Masakazu Hatano

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.

BACKGROUND: Cognitive dysfunction has a significant impact on social functioning, such as employment, in patients with schizophrenia. However, existing cognitive assessments are time-consuming, impose a significant burden on patients, and require specialized training for evaluators, making them impractical for routine clinical use. Therefore, the present study investigated whether a simple and novel assessment tool, called Psychomotor Function Tests (PFT), correlates with existing Neuropsychological Tests (NT) and assessments with the Life Assessment Scale for the Mentally Ill (LASMI), which evaluates social functioning, including employment. METHODS: Cognitive function was examined in 24 patients with schizophrenia using NT (the Japanese Adult Reading Test, Trail Making Test (TMT), and word fluency test) and tablet-based PFT, while social functioning was evaluated using LASMI. Twenty-four healthy controls (HCs) underwent the same cognitive assessments. RESULTS: Psychomotor function, as evaluated by the choice reaction time, compensatory tracking test, and rapid visual information processing, was significantly worse in patients with schizophrenia than in HCs (p < 0.001). Furthermore, the composite score of PFT correlated with the time required for TMT (r = -0.707, -0.637) and LASMI subscales related to work, endurance & stability, self-recognition, required skills, and retention skills (r = -0.640, -0.689, -0.634, -0.420, -0.548). CONCLUSION: PFT correlated with existing NT, which are widely used in cognitive function assessments. Cognitive function examined by PFT was closely associated with social functioning. These results suggest the potential of PFT for evaluating cognitive function in routine clinical settings for patients with schizophrenia.

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/Objectives: The risk of fractures associated with immune checkpoint inhibitors (ICIs) is increasing; however, the relationship between fracture risk and potential factors, such as osteoporosis and hyperthyroidism, remains unclear. Methods: Using VigiBase, the World Health Organization's global pharmacovigilance database, we investigated the signals for osteoporosis, hyperthyroidism, and fractures associated with ICIs (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and tremelimumab) by calculating information components (ICs) and their 95% confidence intervals (CIs). Furthermore, we estimated the association between the occurrence of fractures in patients receiving ICIs and osteoporosis or hyperthyroidism. Results: Signals of hyperthyroidism (IC = 4.66, 95% CI: 4.58–4.73), but not osteoporosis (IC = −1.79, 95% CI: −2.22 to −1.36) or fractures (IC = −0.21, 95% CI: −0.36 to −0.06), were detected in patients using ICIs. Osteoporosis (odds ratio: 118.00, 95% CI: 61.00–230.00) was associated with an increased reporting frequency of fractures related to ICIs, whereas hyperthyroidism (odds ratio: 0.60, 95% CI: 0.19–1.87) was not associated with such an increase. Conclusions: The VigiBase analysis indicates that the use of ICIs does not increase the reporting frequency of osteoporosis or fractures. Additionally, hyperthyroidism did not increase the reporting frequency of fractures associated with ICIs.