Treatment strategies for insomnia in Japanese primary care physicians' practice: A Web-based questionnaire survey.

BACKGROUND: It is unclear how primary care physicians manage insomnia after the introduction of novel hypnotics such as orexin receptor antagonists and melatonin receptor agonists. This Web-based questionnaire survey aimed to examine treatment strategies for insomnia in Japanese primary care practice. METHODS: One-hundred-and-seventeen primary care physicians were surveyed on the familiarity of each management option for insomnia on a binary response scale (0 = "unfamiliar"; 1 = "familiar") and how they managed insomnia using a nine-point Likert scale (1 = "I never prescribe/perform it"; 9 = "I often prescribe/perform it"). Physicians who were unfamiliar with a management option were deemed to have never prescribed or performed it. RESULTS: Regarding medication, most physicians were familiar with novel hypnotics. Suvorexant was the most used hypnotic, followed by lemborexant and ramelteon. These novel hypnotics averaged 4.8-5.4 points and 4.0-4.7 points for sleep onset and sleep maintenance insomnia, respectively. By contrast, most benzodiazepines were seldom used below two points. Regarding psychotherapy, only approximately 40% of the physicians were familiar with cognitive behavioral therapy for insomnia (CBT-I) and they rarely implemented it, at an average of 1.5-1.6 points. More physicians were familiar with single-component psychotherapies (i.e., relaxation, sleep restriction therapy, and stimulus control) compared to CBT-I, and 48-74% of them implemented it slightly more often, with scores ranging from 2.6 to 3.4 points. CONCLUSION: This study suggests that Japanese primary care physicians seldom use CBT-I to treat insomnia. In addition, they use novel sleep medications more frequently than benzodiazepines in terms of pharmacotherapy. The use and availability of CBT-I in Japanese primary care might be facilitated by: educating primary care physicians, implementing brief or digital CBT-I, and/or developing collaborations between primary care physicians and CBT-I specialists.

Safety and Efficacy of Lemborexant in Insomnia Patients: Results of a Postmarketing Observational Study of Dayvigo® Tablets.

BACKGROUND AND OBJECTIVE: A prospective, postmarketing observational study was conducted to evaluate the safety and efficacy of lemborexant (LEM) tablets in daily clinical practice in Japan. No other studies of a similar size have been conducted since the marketing approval of LEM, making this the first report of its kind. METHODS: Insomnia patients (n = 550) administered LEM (5-10 mg daily) for the first time were enrolled. Adverse events were collected for target events (somnolence, parasomnia, narcolepsy and associated conditions, suicidal ideation and suicidal behavior). Overall improvement of insomnia symptoms was assessed by the investigator based on the patient's complaint. Subjective sleep onset latency (sSOL) and subjective total sleep time (sTST) were investigated as sleep parameters. RESULTS: A case report form was obtained from 539 patients. The incidence of adverse drug reactions (ADRs) was 7.65% for somnolence, 1.76% for nightmares, 0.59% for abnormal dreams, and 0.20% for sleep paralysis. No serious ADRs or ADRs related to suicidal ideation or suicidal behavior were observed. The efficacy rate at the final evaluation was 80.83%. Decreased sSOL and increased sTST were observed as assessed starting from Week 8 of treatment. CONCLUSION: Based on the results of this study, the safety result was consistent with the safety profile described in the current package insert. Efficacy results also indicated that LEM is clinically useful.

Association between sleep state misperception and bedtime behavior in patients with chronic insomnia.

Previous studies on sleep state misperception have objectively evaluated sleep status in special environments using polysomnography. There is a paucity of data from studies that evaluated habitual sleep status in home environments. The present study aimed to investigate sleep state misperception in the home environment of patients with chronic insomnia using a lumbar-worn actigraphy to identify sleep habits associated with sleep state misperception severity. Thirty-one patients and 42 healthy volunteers were included in the insomnia and non-insomnia group, respectively. Participants recorded subjective assessments in sleep diaries, objective assessments with an actigraphy worn for 14 days, and self-assessments using questionnaires. Both groups had similar objective sleep ratings; however, insomnia group had significantly worse subjective ratings (total sleep time, wake after sleep onset, and sleep onset latency). A significant correlation was found between subjective and objective total sleep time scores in non-insomnia group but not in insomnia group. Insomnia group had earlier bedtimes, significantly longer bedtimes, and impaired daytime functioning (Sheehan Disability Scale score); additionally, they underestimated their total sleep time, particularly with earlier bedtimes and longer laying durations. Monitoring the sleep status and habits of individuals in home environments could be instrumental in identifying key points for targeted interventions on sleep hygiene and cognitive behavioral therapy for insomnia.

Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder.

BACKGROUND: Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia. METHOD: Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression-Insomnia [PGI-I] questionnaire), and safety were also evaluated. RESULTS: In this subgroup of older adults (≥ 65 years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event. CONCLUSIONS: Improvements in subject-reported efficacy in LEM-treated adults age ≥ 65 years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016).

Insomnia is a common sleep disorder associated with significant difficulties, particularly in older adults. Although there are many drug treatments available, some are associated with the important risk of side effects and may not adequately treat sleep maintenance (ability to stay asleep), which is a frequent sleep complaint in older people. Lemborexant has been approved in multiple countries for the treatment of adults with insomnia based on studies that show lemborexant improved adults' ability to fall asleep and stay asleep and is well tolerated. To examine the long-term benefit of lemborexant, we investigated subject-reported benefits and safety of lemborexant in older (≥ 65 years) adults who participated in a 1-year study. The results showed that within the first few days of taking lemborexant, and lasting through 12 months of treatment, nightly lemborexant improved nighttime sleep (that is, it reduced the time it took to fall asleep, reduced the time awake during the night, and increased total sleep time) more than placebo. Morning alertness improved more in older adults who took lemborexant compared with placebo. In addition, those who took lemborexant also reported that their insomnia symptoms were less severe and they had less fatigue compared with placebo. Lemborexant was well tolerated in older adults. These results suggest that lemborexant may be a good option for older adults with insomnia disorder.

Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan.

Importance: Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. Objective: To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. Design, Setting, and Participants: This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. Exposures: Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. Main Outcomes and Measures: The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. Results: The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. Conclusions and Relevance: Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.

Impact of aripiprazole discontinuation in remitted major depressive disorder: a randomized placebo-controlled trial.

RATIONALE: The efficacy and safety of antidepressant augmentation therapy with aripiprazole (AATA) has been established; however, the ongoing effects of continuing aripiprazole after remission remain unclear because no studies have examined this issue. OBJECTIVES: We aimed to explore the effect of AATA discontinuation on the major depressive disorder (MDD) recurrence risk in patients with remitted MDD after AATA. METHODS: This 24-week, multicenter, placebo-controlled, double-blind, randomized trial evaluated recurrence risk in patients with MDD who achieved remission with AATA. Differences in MDD recurrence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, between the two groups were compared using survival analysis. The differences in depressive symptom severity and social functioning between the two groups were compared using a mixed model with repeated measures. Extrapyramidal symptoms and akathisia were also assessed. RESULTS: Twenty-three participants were randomized and treated. Two patients in each group experienced recurrence during the study. Kaplan-Meier analysis with Log-rank comparison showed no difference in recurrence between groups (p = 0.642). No significant difference in interactions between group and period was observed in the 17-item Hamilton depression rating scale (p = 0.492) or the Social and Occupational Functioning Assessment Scale (p = 0.638). No patients developed extrapyramidal symptoms or akathisia. CONCLUSIONS: Definitive conclusions could not be drawn owing to the small sample size. This study represents a starting point for investigating the safety of aripiprazole discontinuation on recurrence in patients with MDD who have achieved remission with AATA. Future studies with appropriate sample sizes calculated based on this study are needed.

Feasibility of a wrist-worn wearable device for estimating mental health status in patients with mental illness.

Object: Real-world data from wearable devices has the potential to understand mental health status in everyday life. We aimed to investigate the feasibility of estimating mental health status using a wrist-worn wearable device (Fitbit Sense) that measures movement using a 3D accelerometer and optical pulse photoplethysmography (PPG). Methods: Participants were 110 patients with mental illnesses from different diagnostic groups. The study was undertaken between 1 October 2020 and 31 March 2021. Participants wore a Fitbit Sense on their wrist and also completed the State-Trait Anxiety Inventory (STAI), Positive and Negative Affect Schedule (PANAS), and EuroQol 5 dimensions 5-level (EQ-5D-5L) during the study period. To determine heart rate (HR) variability (HRV), we calculated the sdnn (standard deviation of the normal-to-normal interval), coefficient of variation of R-R intervals, and mean HR separately for each sleep stage and the daytime. The association between mental health status and HR and HRV was analyzed. Results: The following significant correlations were found in the wake after sleep onset stage within 3 days of mental health status assessment: sdnn, HR and STAI scores, HR and PANAS scores, HR and EQ-5D-5L scores. The association between mental health status and HR and HRV was stronger the closer the temporal distance between mental health status assessment and HR measurement. Conclusion: A wrist-worn wearable device that measures PPG signals was feasible for use with patients with mental illness. Resting state HR and HRV could be used as an objective assessment of mental health status within a few days of measurement.

Development and acceptability testing of a decision aid for considering whether to reduce antipsychotics in individuals with stable schizophrenia.

AIM: Continued antipsychotic treatment is the key to preventing relapse. Maintenance antipsychotic monotherapy and optimal dose use are recommended for individuals with stable schizophrenia because of their undesirable effects. Decision aids (DAs) are clinical conversation tools that facilitate shared decision-making (SDM) between patients and health-care providers. This study aimed to describe the development process and results of acceptability testing of a DA for individuals with stable schizophrenia, considering (i) whether to continue high-dose antipsychotics or reduce to the standard dose and (ii) whether to continue two antipsychotics or shift to monotherapy. METHODS: A DA was developed according to the guidelines for the appropriate use of psychotropic medications and International Patient Decision Aid Standards (IPDAS). First, a DA prototype was developed based on a previous systematic review and meta-analysis conducted for identifying the effects of continuing or reducing antipsychotic treatment. Second, mixed-method survey was performed among individuals with schizophrenia and health-care providers to modify and finalize the DA. RESULTS: The DA consisted of an explanation of schizophrenia, options to continue high-dose antipsychotics or reduce to the standard dose, options to continue two antipsychotics or shift to monotherapy, pros and cons of each option, and a value-clarification worksheet for each option. The patients (n = 20) reported acceptable language use (75%), adequate information (75%), and well-balanced presentation (79%). Health-care providers (n = 20) also provided favorable overall feedback. The final DA covered six IPDAS qualifying criteria. CONCLUSION: A DA was successfully developed for schizophrenia, considering whether to reduce antipsychotics, which can be used in the SDM process.

The Relationship between Insomnia and Lifestyle-Related Diseases among Japanese Male Truck Drivers.

Previously, insomnia and adverse lifestyle were prevalent among truck drivers, but the association between the two remains unknown in this particular occupational cohort. This study aimed to examine the relationship between insomnia and lifestyle-related diseases among truck drivers. We investigated 875 male truck drivers of the Japan Truck Association, Akita branch, as of July 2020. The definition of insomnia was based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Data from a self-administered questionnaire were merged with health records and health insurance claims data of 2020. In total, 40.1% had either one of the lifestyle-related diseases including hypertension (29.7%), diabetes mellitus (11.7%), and dyslipidemia (24.8%), whereas according to ICSD-3, 13.2% had insomnia. Multivariate logistic regression models demonstrated that individuals with insomnia had approximately 2-fold increased risk of having at least one lifestyle-related disease (p < 0.001), hypertension (p = 0.0027), diabetes mellitus (p = 0.0654) and dyslipidemia (p < 0.001). Occupational characteristics including daily driving hours, driving distance, and travel days were not associated with any lifestyle-related diseases except for an association between short-haul and at least one disease. In conclusion, insomnia is significantly associated with increased risks of lifestyle-related diseases among male truck drivers in Japan.

Exploratory Validation of Sleep-Tracking Devices in Patients with Psychiatric Disorders.

Purpose: Sleep-tracking devices have performed well in recent studies that evaluated their use in healthy adults by comparing them with the gold standard sleep assessment technique, polysomnography (PSG). These devices have not been validated for use in patients with psychiatric disorders. Therefore, we tested the performance of three sleep-tracking devices against PSG in patients with psychiatric disorders. Patients and methods: In total, 52 patients (32 women; 48.1 ± 17.2 years, mean ± SD; 18 patients diagnosed with schizophrenia, 19 with depressive disorder, 3 with bipolar disorder, and 12 with sleep disorder cases) were tested in a sleep laboratory with PSG, along with portable electroencephalography (EEG) device (Sleepgraph), actigraphy (MTN-220/221) and consumer sleep-tracking device (Fitbit Sense). Results: Epoch-by-epoch sensitivity (for sleep) and specificity (for wake), respectively, were as follows: Sleepgraph (0.95, 0.76), Fitbit Sense (0.95, 0.45) and MTN-220/221 (0.93, 0.40). Portable EEG (Sleepgraph) had the best sleep stage-tracking performance. Sleep-wake summary metrics demonstrated lower performance on poor sleep (ice, shorter total sleep time, lower sleep efficiency, longer sleep latency, longer wake after sleep onset). Conclusion: Devices demonstrated similar sleep-wake detecting performance as compared with previous studies that evaluated sleep in healthy adults. Consumer sleep device may exhibit poor sleep stage-tracking performance in patients with psychiatric disorders due to factors that affect the sleep determination algorithm, such as changes in autonomic nervous system activity. However, Sleepgraph, a portable EEG device, demonstrated higher performance in mental disorders than the Fitbit Sense and actigraphy.

Treatment strategy for insomnia disorder: Japanese expert consensus.

Purpose: There is a lack of evidence regarding answers for clinical questions about treating insomnia disorder. This study aimed to answer the following clinical questions: (1) how to use each hypnotic and non-pharmacological treatment differently depending on clinical situations and (2) how to reduce or stop benzodiazepine hypnotics using alternative pharmacological and non-pharmacological treatments. Methods: Experts were asked to evaluate treatment choices based on 10 clinical questions about insomnia disorder using a nine-point Likert scale (1 = "disagree" to 9 = "agree"). The responses of 196 experts were collected, and the answers were categorized into first-, second-, and third-line recommendations. Results: The primary pharmacological treatment, lemborexant (7.3 ± 2.0), was categorized as a first-line recommendation for sleep initiation insomnia, and lemborexant (7.3 ± 1.8) and suvorexant (6.8 ± 1.8) were categorized as the first-line recommendations for sleep maintenance insomnia. Regarding non-pharmacological treatments for primary treatment, sleep hygiene education was categorized as the first-line recommendation for both sleep initiation (8.4 ± 1.1) and maintenance insomnia (8.1 ± 1.5), while multicomponent cognitive behavioral therapy for insomnia was categorized as the second-line treatment for both sleep initiation (5.6 ± 2.3) and maintenance insomnia (5.7 ± 2.4). When reducing or discontinuing benzodiazepine hypnotics by switching to other medications, lemborexant (7.5 ± 1.8) and suvorexant (6.9 ± 1.9) were categorized as first-line recommendations. Conclusion: Expert consensus indicates that orexin receptor antagonists and sleep hygiene education are recommended as first-line treatments in most clinical situations to treat insomnia disorder.

Development and acceptability of a decision aid for anxiety disorder considering discontinuation of benzodiazepine anxiolytic.

Aim: We aimed to develop a decision aid (DA) for individuals with anxiety disorders who consider tapering benzodiazepine (BZD) anxiolytics, and if tapering, tapering BZD anxiolytics with or without cognitive behavioral therapy (CBT) for anxiety. We also assessed its acceptability among stakeholders. Methods: First, we conducted a literature review regarding anxiety disorders to determine treatment options. We cited the results of the systematic review and meta-analysis, which we conducted previously, to describe the related outcomes of two options: tapering BZD anxiolytics with CBT and tapering BZD anxiolytics without CBT. Second, we developed a DA prototype in accordance with the International Patient Decision Aid Standards. We carried out a mixed methods survey to assess the acceptability among stakeholders including those with anxiety disorders and healthcare providers. Results: Our DA provided information such as explanation of anxiety disorders, options of tapering or not tapering BZD anxiolytics (if tapering, the options of tapering BZD anxiolytics with or without CBT) for anxiety disorder, benefits and risks of each option, and a worksheet for value clarification. For patients (n = 21), the DA appeared to be acceptable language (86%), adequate information (81%), and well-balanced presentation (86%). The developed DA was also acceptable for healthcare providers (n = 10). Conclusion: We successfully created a DA for individuals with anxiety disorders who consider tapering BZD anxiolytics, which was acceptable for both patients and healthcare providers. Our DA was designed to assist patients and healthcare providers to involve decision-making about whether to taper BZD anxiolytics or not.

A Comparison between Perceptions of Psychiatric Outpatients and Psychiatrists Regarding Benzodiazepine Use and Decision Making for Its Discontinuation: A Cross-Sectional Survey in Japan.

BACKGROUND: Although long-term use of benzodiazepines and z-drugs (BZDs) is not recommended, little is known about the stakeholders' perceptions. This study aimed to assess and compare the perceptions of BZD use and decision making regarding its discontinuation between psychiatric outpatients and psychiatrists. METHODS: A cross-sectional survey was conducted. RESULTS: Of 104 outpatients, 92% were taking hypnotics and 96% were taking anxiolytics for ≥a year, while 49% were willing to taper hypnotic/anxiolytics within a year of starting. Most psychiatrists felt that "patient and psychiatrist make the decision together on an equal basis" compared to patients (p < 0.001), while more patients felt that "the decision is (was) made considering the psychiatrists' opinion" compared to psychiatrists (p < 0.001). Of 543 psychiatrists, 79% reported "patients were not willing to discontinue hypnotic/anxiolytic" whereas a certain number of patients conveyed "psychiatrists did not explain in enough detail about hypnotic/anxiolytic discontinuation such as procedure (18.3%), timing (19.2%), and appropriate condition (14.4%)". CONCLUSION: The results suggest that the majority of psychiatric outpatients were taking hypnotic/anxiolytics for a long time against their will. There might be a difference in perceptions toward hypnotic/anxiolytic use and decision making for its discontinuation between psychiatric outpatients and psychiatrists. Further research is necessary to fill this gap.

Physicians' attitudes toward hypnotics for insomnia: A questionnaire-based study.

Introduction: Benzodiazepines and non-benzodiazepines are still widely prescribed despite safety concerns and the introduction of novel hypnotics (orexin receptor antagonists [ORA] and melatonin receptor agonists [MRA]), which may be influenced by physicians' attitudes toward hypnotics. Methods: A questionnaire survey was administered to 962 physicians between October 2021 and February 2022, investigating frequently prescribed hypnotics and the reasons for their selection. Results: ORA were the most frequently prescribed at 84.3%, followed by non-benzodiazepines (75.4%), MRA (57.1%), and benzodiazepines (54.3%). Compared to non-frequent prescribers of hypnotics, a logistic regression analysis showed that frequent ORA prescribers were more concerned with efficacy (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.01-2.54, p = 0.044) and safety (OR: 4.52, 95% CI: 2.99-6.84, p < 0.001), frequent MRA prescribers were more concerned with safety (OR: 2.48, 95% CI: 1.77-3.46, p < 0.001), frequent non-benzodiazepine prescribers were more concerned with efficacy (OR: 4.19, 95% CI: 2.91-6.04, p < 0.001), and frequent benzodiazepine prescribers were more concerned with efficacy (OR: 4.19, 95% CI: 2.91-6.04, p < 0.001) but less concerned with safety (OR: 0.25, 95% CI: 0.16-0.39, p < 0.001). Discussion: This study suggested that physicians believed ORA to be an effective and safe hypnotic and were compelled to prescribe benzodiazepine and non-benzodiazepine frequently, choosing efficacy over safety.

Management of unspecified anxiety disorder: Expert consensus.

AIMS: Treatment guidelines with respect to unspecified anxiety disorder have not been published. The aim of this study was to develop a consensus among field experts on the management of unspecified anxiety disorder. METHODS: Experts were asked to evaluate treatment choices based on eight clinical questions concerning unspecified anxiety disorder using a nine-point Likert scale (1 = "disagree" to 9 = "agree"). According to the responses from 119 experts, the choices were categorized into first-, second-, and third-line recommendations. RESULTS: Benzodiazepine anxiolytic use was not categorized as a first-line recommendation for the primary treatment of unspecified anxiety disorder, whereas multiple nonpharmacological treatment strategies, including coping strategies (7.9 ± 1.4), psychoeducation for anxiety (7.9 ± 1.4), lifestyle changes (7.8 ± 1.5), and relaxation techniques (7.4 ± 1.8), were categorized as first-line recommendations. Various treatment strategies were categorized as first-line recommendations when a benzodiazepine anxiolytic drug did not improve anxiety symptoms, that is, differential diagnosis (8.2 ± 1.4), psychoeducation for anxiety (8.0 ± 1.5), coping strategies (7.8 ± 1.5), lifestyle changes (7.8 ± 1.5), relaxation techniques (7.2 ± 1.9), and switching to selective serotonin reuptake inhibitors (SSRIs) (7.0 ± 1.8). These strategies were also highly endorsed when tapering the dosage of or discontinuing benzodiazepine anxiolytic drugs. There was no first-line recommendation regarding excusable reasons for continuing benzodiazepine anxiolytics. CONCLUSIONS: The field experts recommend that benzodiazepine anxiolytics should not be used as a first-line option for patients with unspecified anxiety disorder. Instead, several nonpharmacological interventions and switching to SSRIs were endorsed for the primary treatment of unspecified anxiety disorder and as alternatives to benzodiazepine anxiolytics.

Effects of Japanese policies and novel hypnotics on long-term prescriptions of hypnotics.

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.

Clinical practice for unspecified anxiety disorder in primary care.

Aim: Clinicians face difficulties in making treatment decisions for unspecified anxiety disorder due to the absence of any treatment guidelines. The objective of this study was to investigate how familiar and how often primary care physicians use pharmacological and nonpharmacological approaches to manage the disorder. Methods: A survey was conducted among 117 primary care physicians in Japan who were asked to assess the familiarity of using each treatment option for unspecified anxiety disorder on a binary response scale (0 = "unfamiliar," 1 = "familiar") and the frequency on a nine-point Likert scale (1 = "never used," 9 = "frequently used"). Results: While several benzodiazepine anxiolytics were familiar to primary care physicians, the frequencies of prescribing them, including alprazolam (4.6 ± 2.6), ethyl loflazepate (3.6 ± 2.4), and clotiazepam (3.5 ± 2.3), were low. In contrast, certain nonpharmacological options, including lifestyle changes (5.4 ± 2.3), coping strategies (5.1 ± 2.7), and psychoeducation for anxiety (5.1 ± 2.7), were more commonly utilized, but to a modest extent. When a benzodiazepine anxiolytic drug failed to be effective, primary care physicians selected the following management strategies to a relatively high degree: differential diagnosis (6.4 ± 2.4), referral to a specialist hospital (5.9 ± 2.5), lifestyle changes (5.2 ± 2.5), and switching to selective serotonin reuptake inhibitor (5.1 ± 2.4). Conclusion: Primary care physicians exercise caution when prescribing benzodiazepine anxiolytics for unspecified anxiety disorder. Nonpharmacological interventions and switching to SSRI are modestly employed as primary treatment options and alternatives to benzodiazepine anxiolytics. To ensure the safe and effective treatment of unspecified anxiety disorder in primary care, more information should be provided from field experts.

Attitudes and Difficulties Associated with Benzodiazepine Discontinuation.

Long-term use of benzodiazepine receptor agonists (BZDs) may depend on clinicians' BZD discontinuation strategies. We aimed to explore differences in strategies and difficulties with BZD discontinuation between psychiatrists and non-psychiatrists and to identify factors related to difficulties with BZD discontinuation. Japanese physicians affiliated with the Japan Primary Care Association, All Japan Hospital Association, and Japanese Association of Neuro-Psychiatric Clinics were surveyed on the following items: age group, specialty (psychiatric or otherwise), preferred time to start BZD reduction after improvement in symptoms, methods used to discontinue, difficulties regarding BZD discontinuation, and reasons for the difficulties. We obtained 962 responses from physicians (390 from non-psychiatrists and 572 from psychiatrists), of which 94.0% reported difficulty discontinuing BZDs. Non-psychiatrists had more difficulty with BZD discontinuation strategies, while psychiatrists had more difficulty with symptom recurrence/relapse and withdrawal symptoms. Psychiatrists used more candidate strategies in BZD reduction than non-psychiatrists but initiated BZD discontinuation after symptom improvement. Logistic regression analysis showed that psychosocial therapy was associated with less difficulty in BZD discontinuation (odds ratio, 0.438; 95% confidence interval, 0.204-0.942; p = 0.035). Educating physicians about psychosocial therapy may alleviate physicians' difficulty in discontinuing BZDs and reduce long-term BZD prescriptions.

Preterm toddlers have low nighttime sleep quality and high daytime activity.

A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers' waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development.