsø Study were followed for six years. Leisure time PA was captured at baseline. Psychiatric morbidity was measured by use of prescription tranquilizers, captured at both baseline and follow-up. Leisure time PA at baseline was used as a predictor of subsequent (incident) use of prescription tranquilizers. We used multinomial regression models and Poisson regression models to estimate relative risk-ratios (RRRs), and relative risks (RRs), respectively, and their corresponding 95% confidence intervals (CIs). RESULTS: In the fully-adjusted model, accounting for socio-demographic factors, parental history of psychopathology, years of education, smoking, respondent's psychopathology at baseline, and occupational PA, a lower leisure time PA conferred a 41% increased risk of incident use of prescription tranquilizers at follow-up (RR = 1.41, 95% CI: 1.09, 1.83; p = 0.010). CONCLUSIONS: These findings suggest that physical inactivity increases the risk of psychiatric morbidity (albeit, measured via use of prescription tranquilizers). Future regionally representative and longitudinal research is required to confirm/refute our findings and explore underlying mechanisms.

The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium.

BACKGROUND: The Richmond Agitation-Sedation Scale (RASS) is commonly used to assess psychomotor activity; however, to the authors' knowledge, its minimal clinically important difference (MCID) has not been determined to date. The objective of the current study was to identify the MCID for RASS using 2 anchor-based approaches. METHODS: The current study was a secondary analysis of a randomized controlled trial to compare the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium. The primary outcome was change in RASS (10-point numeric rating scale ranging from -5 [unarousable] to +4 [combative]) from baseline to 8 hours after treatment administration. The sensitivity-specificity and within-patient change methods were used to identify the MCID, with the anchor being patient comfort after the study intervention as perceived by caregivers and nurses. RESULTS: A total of 90 patients were randomized and 58 (64%) received the study medication for restlessness/agitation (mean baseline RASS, 1.6). A total of 23 caregivers (61%) and 23 nurses (55%) perceived that the patient was more comfortable after treatment. Using the sensitivity-specificity method, the optimal RASS reduction was ≥4 points according to both caregivers (sensitivity of 61% and specificity of 80%; area under the curve, 0.71) and nurses (sensitivity of 73% and specificity of 84%; area under the curve, 0.78). The RASS cutoff value based on the within-patient change method was similar (-4.2 for caregivers and -4.0 for nurses). CONCLUSIONS: For patients with persistent restlessness/agitation, a reduction of ≥4 points in RASS was considered to be the MCID for both nurses and caregivers. These preliminary findings may have implications for sample size calculation and the interpretation of treatment effect in future delirium trials. Cancer 2018;124:2246-52. © 2018 American Cancer Society.