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.

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.

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.

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.

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.

Severity of Depressive Symptoms is Associated with Venous Thromboembolism in Hospitalized Patients with a Major Depressive Episode.

PURPOSE: A major depressive episode is a risk factor for venous thromboembolism (VTE) in psychiatric inpatients. However, it is unclear whether the severity of depressive symptoms or duration of the current depressive episode is associated with VTE. Further, the VTE prevalence among hospitalized patients with a major depressive episode receiving electroconvulsive therapy is unknown. This retrospective study examined factors associated with VTE among hospitalized patients with a major depressive episode and estimated the prevalence of VTE in such patients who underwent electroconvulsive therapy. PATIENTS AND METHODS: Patients with a major depressive episode hospitalized in the Department of Neuropsychiatry at Akita University Hospital between January 2018 and December 2020 were included. Data from the first week of hospitalization were extracted from medical records. VTE was diagnosed based on the findings of computed tomography. To evaluate whether the severity of depressive symptoms or duration of the current depressive episode was associated with VTE, logistic regression analysis was conducted after adjusting for covariates with known VTE risk factors (antidepressants, antipsychotics, and physical comorbidities). RESULTS: We analyzed 133 patients; of these, 14 were diagnosed with asymptomatic VTE. The severity of depressive symptoms (odds ratio: 1.220, 95% confidence interval: 1.081-1.377, p = 0.001) was significantly associated with VTE. The prevalence of VTE among those receiving electroconvulsive therapy was 35% (7/20). CONCLUSION: The prevalence of VTE was 35% among patients receiving in-hospital electroconvulsive therapy for a major depressive episode. VTE should be considered for hospitalized patients with severe depressive symptoms and patients receiving in-hospital electroconvulsive therapy for a major depressive episode.

Prevalence of Asymptomatic Venous Thromboembolism in Depressive Inpatients.

PURPOSE: While depression has been recognized as a risk factor for venous thromboembolism (VTE), the prevalence of VTE in depressed inpatients has never been investigated. The aim of this study was thus to examine VTE prevalence and factors associated with VTE in depressed inpatients. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study of consecutive depressed inpatients (n = 94) from January 1, 2018, to June 30, 2019, at the psychiatry department of Akita University Hospital. As part of our clinical routine, depressed inpatients were screened for VTE using D-dimer, and patients who screened positive underwent enhanced CT to examine VTE. A variety of data was extracted from medical records, including, amongst others, age, sex, body mass index, diagnoses of psychiatric disorders, total scores on the 17-item Hamilton Depression Rating Scale, duration of current depressive episode, daily dosages of antidepressants and antipsychotics, catatonia, and physical restraint. RESULTS: VTE was detected in 8.5% of depressed inpatients. There were no significant differences between VTE-positive and VTE-negative inpatients regarding any of the considered factors. CONCLUSION: Our analysis shows a VTE prevalence of 8.5% in depressed inpatients, higher than that of 2.3% reported in a previous study in hospitalized patients with psychiatric disorders including depression. This emphasizes the importance of VTE screening for depressive inpatients.

Orexin/hypocretin levels in the cerebrospinal fluid and characteristics of patients with myotonic dystrophy type 1 with excessive daytime sleepiness.

PURPOSE: Myotonic dystrophy type 1 (DM1) is often characterized by excessive daytime sleepiness (EDS) and sleep-onset rapid eye movement periods caused by muscleblind-like protein 2. The EDS tends to persist even after treatment of sleep apnea. We measured the cerebrospinal fluid (CSF) orexin levels in DM1 patients with EDS and compared the clinical characteristics with narcolepsy type 1 and idiopathic hypersomnia (IHS) patients. PATIENTS AND METHODS: We measured the CSF orexin levels in 17 DM1 patients with EDS and evaluated subjective sleepiness using the Epworth Sleepiness Scale (ESS), objective sleepiness using mean sleep latency (MSL), and sleep apnea using apnea-hypopnea index (AHI). We compared the ESS scores and MSL between decreased (≤200 pg/mL) and normal (>200 pg/mL) CSF orexin group in DM1 patients. Furthermore, we compared the CSF orexin levels, ESS scores, MSL, and AHI among patients with DM1, narcolepsy type 1 (n=46), and IHS (n=30). RESULTS: Seven DM1 patients showed decreased CSF orexin levels. There were significant differences in the ESS scores and MSL between decreased and normal CSF orexin groups in DM1 patients. The ESS scores showed no significant difference among patients with DM1, narcolepsy type 1, and IHS. The MSL in DM1 and IHS patients were significantly higher than narcolepsy type 1 patients (p=0.01, p<0.001). The AHI in DM1 patients was significantly higher than narcolepsy type 1 patients (p=0.042) and was insignificantly different from IHS patients. The CSF orexin levels in DM1 patients were significantly lower than IHS patients and higher than narcolepsy type 1 patients (p<0.001, p<0.001). CONCLUSION: The CSF orexin levels of DM1 patients moderately decreased compared to those of IHS patients as the control group. However, the EDS of DM1 patients may not be explained by only orexin deficiency.