Kenji Sakuma

AIM: This network meta-analysis of randomized controlled trials (RCTs) aimed to investigate which hypnotics are associated with the most favorable sleep architecture and respiratory outcomes in adults with obstructive sleep apnea. METHODS: Primary outcomes included total sleep time (TST) and apnea-hypopnea index (AHI) during TST. Other outcomes were rapid eye movement (REM) sleep time, latency to persistent sleep (LPS), wake after sleep onset (WASO), sleep efficiency (SE), AHI during non-REM or REM sleep, mean peripheral oxygen saturation (SpO2) during TST, mean SpO2 nadir during TST, arousal index (AI), all-cause discontinuation, adverse event-related discontinuation, and incidence of individual adverse events. Effect sizes with 95% confidence intervals were calculated. RESULTS: This systematic review included 32 RCTs (n = 1871, average age = 51.60 years, 62.52% male, mean AHI = 23.60). Our network meta-analysis evaluated brotizolam, daridorexant, eszopiclone, flurazepam, lemborexant, nitrazepam, ramelteon, temazepam, triazolam, zaleplon, zolpidem, zopiclone, and placebo. Compared with placebo, lemborexant increased TST, REM sleep time, and SE and decreased LPS and WASO, whereas both daridorexant and zolpidem increased TST and SE and decreased WASO. These three medications demonstrated respiratory safety and discontinuation profiles similar to those of placebo. Eszopiclone increased TST and SE and decreased LPS, WASO, AHI during TST, and AI, but its effects on LPS, WASO, AHI during TST, and AI disappeared in the sensitivity analysis, excluding continuous positive airway pressure titration studies. CONCLUSION: Our network meta-analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice.

ABSTRACT Objective To examine the characteristics associated with happiness in Japanese individuals with schizophrenia. Methods A self‐reported online survey was conducted in 2022 among individuals aged 20–75 years, including 223 and 1776 individuals with and without schizophrenia, respectively. We used a modified Poisson regression to assess the factors associated with happiness by calculating the age‐ and sex‐adjusted prevalence ratios (PRs). We examined within‐schizophrenia group differences by age and sex strata, and compared these stratified PRs between groups with and without schizophrenia. Results Among participants with schizophrenia, happiness was significantly associated with self‐rated health status (PR = 1.75), Ikigai (PR = 5.02), depressive symptoms (PR = 0.43), perceived stress (PR = 0.52), cognitive social capital (PR = 2.07), structural social capital (PR = 1.70), social support (PR = 2.40), close friends (PR = 1.88), close relatives (PR = 2.34), and a cohabiting partner (PR = 1.57). Within the schizophrenia group, sex differences were significant for cognitive social capital (men: PR = 3.45; women: PR = 1.43) and cohabiting partners (men: PR = 2.26; women: PR = 1.25), whereas no significant age differences were found. Factors demonstrating a stronger association in participants with schizophrenia than in those without schizophrenia included: Ikigai (with, PR = 5.02; without, PR = 2.91), cognitive social capital (with, PR = 2.07; without, PR = 1.49), and structural social capital (with, PR = 1.70; without, PR = 1.24). Conclusion Happiness in individuals with schizophrenia is associated with physical, mental, and social factors, with social factors exhibiting sex‐related differences.

BACKGROUND: The optimal duration for maintaining antidepressant treatment in individuals with obsessive-compulsive disorder (OCD) who achieve symptom stabilization remains unclear. METHODS: This systematic review and pairwise meta-analysis of double-blind randomized placebo-controlled trials (DBRPCTs) compared antidepressant maintenance and antidepressant discontinuation groups in terms of relapse rate at each DBRPCT study endpoint (primary outcome), OCD symptom improvement, all-cause discontinuation, and adverse event-related discontinuation. Furthermore, relapse rates at 4, 8, 12, 16, 20, and 24 weeks were compared between the groups. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. The absolute risk reduction (ARR) and number needed to treat to benefit (NNTB) for relapse rates were also estimated. RESULTS: Nine trials (n = 1084; mean age: 32.8 years; proportion of males: 53.3%) were included. The antidepressant maintenance group had lower relapse rates at each DBRPCT study endpoint (RR [95% CI] = 0.53 [0.42-0.68]; ARR = 21.0%; NNTB = 5) and lower all-cause and adverse event-related discontinuation rates than the antidepressant discontinuation group. The maintenance group also exhibited lower relapse rates at 4 weeks (RR [95% CI] = 0.47 [0.31-0.70]; ARR: not significant; NNTB: not significant), 8 weeks (0.42 [0.31-0.57]; 12.0%; 8), 12 weeks (0.43 [0.32-0.56]; 18.0%; 6), 16 weeks (0.41 [0.32-0.52]; 25.0%; 4), 20 weeks (0.43 [0.34-0.53]; 26.0%; 4), and 24 weeks (0.42 [0.33-0.52]; 27.0%; 4) than the discontinuation group. Moreover, the maintenance group outperformed the discontinuation group regarding OCD symptom improvement. CONCLUSIONS: Individuals with OCD may benefit from continued antidepressant treatment, provided that it is well tolerated.

BACKGROUND: In order to appraise the risk-benefit balance of the three available dual orexin receptor antagonists (DORAs; daridorexant, lemborexant, and suvorexant) for the management of adults with insomnia, we conducted a systematic review and random-effects model network meta-analysis. METHODS: Included were all published double-blind, randomized, placebo-controlled trials of these agents. Outcomes included subjective time to sleep onset at month 1 (sTSO, primary), subjective total sleep time at month 1 (sTST, co-primary), subjective wake after sleep onset at month 1, Insomnia Severity Index scores at month 1, all-cause discontinuation, discontinuation due to adverse events, and the incidence of individual adverse events such as somnolence, dizziness, falls, headache, nasopharyngitis, and upper respiratory tract infection. RESULTS: This meta-analysis included eight trials (5198 adults, average age = 56.33 years, 67.84% female). The treatment arms included daridorexant 25 mg/day (DAR25), daridorexant 50 mg/day (DAR50), lemborexant 5 mg/day (LEM5), lemborexant 10 mg/day (LEM10), suvorexant 20 mg/day (15 mg/day for people ≥65years, SUV20/15), and placebo. All active-treatments outperformed placebo in terms of all efficacy outcomes. The standardized mean difference (95% CI) in primary outcomes ranged from; sTSO: -0.430 (-0.568, -0.292) for LEM10 to -0.164 (-0.296, -0.031) for SUV20/15 and sTST: -0.475 (-0.593, -0.357) for DRA50 to -0.206 ( -0.330, -0.082) for LEM5. An additional sensitivity analysis suggested that DRA25, LEM10, and SUV20/15 were associated with a higher incidence of somnolence compared to a placebo. CONCLUSIONS: Considering that there is no evidence that DORAs are associated with physiological tolerance, withdrawal symptoms, or rebound insomnia when abruptly discontinued, and that sleep architecture is not adversely affected, the DORAs appear to be a favorable choice in managing insomnia disorder in adults.

BACKGROUND: With 30%-50% of people with bipolar depression (BDep) not responding to multiple pharmacological treatments, alternative therapies are needed. Accelerated intermittent theta burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (L-DLPFC) has been employed for individuals with pharmacological treatment-resistant major depressive disorder (TR-MDD). Imaging studies have revealed reduced regional activity of the L-DLPFC for both TR-MDD and pharmacological treatment-resistant BDep (TR-BDep), suggesting that aiTBS over the L-DLPFC may be beneficial for people with TR-BDep. METHODS: A 6-week, double-blind, sham-controlled, randomized trial will be conducted to compare the efficacy and safety of aiTBS to the L-DLPFC in people with TR-BDep (jRCTs042240019). Fifty iTBS sessions (1800 pulses/session) will be delivered in 10 daily sessions over 5 consecutive days at 90% resting motor threshold. This aiTBS protocol is termed as Fujita Neuromodulation Therapy for Bipolar Depression (FNT-BD). Twenty-two participants (both sexes, aged 18-64 years) with TR-BDep (DSM-5-TR, Type I) will be recruited. The response rate at any given week of follow-up will be the primary efficacy outcome, defined as a reduction of ≥50% in the Montgomery Åsberg Depression Rating Scale (MADRS) score. Other outcomes will include MADRS score changes, remission rate (10 ≥ MADRS score), Clinical Global Impression-Improvement score, Clinical Global Impression-Severity score, discontinuation rate, and incidence of individual adverse events. RESULTS: We anticipate that individuals who receive the aiTBS treatment show significant improvement in depressing symptoms compared to those receiving sham treatment. CONCLUSIONS: This study will provide valuable evidence for both patients with TR-BDep and clinicians.