Hypnotic prescription trends and patterns for the treatment of insomnia in Japan: analysis of a nationwide Japanese claims database.

BACKGROUND: There is limited consensus regarding the optimal treatment of insomnia. The recent introduction of orexin receptor antagonists (ORA) has increased the available treatment options. However, the prescribing patterns of hypnotics in Japan have not been comprehensively assessed. We performed analyses of a claims database to investigate the real-world use of hypnotics for treating insomnia in Japan. METHODS: Data were retrieved for outpatients (aged ≥ 20 to < 75 years old) prescribed ≥ 1 hypnotic for a diagnosis of insomnia between April 1st, 2009 and March 31st, 2020, with ≥ 12 months of continuous enrolment in the JMDC Claims Database. Patients were classified as new or long-term users of hypnotics. Long-term use was defined as prescription of the same mechanism of action (MOA) for ≥ 180 days. We analyzed the trends (2010-2019) and patterns (2018-2019) in hypnotics prescriptions. RESULTS: We analyzed data for 130,177 new and 91,215 long-term users (2010-2019). Most new users were prescribed one MOA per year (97.1%-97.9%). In 2010, GABAA-receptor agonists (benzodiazepines [BZD] or z-drugs) were prescribed to 94.0% of new users. Prescriptions for BZD declined from 54.8% of patients in 2010 to 30.5% in 2019, whereas z-drug prescriptions remained stable (~ 40%). Prescriptions for melatonin receptor agonist increased slightly (3.2% to 6.3%). Prescriptions for ORA increased over this time from 0% to 20.2%. Prescriptions for BZD alone among long-term users decreased steadily from 68.3% in 2010 to 49.7% in 2019. Prescriptions for ORA were lower among long-term users (0% in 2010, 4.3% in 2019) relative to new users. Using data from 2018-2019, multiple (≥ 2) MOAs were prescribed to a higher proportion of long-term (18.2%) than new (2.8%) users. The distribution of MOAs according to psychiatric comorbidities, segmented by age or sex, revealed higher proportions of BZD prescriptions in elderly (new and long-term users) and male (new users) patients in all comorbidity segments. CONCLUSION: Prescriptions for hypnotics among new and long-term users in Japan showed distinct patterns and trends. Further understanding of the treatment options for insomnia with accumulating evidence for the risk-benefit balance might be beneficial for physicians prescribing hypnotics in real-world settings.

Prevalência e fatores associados ao uso de medicamento indutor do sono entre mulheres assistidas na Atenção Primária à Saúde: estudo transversal em Vitória, Espírito Santo, 2014 / Prevalencia y factores asociados al uso de medicamentos inductores del sueño en mujeres atendidas en Atención Primaria de Salud: estudio transversal en Vitória, Espírito Santo, Brasil, 2014 / Prevalence and factors associated with the use of sleep-inducing medication among women receiving Primary Health Care: a cross-sectional study in Vitória, Espírito Santo, Brazil, 2014

Objetivo: Verificar a prevalência e fatores associados ao uso de medicamento indutor do sono entre mulheres assistidas na Atenção Primária à Saúde (APS), Vitória, ES, Brasil. Métodos: Estudo transversal com mulheres de 20-59 anos, realizado em 2014. Analisou-se a associação do uso de indutor do sono com fatores socioeconômicos e experiências de violência (regressão de Poisson). Resultados: Entre 991 participantes, 18,5% usavam medicamento indutor do sono e 45,9% usaram-no alguma vez na vida. Seu uso, atualmente e ao longo da vida, associou-se a idade, escolaridade e violências psicológica, física e sexual no último ano (p-valor<0,05). Menor renda familiar (RP=1,30; IC95% 1,03;1,64) e parceiro controlador (RP=1,35; IC95% 1,08;1,69) associaram-se ao uso atual, enquanto experiência de violência sexual na infância (RP=1,33; IC95% 1,13;1,56) associou-se ao uso alguma vez na vida. Conclusão: O uso de medicamento indutor do sono foi frequente entre usuárias da APS, associando-se a fatores socioeconômicos e experiências de violência.

Objetivo: Verificar la prevalencia y los factores asociados al uso de medicamentos inductores del sueño en mujeres en la Atención Primaria de Salud (APS) de Vitória, ES, Brasil. Métodos: Estudio transversal con mujeres de 20 a 59 años realizado en 2014. Se analizó la asociación del uso de inductores del sueño con factores socioeconómicos y violencia (regresión de Poisson). Resultados: Entre las 991 participantes, 18,5% usó medicamentos inductores y 45,9% los había usado en algún momento. El uso, actual y en la vida, de estos medicamentos se asoció con la edad, años de educación, violencia psicológica, física y sexual en el último año (p-valor<0,05). Ingresos familiares bajos (RP=1,30; IC95% 1,03;1,64) y pareja controladora (RP=1,35; IC95% 1,08;1,69) se asociaron con el uso actual, mientras que la experiencia de violencia en la infancia (RP=1,33; IC95% 1,13;1,56) se asoció con el uso alguna vez en la vida. Conclusión: El uso de inductores del sueño fue frecuente entre usuarias de la APS, asociado a factores socioeconómicos y violencia.

Objective: To verify prevalence and factors associated with the use of sleep-inducing medication among women receiving primary health care (PHC) in Vitória, ES, Brazil. Methods: This was a cross-sectional study conducted in 2014 with women aged 20-59. We analyzed association of sleep-inducing medication use with socioeconomic factors and experiences of violence (Poisson regression). Results: Out of 991 participants, 18.5% were using sleep-inducing medication and 45.9% had used it at some point in their lives. Current and lifetime use of these medications was associated with age, years of education, as well as psychological, physical and sexual violence in the last year (p-valor<0,05). Lower family income (PR=1.30; 95%CI 1.03;1.64) and controlling partner (PR=1.35; 95%CI 1.08;1.69) were associated with current use, while experience of sexual violence in childhood (PR=1.33; 95%CI 1.13;1.56) was associated with lifetime use. Conclusion: Use of sleep-inducing medication was frequent among PHC service users, and was associated with socioeconomic factors and experiences of violence.

Prevalence and factors associated with use of sleeping pills among older adults in Brazil.

OBJECTIVES: Little is known about sleeping pills consumption among older adults in low- and middle-income countries. This study investigated the prevalence and factors associated with sleeping pills use among Brazilians aged 50 and over. METHODS: A cross-sectional study was conducted using baseline data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a nationally representative study of persons aged 50 years and older (n = 9412). Univariate and bivariate analyses were used to describe the sample. Robust Poisson regression was employed to estimate prevalence ratios and predict probabilities. KEY FINDINGS: Prevalence of sleeping pills use among older Brazilians was estimated at 16.8%, with considerable disparities related to gender (22.3% among women and 10.3% among men), race/skin colour (19.7% among whites and 11.9% among blacks) and geographic region (ranging from 5.9% in the North to 20.5% in the South). The multivariate analysis showed associations between sleeping pills consumption and sociodemographic factors (age, gender, race/skin colour, geographic region and income), health status/behaviour characteristics (poor self-rated health status, number of chronic conditions and alcohol consumption) and variables related to healthcare utilisation (number of visits, usual source of care, care coordination, doctor's awareness of all medication, difficulty in managing own medication and number of medicines). CONCLUSIONS: Our work found that sleeping pills consumption is disproportionately prevalent among women, is associated with worse health status and increases with more medical office visits and use of additional medicines. Moreover, the large inexplicable variations in care deserve special attention from policy-makers and clinicians.

Prevalence and drug use correlates of extra-medical use of prescription medications for sleep among adults in the United States: Results of the 2015-2018 National Survey on Drug Use and Health.

BACKGROUND: This paper examines the epidemiology of extra-medical use of prescription medications for sleep among a nationally representative sample of U.S. adults. METHODS: We analyzed data from the 2015-2018 National Surveys on Drug Use and Health. The sample includes 3410 U.S. adults who reported extra-medical use of prescription medications for sleep. Multinomial logistic regression models identified correlates of type of drug used [i.e., sedatives and/or tranquilizers-only (ST-only), prescription pain relievers-only (PPR-only), or sedatives, tranquilizers, and prescription pain relievers (ST + PPR)], and logistic regression models identified correlates of reasons for extra-medical use (i.e., sleep-only vs. sleep and recreational). RESULTS: About 60% (95%CI = 58.9, 63.5) of the sample reported extra-medical use of ST-only, followed by PPR-only (29.9%, 95%CI = 27.5, 32.5), and ST + PPR (8.9%, 95%CI = 7.7, 10.4). Recreational use was reported by 28.4% (95% CI = 26.5, 30.4) of the sample. The odds of extra-medical use of PPR-only (aRRR = 3.1, 95%CI = 2.1, 4.5) and ST + PPR (aRRR = 1.9, 95%CI = 1.2, 3.1) as opposed to ST-only, were greater among Non-Hispanic Blacks than Non-Hispanic Whites. Compared to non-alcohol users, those with a past-12 months diagnosis of alcohol use disorder were more likely to use ST + PPR rather than ST-only (aIRR = 2.0, 95%CI = 1.1, 3.7). Non-Hispanic Blacks (aOR = 0.6, 95%CI = 0.4, 08) and individuals living in rural areas (aOR = 0.5, 95%CI = 0.3, 09) were less likely to report extra-medical use of prescription medications for recreational reasons than Non-Hispanic Whites and those residing in large metropolitan areas, respectively. CONCLUSIONS: Extra-medical use of PPR-only and ST + PPR as an aid to sleep, is prevalent among Non-Hispanic Blacks, young adults, and those residing in rural areas. Most individuals reported that extra-medical use of prescription medications was primarily motivated by sleep reasons, rather than by sleep and recreational reasons. Potential interventions include access to sleep treatments, education on the effectiveness and risk associated with extra-medical use and co-use of prescription medications for sleep, and research on sleep-related disparities.

Zolpidem Versus Trazodone Initiation and the Risk of Fall-Related Fractures among Individuals Receiving Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Zolpidem, a nonbenzodiazepine hypnotic, and trazodone, a sedating antidepressant, are the most common medications used to treat insomnia in the United States. Both drugs have side effect profiles (e.g., drowsiness, dizziness, and cognitive and motor impairment) that can heighten the risk of falls and fractures. Despite widespread zolpidem and trazodone use, little is known about the comparative safety of these medications in patients receiving hemodialysis, a vulnerable population with an exceedingly high fracture rate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the United States Renal Data System registry (2013-2016), we conducted a retrospective cohort study to investigate the association between the initiation of zolpidem versus trazodone therapy and the 30-day risk of hospitalized fall-related fractures among Medicare-enrolled patients receiving maintenance hemodialysis. We used an active comparator new-user design and estimated 30-day inverse probability of treatment-weighted hazard ratios and risk differences. We treated death as a competing event. RESULTS: A total of 31,055 patients were included: 18,941 zolpidem initiators (61%) and 12,114 trazodone initiators (39%). During the 30-day follow-up period, 101 fall-related fractures occurred. Zolpidem versus trazodone initiation was associated with a higher risk of hospitalized fall-related fracture (weighted hazard ratio, 1.71; 95% confidence interval, 1.11 to 2.63; weighted risk difference, 0.17%; 95% confidence interval, 0.07% to 0.29%). This association was more pronounced among individuals prescribed higher zolpidem doses (hazard ratio, 1.85; 95% confidence interval, 1.10 to 3.01; and risk difference, 0.20%; 95% confidence interval, 0.04% to 0.38% for higher-dose zolpidem versus trazodone; and hazard ratio, 1.60; 95% confidence interval, 1.01 to 2.55 and risk difference, 0.14%; 95% confidence interval, 0.03% to 0.27% for lower-dose zolpidem versus trazodone). Sensitivity analyses using longer follow-up durations yielded similar results. CONCLUSIONS: Among individuals receiving maintenance hemodialysis, zolpidem initiators had a higher risk of hospitalized fall-related fracture compared with trazodone initiators. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_12_18_CJN10070620_final.mp3.

Attitudes and thoughts of medical practitioners towards their profession in the era of financial crisis in Greece.

INTRODUCTION: The financial crisis which started in Greece about 10 years ago has affected the income of citizens, their quality of life, as well as social and occupational relationships. Aim of the present study was to assess the attitudes towards working conditions and personal life and to explore quality of life, as well as disorders in physical condition, sleep, mood and their predictors, among doctors working or being trained in a tertiary hospital of NE Greece. METHODS: Included were 133 medical students and doctors of all ranks (61.7% males) practicing medicine in a university tertiary hospital in Greece. All of them answered a 31-item questionnaire regarding their working conditions, and personal life, daytime activities and sleeping habits. RESULTS: In general, the majority reported dissatisfaction with the work environment, the salary and they rated their quality of life worse than that of the general population. Weekly workload exceeded 60 hours for the majority. No difference between sexes was revealed, with the exception of use of energy drinks which was more prevalent in males (70.7% vs. 51%, p = 0.022). Comparison between ranks revealed that medical students performed better in everyday activities and socialization, although prevalence of reported fatigue was higher in them. Finally, it was demonstrated that surgeons used more frequently medication to achieve sleep promotion (80.4% vs. 36%, p < 0.001) and daily energy (78.4% vs. 44%, p < 0.001). CONCLUSIONS: An overall dissatisfaction regarding workload, salary and quality of life is recorded among doctors of a tertiary hospital in Greece, with different coping strategies among subgroups.

Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial.

INTRODUCTION: We evaluated the clinical profile of the orexin receptor antagonist suvorexant for treating insomnia in patients with mild-to-moderate probable Alzheimer's disease (AD) dementia. METHODS: Randomized, double-blind, 4-week trial of suvorexant 10 mg (could be increased to 20 mg based on clinical response) or placebo in patients who met clinical diagnostic criteria for both probable AD dementia and insomnia. Sleep was assessed by overnight polysomnography in a sleep laboratory. The primary endpoint was change-from-baseline in polysomnography-derived total sleep time (TST) at week 4. RESULTS: Of 285 participants randomized (suvorexant, N = 142; placebo, N = 143), 277 (97%) completed the trial (suvorexant, N = 136; placebo, N = 141). At week 4, the model-based least squares mean improvement-from-baseline in TST was 73 minutes for suvorexant and 45 minutes for placebo; (difference = 28 minutes [95% confidence interval 11-45], p < 0.01). Somnolence was reported in 4.2% of suvorexant-treated patients and 1.4% of placebo-treated patients. DISCUSSION: Suvorexant improved TST in patients with probable AD dementia and insomnia.

Consequences of the new zolpidem prescription regulations: a cohort study from the French national healthcare database.

PURPOSE: To determine changes in the prevalence of zolpidem consumption since the change in the regulations of prescription. Formulations containing zolpidem were subject to the regulations of narcotics by the French decree of April 7, 2017. METHODS: Longitudinal cohort study using data from the representative French healthcare database. The main outcome was the prevalence of oral hypnotic drug reimbursement before and after April 2017. The secondary outcome was the change in prescription habits for zolpidem since the decree in long-term users and excessive users. RESULTS: A total of 81,174 individuals had at least one hypnotic drug reimbursement; among, whom 2143 had at least one reimbursement of zolpidem. Before the decree, 26% had at least one reimbursement of zolpidem, whereas it dropped to 18.4% after the decree. Among the 545 long-term users, the reimbursement of zolpidem was discontinued after the decree for 60.4% and 24.2% retained zolpidem as a treatment. The main replacement drug was zopiclone for 6.4% of them. Among the 1598 excessive users, the reimbursement of zolpidem was stopped after the decree for 16.5% and 56.3% retained zolpidem as a treatment. The main replacement drug was zopiclone for 12.1% of them. CONCLUSIONS: The French decree had a major impact on the reimbursement of oral zolpidem. Indeed, prescription of the hypnotic was discontinued for half of the long-term users of zolpidem, and just over one-sixth of the excessive users discontinued the prescription of zolpidem after the decree.

Positional Awake Endoscopy Versus DISE in Assessment of OSA: A Comparative Study.

OBJECTIVE: To compare awake endoscopy with Müller's maneuver (MM) during both sitting and supine positions, with drug-induced sleep endoscopy (DISE) as regard determination of different levels, patterns, and degrees of collapse of the upper airway in adult patients with obstructive sleep apnea (OSA). METHODS: The study included adult patients with OSA symptoms, who had apnea hypopnea index (AHI) > 15. Patients were examined by MM in a sitting position, then during supine position; DISE then followed. Site, pattern, and degree of obstruction were assessed by experienced examiners according to the nose oropharynx hypopharynx and larynx classification. RESULTS: Eighty-one adult subjects were included. The most common pattern of collapse at the retro-palatal level was the concentric pattern, while the predominant pattern at the hypopharyngeal level was the lateral wall collapse. The analysis of the pattern of collapse of the study group revealed that the individual pattern did not change (for the same patient at the same level) in the majority of patients whatever the maneuver or the position. CONCLUSION: This study demonstrates the feasibility of positional awake endoscopy for providing valuable surgical information as regard level, pattern, and degree of severity in OSA. The data of positional awake endoscopy were comparable to those gained from DISE with less morbidity and costs. The idea and results of this work provide a useful foundation for future research in this area. Multicenter studies are encouraged to obtain more reliable conclusions and more clear standards aiming at a better surgical planning. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2269-2274, 2020.

Using recreational cannabis to treat insomnia: Evidence from over-the-counter sleep aid sales in Colorado.

This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store scanner data in a multivariable panel regression design were used to compare the change in the monthly market share of sleep aids with varying dispensary-based recreational cannabis access (existence, sales, and count) in Colorado counties between 12/2013 and 12/2014. We measured annually-differenced market shares for sleep aids as a portion of the overall OTC medication market, thus accounting for store-level demand shifts in OTC medication markets and seasonality, and used the monthly changes in stores' sleep aid market share to control for short-term trends. Relative to the overall OTC medication market, sleep aid market shares were growing prior to recreational cannabis availability. The trend reverses (a 236% decrease) with dispensary entry (-0.33 percentage points, 95% CI -0.43 to -0.24, p < 0.01) from a mean market share growth of 0.14 ±â€¯0.97. The magnitude of the market share decline increases as more dispensaries enter a county and with higher county-level cannabis sales. The negative associations are driven by diphenhydramine- and doxylamine-based sleep aids rather than herbal sleep aids and melatonin. These findings support survey evidence that many individuals use cannabis to treat insomnia, although sleep disturbances are not a specific qualifying condition under any U.S. state-level medical cannabis law. Investigations designed to measure the relative effectiveness and side effect profiles of conventional OTC sleep aids and cannabis-based products are urgently needed to improve treatment of sleep disturbances while minimizing potentially serious negative side effects.

Over-indebtedness and its association with sleep and sleep medication use.

BACKGROUND: Over-indebtedness is currently rising in high-income countries. Millions of citizens are confronted with the persistent situation when household income and assets are insufficient to cover payment obligations and living expenses. Previous research shows that over-indebtedness increases the risk of various adverse health effects. However, its association with sleep problems has not yet been examined. The objective of this study was to investigate the association between over-indebtedness and sleep problems and sleep medication use. METHODS: A cross-sectional study on over-indebtedness (OID survey) was conducted in 70 debt advisory centres in Germany in 2017 that included 699 over-indebted respondents. The survey data were combined with the nationally representative German Health Interview and Examination Survey for Adults (DEGS1; n = 7987). We limited analyses to participants with complete data on all sleep variables (OID: n = 538, DEGS1: n = 7447). Descriptive analyses and logistic regression analyses were used to examine the association between over-indebtedness and difficulty initiating and maintaining sleep, and sleep medication use. RESULTS: A higher prevalence of sleep problems and sleep medication use was observed among over-indebted individuals compared to the general population. After adjustment for socio-economic and health factors (age, sex, education, marital status, employment status, subjective health status and mental illness), over-indebtedness significantly increased the risk of difficulties with sleep onset (adjusted odds ratio (aOR) 1.79, 95%-confidence interval (CI) 1.45-2.21), sleep maintenance (aOR 1.45, 95%-CI 1.17-1.80) and sleep medication use (aOR 3.94, 95%-CI 2.96-5.24). CONCLUSIONS: Evidence suggests a strong association between over-indebtedness and poor sleep and sleep medication use independent of conventional socioeconomic measures. Considering over-indebtedness in both research and health care practice will help to advance the understanding of sleep disparities, and facilitate interventions for those at risk. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00013100 (OID survey, ArSemü); Date of registration: 23.10.2017; Date of enrolment of the first participant: 18.07.2017, retrospectively registered.

French national health insurance database analysis and field study focusing on the impact of secure prescription pads on zolpidem consumption and sedative drug misuse: ZORRO study protocol.

INTRODUCTION: In recent years, data collected by the French Addictovigilance Network have shown the potential for abuse and addiction associated with zolpidem (the most sold hypnotic drug in France). Since 10 April 2017, new regulations have come into force that require zolpidem to be prescribed on special secure prescription pads, in order to reduce the risk of abuse or misuse. This measure has far-reaching repercussions that are not only limited to the consumption of zolpidem but also extend to the usage of sedative medication on a whole. The objective of the ZOlpidem and the Reinforcement of the Regulation of prescription Orders (ZORRO) study is to evaluate the overall impact of the new regulatory framework requiring zolpidem to be prescribed on special secure prescription pads. Three axes will be evaluated: the number of consumers, the type of consumption (chronic use versus occasional use, problematic consumption versus non-problematic use) and the consumption of other sedative molecules.The study has been registered in the Protocol Registration and Results System under the number NCT03584542 at stage "Pre-results". METHODS AND ANALYSIS: The ZORRO study is an epidemiological, observational, national multicentre, non-controlled, prospective research project supported by the French National Agency for Medicines and Health Products Safety. The evaluation of the impact of the regulatory framework change relative to zolpidem will be done according to two axes: via an epidemiological study of the French National Health Insurance database and by the implementation of field studies of prescribers and consumers of zolpidem. ETHICS AND DISSEMINATION: The Nantes Research Ethics Committee (Groupe Nantais d'Ethique dans le Domaine de la Santé), the Committee for the Protection of the Population and the Committee of Expertise in Research, Studies and Evaluations in the Field of Health approved this study. Results will be presented in national and international conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03584542; Pre-results.

Assessment and comparison of sleep patterns among medical and non-medical undergraduates of Karachi: A cross-sectional study - SPECIAL REPORT.

To assess and compare patterns, habits and quality of sleep in undergraduate medical and non-medical students. The cross-sectional study was conducted from February to March, 2018, at Dow Medical College, Karachi, and Pakistan Air Force-Karachi Institute of Economics and Technology. Data was collected by self-reported questionnaires. Sleep quality of individuals was assessed using Pittsburg Sleep Quality Index. Data was analysed using SPSS 21. Of the 245 subjects, 137(55%) were medical students and 108(45%) were non-medical. Overall, 101(41.2%) subjects aid 8 hours of sleep was sufficient for them; 153(62.4%) reported daytime sleeping; and 168(68.5%) did not take naps. The duration of nap was >30 minutes in 118(48%) students. Factors affecting sleep were cited as electronic media 132(53.9%), caffeine 42(17.1%) and stress 126(51.4%). Of the total, 161(65.7%) subjects had poor sleep quality. There was no significant difference between medical and non-medical students (p>0.05). Majority of medical and non-medical undergraduate students were poor sleepers.

An Assessment of Sleep Disturbance in Patients before and after Carpal Tunnel Release.

Background: Night time numbness is a key characteristic of CTS and relief of night time symptoms is one of the outcomes most important to patients. This study tested the null hypothesis that there is no difference between sleep quality and night symptoms before and after carpal tunnel release (CTR). Methods: Forty-four, English-speaking adult patients requesting open CTR for electrodiagnostically confirmed carpal tunnel syndrome completed questionnaires before and after surgery. Average age was 59, 24 patients were men and 20 were women. Patient with a primary or secondary sleep disorder were excluded. Before surgery, patients completed the Pittsburg Sleep Quality index (PSQI). At an average of 3 months after surgery, participants completed PSQI questionnaires. Onset of sleep quality improvement was specifically addressed. Differences between preoperative and postoperative sleep quality were evaluated using the paired t-test. Spearman correlations were used to assess the relationship between continuous variables. Results: Of the 44 patients, 32 (72%) were classified as poor sleepers (PSQI > 5.5) prior to surgery. At 3 months follow up, there was a significant improvement PSQI global scores (7.8 ± 5.1 vs 4 ± 3.5, p < 0.001) as well as subdivisions. Daytime dysfunction (0.2 ± 0.4, p < 0.001) and medication use (1.0 ± 1.2 vs 0.9 ± 1.2, p < 0.045) secondary to sleep disturbance and was improved as well. In all patients, onset of improvement was within 24 hours of surgery. Conclusions: CTR is associated with improvement in sleep quality at 3 months follow-up. CTR improves daytime dysfunction related to the sleep disturbance. The onset of sleep improvement is 24 hours after surgery in most cases.

Trends in prescriptions for sedative-hypnotics among Korean adults: a nationwide prescription database study for 2011-2015.

PURPOSE: This study investigated prescriptions for sedative-hypnotics via data obtained from the Health Insurance Review and Assessment (HIRA) service. METHODS: Data on sedative-hypnotic prescriptions from the HIRA service of the Republic of Korea were analyzed from 2011 to 2015. We included prescriptions for subjects > 18 years of age from hospitals and community healthcare centers. In addition, subgroup analyses with a subsample restricted to prescriptions from patients with diagnostic codes F510 (nonorganic insomnia) or G470 (insomnia) were performed. After analyzing the number of prescriptions by individual pharmacy items, the prescription codes were grouped as: (1) benzodiazepines; (2) non-benzodiazepines, including zolpidem; (3) antidepressants; and (4) antipsychotics. We calculated the monthly percent change in the number of prescriptions by drug group using Joinpoint regression. RESULTS: Among the sedative-hypnotic groups, benzodiazepines were the most commonly prescribed drugs in Korea during the study period. As a single sedative-hypnotic item, zolpidem was the most frequently prescribed medication for patients with insomnia. Prescriptions for all groups of sedative-hypnotics increased significantly during the study period. When stratified by age group, antipsychotic prescriptions increased significantly by 0.19-0.21% per month among men and women aged 50-59 years and > 70 years. Prescriptions for antidepressants in 30-39-year-old men increased significantly by 0.20%. CONCLUSIONS: Benzodiazepine prescriptions as well as those for antipsychotics and antidepressants to treat insomnia increased during 2011-2015 in Korea. Monitoring the use of sedative-hypnotics at the national level is necessary, especially in the elderly population.

Preclinical assessment of the abuse potential of the orexin receptor antagonist, suvorexant.

Suvorexant (Belsomra®) is a dual orexin receptor antagonist approved for the treatment of insomnia. Because of its pharmacology within the central nervous system, intended therapeutic indication, and first-in-class status, an assessment of suvorexant abuse liability potential was required prior to marketing approval. The nonclinical abuse liability potential studies for suvorexant included: 1) rat drug-dependence model to assess physical dependence following abrupt cessation; 2) rat drug-discrimination model to examine the potential similarity of the interoceptive or subjective effects of suvorexant to those elicited by zolpidem and morphine; 3) self-administration model to assess the relative reinforcing efficacy of suvorexant in rhesus monkeys conditioned to self-administer methohexital. No significant signs of spontaneous drug withdrawal or 'discontinuation syndrome' were observed in rats following abrupt discontinuation of suvorexant. Suvorexant did not elicit complete cross-generalization to either a zolpidem or morphine training/reference stimuli in rats, and suvorexant was devoid of behavioral evidence of positive reinforcing efficacy in monkeys. These nonclinical findings suggested that suvorexant will have low abuse potential in humans. In the final regulatory risk assessment, suvorexant was placed into Schedule IV, likely due to its first-in-class status, its sedative properties, and the outcome of the clinical abuse potential assessment.

Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): study protocol for a randomised controlled trial.

BACKGROUND: Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances, usually due to illness. It occurs commonly in the intensive care unit (ICU), and it is associated with greater morbidity and mortality. It is likely that disturbances of sleep and of the day-night cycle play a significant role. Melatonin is a naturally occurring, safe and cheap hormone that can be administered to improve sleep. The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults, when compared with placebo, decreases the rate of delirium. METHODS: This trial will be a multi-centre, randomised, placebo-controlled study conducted in closed ICUs in Australia. Our aim is to enrol 850 adult patients with an expected ICU length of stay (LOS) of 72 h or more. Eligible patients for whom there is consent will be randomised to receive melatonin 4 mg enterally or placebo in a 1:1 ratio according to a computer-generated randomisation list, stratified by site. The study drug will be indistinguishable from placebo. Patients, doctors, nurses, investigators and statisticians will be blinded. Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14 days after enrolment, whichever occurs first. Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score. Data will also be collected on demographics, the overall prevalence of delirium, duration and severity of delirium, sleep quality, participation in physiotherapy sessions, ICU and hospital LOS, morbidity and mortality, and healthcare costs. A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep. DISCUSSION: Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes. This trial will be the largest evaluation of melatonin as a prophylactic agent to prevent delirium in the critically ill population. This study will also provide one of the largest series of polysomnographic testing done in ICU. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) number: ACTRN12616000436471 . Registered on 20 December 2015.

Racial disparities in sleep: the role of neighborhood disadvantage.

OBJECTIVE: Disparities in sleep duration and efficiency between Black/African American (AA) and White/European American (EA) adults are well-documented. The objective of this study was to examine neighborhood disadvantage as an explanation for race differences in objectively measured sleep. METHODS: Data were from 133 AA and 293 EA adults who participated in the sleep assessment protocol of the Midlife in the United States (MIDUS) study (57% female; Mean Age = 56.8 years, SD = 11.4). Sleep minutes, onset latency, and waking after sleep onset (WASO) were assessed over seven nights using wrist actigraphy. Neighborhood characteristics were assessed by linking home addresses to tract-level socioeconomic data from the 2000 US Census. Multilevel models estimated associations between neighborhood disadvantage and sleep, and the degree to which neighborhood disadvantage mediated race differences in sleep controlling for family socioeconomic position and demographic variables. RESULTS: AAs had shorter sleep duration, greater onset latency, and higher WASO than EAs (ps < 0.001). Neighborhood disadvantage was significantly associated with WASO (B = 3.54, p = 0.028), but not sleep minutes (B = -2.21, p = 0.60) or latency (B = 1.55, p = 0.38). Furthermore, race was indirectly associated with WASO via neighborhood disadvantage (B = 4.63, p = 0.035), which explained 24% of the race difference. When measures of depression, health behaviors, and obesity were added to the model, the association between neighborhood disadvantage and WASO was attenuated by 11% but remained significant. CONCLUSION: Findings suggest that neighborhood disadvantage mediates a portion of race differences in WASO, an important indicator of sleep efficiency.