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Aim: The current study aimed to examine the effect of Japanese policies for appropriate hypnotics use and novel hypnotics (e.g. melatonin receptor agonist and orexin receptor antagonist [ORA]) on long‐term prescriptions of hypnotics. Methods: This retrospective study was conducted using a large‐scale health insurance claims database. Among subscribers prescribed hypnotics at least once between April 2005 and March 2021, those prescribed hypnotics for the first time after being included in the database in three periods (period 1: April 2012–March 2013; period 2: April 2016–March 2017; and period 3: April 2018–March 2019) were eligible. These were set considering the timing of the 2014 and 2018 medical fee revisions (2014 for polypharmacy of three or more hypnotics, 2018 for long‐term prescription of benzodiazepine receptor agonists for >12 months). The duration of consecutive prescriptions of hypnotics over 12 months was evaluated. Factors associated with short‐term prescriptions of hypnotics were also investigated. Results: In total, 186 535 participants were newly prescribed hypnotics. The mean duration of prescriptions was 2.9 months, and 9.3% of participants were prescribed hypnotics for 12 months. Prescription periods were not associated with short‐term prescriptions of hypnotics. ORA use was associated with short‐term prescriptions of hypnotics (adjusted hazard ratio, 1.077 [95% confidence interval, 1.035–1.120]; P < 0.001), but melatonin receptor agonist use was not. Conclusion: Japanese policies had no statistically significant effect on long‐term prescriptions of hypnotics. Although this study suggests initiating ORA for insomniacs as a candidate strategy to prevent long‐term prescriptions of hypnotics, further research is necessary to draw conclusions. [ABSTRACT FROM AUTHOR]

Abstract Background Some people can subconsciously wake up naturally (self-awakening) at a desired/planned time without external time stimuli. However, the underlying mechanism regulating this ability remains to be elucidated. This study sought to examine the relationship between hemodynamic changes in oxyhemoglobin (oxy-Hb) level in the prefrontal cortex and sleep structures during sleep in subjects instructed to self-awaken. Results Fifteen healthy right-handed male volunteers with regular sleep habits participated in a consecutive two-night crossover study. The subjects were instructed to wake up at a specified time (“request” condition) or instructed to sleep until the morning but forced to wake up at 03:00 without prior notice (“surprise” condition). Those who awoke within ± 30 min of the planned waking time were defined as those who succeeded in self-awakening (“success” group). Seven subjects succeeded in self-awakening and eight failed. No significant differences were observed in the amounts of sleep in each stage between conditions or between groups. On the “request” night, an increase in oxy-Hb level in the right prefrontal cortex and a decrease in δ power were observed in the “success” group around 30 min before self-awakening, whereas no such changes were observed in the “failure” group. On the “surprise” night, no significant changes were observed in oxy-Hb level or δ power in either group. Conclusions These findings demonstrate a correlation between self-awakening and a pre-awakening increase in hemodynamic activation in the right prefrontal cortex, suggesting the structure’s contribution to time estimation ability.

Aims: Benzodiazepine receptor agonists (BZ‐RAs) are frequently prescribed to treat insomnia; however, their long‐term use is not recommended. To introduce an appropriate pharmaco‐therapy, the current state and background factors of BZ‐RAs' dependence must be elucidated. In this study, we developed a Japanese version of the Benzodiazepine Dependence Self‐Report Questionnaire (Bendep‐SRQ‐J) and conducted a study of BZ‐RAs' use disorder. Methods: The Bendep‐SRQ‐J was created with permission from the original developer. Subjects were inpatients and outpatients receiving BZ‐RAs between 2012 and 2013. Clinical data collected were Bendep‐SRQ‐J scores, sleep disorders for which BZ‐RAs were prescribed, physical comorbidities, psychotropic drugs, and lifestyle factors. Logistic analysis was performed to extract factors associated with severe symptoms. Results: Of the 707 patients prescribed BZ‐RAs, 324 had voluntarily tapered or discontinued their drugs. Logistic analysis showed that the total number of drugs administered in the last 6 months correlated with both worsening of symptoms or conditions. This was more notable among younger patients, and the proportion of patients with severe symptoms or conditions increased with the increasing number of drugs. Conclusion: Using the Bendep‐SRQ‐J, we elucidated the current state of BZ‐RA dependence. Nearly half of the patients were non‐compliant. The proportion of patients with severe symptoms or disease conditions increased with the increase in the number of drugs administered. These findings highlight the need for clinicians to be aware of the likelihood of benzodiazepine dependence, especially in young patients and patients prescribed multiple hypnotics. [ABSTRACT FROM AUTHOR]

Background: Residual insomnia is associated with a risk of depression recurrence.Methods: In this retrospective, longitudinal cohort study, the recurrence pattern of depression in patients with or without residual insomnia was assessed using a health insurance claims database. Patients who were diagnosed with major depressive disorder and prescribed antidepressants, between January 2006 and June 2017 in Japan, were enrolled in the study. Residual insomnia was defined by a prescription of hypnotics, and recurrence of depression by prescription of antidepressants. Main outcomes included time to recurrence and the 1-year recurrence rate. Factors associated with recurrence of depression were assessed by multivariate analyses. The effect of residual insomnia on the frequency of recurrence was assessed by Chi-square test.Results: Of the 30,381 patients analyzed, there were 4,166 and 26,215 patients with or without residual insomnia, respectively. Time to recurrence in patients with residual insomnia was significantly shorter compared with those without residual insomnia (p <0.001), with a 1-year recurrence rate (95% CI) of 43.4% (41.9-45.0) and 7.4% (7.1-7.7), respectively. The frequency of recurrence was significantly higher in patients with residual insomnia than in those without (p <0.0001). A higher risk of depression recurrence (odds ratio 9.98, 95% CI 9.22-10.81) was found for residual insomnia compared with other significant factors.Limitations: The diagnosis stated in the receipt data may not accurately reflect the patient's condition, and medication adherence was unknown but assumed.Conclusions: Residual insomnia is a significant risk factor for depression recurrence in Japanese patients. [ABSTRACT FROM AUTHOR]

Patients with chronic insomnia are prone to long-term use of hypnotics. Reported risk factors include aging, female sex, and comorbid psychiatric disorders. However, most previous studies have been cross-sectional cohort studies. We conducted a retrospective cohort study using medical service payment data for 330,000 people to determine the duration of prescription of hypnotics and the risk factors for long-term use. We followed up 3981 patients (2382 M, 1599 F, age 40.3 ± 12.4 years) who were prescribed hypnotics for the first time between April 2005 and March 2008. Of these 3981 patients, 59.6% were prescribed hypnotics for only 1 month, 11.3% were prescribed hypnotics for 2 consecutive months, and 10.1% of patients continued receiving prescriptions for the entire 12-month observation period. In multiple logistic time-dependent Cox analyses, use of antidepressants, mean dose of hypnotics, and advanced age were significantly associated with long-term use of hypnotics (p < 0.01). In an analysis of the association between long-term use of hypnotics and prescribed dosage, high monthly dose, advanced age, and department of first visit were significantly associated with long-term use (p < 0.01). These clinical indicators may be effective for early identification of patients with insomnia who are at high risk of developing physical dependence on hypnotics. [ABSTRACT FROM AUTHOR]

Background Antihistamines with strong sedative-hypnotic properties are frequently prescribed for insomnia secondary to allergy, but the potential risks of such administration have not been fully elucidated. Subjects and methods This randomized, double-blind, placebo-controlled crossover study was conducted to evaluate next-day sleepiness and psychomotor performance following the administration of antihistamines. Twenty-two healthy male participants participated in four drug administration sessions with more than a 1-week interval between the sessions. Either zolpidem 10 mg, or diphenhydramine 50 mg, or ketotifen 1 mg, or a placebo was administered before sleep, and polysomnography was conducted to evaluate sleep. In the morning and afternoon of the day after administration, the participants were evaluated for subjective sleepiness, objective sleepiness, and psychomotor performance. Results The antihistamines with high blood-brain barrier-crossing efficiency were significantly associated with sleepiness and psychomotor performance decline the next day. Ketotifen showed the strongest carryover effect, followed by diphenhydramine. Compared with the placebo, no significant carryover effect was observed with zolpidem. Conclusion The results suggest that the risk-benefit balance should be considered in the ready use of antihistamines that easily cross the blood-brain barrier for alleviating secondary insomnia associated with allergies. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Although sleep disorders are highly prevalent among patients with physical disorders, only limited information is available about the actual status of sleep-related problems in inpatients of acute hospital wards. We conducted a multicenter cross-sectional observational survey investigating the prevalence of sleep disorders and use of hypnotic-sedative drugs among inpatients of acute wards in 44 general hospitals in Japan. Method: Questionnaire-, actigraph- and observation-based sleep evaluations were simultaneously performed in 557 adult inpatients [mean age 72.8±12.8 (S.D.) years] of acute wards during a one-month period in July 2007. Results: Of the 421 patients with data available, 22.3% had at least one of the following sleep disorders: sleep apnea syndrome, restless legs syndrome, periodic limb movement disorder and nocturnal behavior disorder. Similarly, 62.7% had insomnia, 6.9% had severe daytime sleepiness and 12.8% had other sleep-related symptoms. Only 13.8% were free of any sleep-related problem. Although 33.7% of insomnia patients were taking hypnotic-sedative drugs, 65.2% of them complained of residual insomnia symptoms. Conclusion: The findings obtained in this study have revealed the remarkably high prevalence of sleep-related problems experienced by inpatients of acute hospital wards in Japan. Proper diagnosis of sleep disorders should be made among patients with physical disorders. [Copyright &y& Elsevier]

Background: The aims of this study were 1) to clarify the prevalence of sleep problems (insomnia, insufficient sleep, and delayed sleep-wake phase) among Japanese university students; 2) to examine sociodemographic characteristics, lifestyle, and sleep-related symptoms in each sleep problem; and 3) to evaluate the association between the above-mentioned sleep problems and daytime dysfunction in school life.Methods: Self-report questionnaire surveys were conducted at eight universities in Japan, and we received 1034 valid answers (78% female). The questionnaire consisted of socio-demographic characteristics, information on lifestyle, sleep pattern, sleep-related symptoms, and daytime dysfunction in school life. Groups with insomnia, behaviorally induced insufficient sleep syndrome (BIISS), delayed sleep-wake phase (DSWP), and BIISS + DSWP were defined. To identify the association between sleep problems and daytime dysfunction in school life, the generalized linear mixed effect model was conducted.Results: Sleep duration on weekdays was 5.9 ± 1.2 h, and 38.2% of the students had a sleep duration < 6.0 h. About 16% of the students were categorized as evening-type individuals. More than half of the students (56.1%) had excessive daytime sleepiness. Insomnia was associated with tardiness (aOR: 0.8, 95%CI: 0.7-0.9) and falling asleep during class (aOR: 1.6: 95%CI: 1.4-2.0). BIISS was associated with tardiness (aOR: 1.5, 95%CI: 1.1-2.2) and interference with academic achievement (aOR: 1.9, 95%CI: 1.3-2.6). DSWP and BIISS + DSWP were associated with absence (aOR: 3.4, 95%CI: 2.2-5.1 / aOR: 4.2, 95%CI: 3.2-5.6), tardiness (aOR: 2.7, 95%CI: 1.8-4.1 / aOR: 2.2, 95%CI: 1.6-2.8), falling asleep during class (aOR: 2.6, 95%CI: 1.4-4.8 / aOR: 7.6, 95%CI: 3.3-17.2), and interference with academic achievement (aOR: 2.6, 95%CI: 1.7-3.9 / aOR: 2.1, 95%CI: 1.6-2.8).Conclusions: Students with DSWP and BIISS + DSWP were significantly associated with daytime dysfunction in school life, i.e. absence, tardiness, falling asleep during class and interference with academic achievement. Students displaying BIISS + DSWP were considered to have a relatively more serious condition compared with those with only insomnia, DSWP, or BIISS. It is therefore of utmost importance that university students aim to prevent DSWP and BIISS which were associated with daytime function in school life. [ABSTRACT FROM AUTHOR]

Abstract: Humans have the ability to estimate the passage of time in the absence of external time cues. In this study, we subjected 22 healthy males (aged 21.8±1.9 years) to a 40-min nap trial followed by 80min of wakefulness repeated over 28h, and investigated the relationship between various sleep parameters and the discrepancy (ΔST) of time estimation ability (TEA) during sleep, defined by the difference between actual sleep time (ST) and subjective sleep time (sub-ST) in each nap interval. Both ST and sub-ST were significant diurnal fluctuations with the peak in the early morning (9h after dim-light melatonin onset time, 2h after nadir time of core body temperature rhythm), and subjective sleep duration was estimated to be longer than actual times in all nap intervals (sub-ST>ST). There were significant diurnal fluctuations in discrepancy (sub-ST–ST) of TEA during sleep, and the degree of discrepancy correlated positively with increase in the amount of REM sleep and decrease in the amount of slow-wave sleep. These findings suggest that human TEA operates at a certain level of discrepancy during sleep, and that this discrepancy might be related to the biological clock and its associated sleep architecture. [ABSTRACT FROM AUTHOR]