Kenji Sakuma

The long-term relapse risk after antipsychotic discontinuation, relative to maintenance therapy, remains unclear in adults with first-episode non-affective psychosis (FENAP) stabilized on antipsychotics. This pairwise meta-analysis employing a random-effects model included randomized controlled trials (RCTs) that compared antipsychotic discontinuation with maintenance treatment in adults with stabilized FENAP. Relapse rates were compared at matched time points (1, 2, 3, 6, 9, 12 [primary outcome], 15, 18, 21, and 24 months) between the discontinuation and maintenance groups to more accurately investigate the temporal relapse trend. Risk ratios (RRs) and absolute risk reductions (ARRs) with 95% confidence intervals (CIs) were calculated. This review identified 12 RCTs that included 1133 adults (60.1% male; mean age: 27.3 years). No statistically significant difference in relapse rates was observed between the maintenance and discontinuation groups at 1 month. However, most participants in the discontinuation group were still receiving antipsychotics at 1 month due to gradual tapering. Significant differences were observed at all subsequent time points. At 12 months, the RR of relapse in the maintenance group versus the discontinuation group was 0.45 (95% CI: 0.35-0.57; p < 0.001; I²=11.1%). Relapse rates at 12 months were 21.0% and 53.3% in the maintenance and discontinuation groups, respectively. From 2 to 24 months, RRs remained stable (0.45-0.54). The ARR was 6.0% at 2 months, gradually increasing to 20.0% by 6 months and 32.0% by 12 months, and remaining stable through 24 months. In conclusion, continuing antipsychotic treatment in clinically stable FENAP significantly reduces the risk of relapse for up to 24 months.

OBJECTIVE: This systematic review and meta-analysis of six randomized controlled trials aimed to investigate the temporal changes in the efficacy and safety of psilocybin treatment for major depressive disorder (MDD). METHODS: Separate meta-analyses were conducted for standard-dose psilocybin (25 mg/session, or 20-30 mg/70 kg/session) and low-dose psilocybin (10 mg/session or 15.05 mg/70 kg/session) subgroups. Control conditions included placebo, waiting-list control, niacin, or psilocybin 1 mg. RESULTS: Standard-dose psilocybin was superior to control in reducing depressive symptoms (standardized mean difference [SMD]: -1.05; 95% confidence intervals [CIs]: -1.60 to -0.50, p = 0.0002, I2 = 75%, K = 4). Sensitivity analysis excluding studies with waiting-list controls supported the superiority of standard-dose psilocybin compared with control without considerable heterogeneity (SMD: -0.70; 95% CI: -1.03 to -0.36, p < 0.0001, I2 = 43%, K = 2). This sensitivity analysis included two double-blind trials that incorporated manualized psilocybin-assisted psychotherapy. Compared with controls, standard-dose psilocybin was associated with higher response (risk ratio [RR]: 2.34; 95% CI: 1.52-3.60, p = 0.0001, I2 = 0%) and remission rates at 2-3 weeks post-treatment (RR: 3.38; 95% CI: 1.88-6.08, p < 0.0001, I2 = 0%), with response rate at 6-12 weeks post-treatment (RR: 2.61; 95% CI: 1.45-4.71, p = 0.001, I2 = 0%). Moreover, standard-dose psilocybin was related to lower all-cause discontinuation compared with control (RR: 0.39; 95% CI: 0.18-0.87, p = 0.02, I2 = 0%). Standard-dose psilocybin was associated with a higher incidence of headache (RR: 2.06; 95% CI: 1.11-3.81, p = 0.02, I2 = 57%) and nausea within 1-9 days post-treatment (RR: 10.20; 95% CI: 3.80-27.39, p < 0.0001, I2 = 0%) compared with the control; however, these symptoms resolved after this period. Low-dose psilocybin demonstrated no superior efficacy compared with the control group. CONCLUSIONS: This meta-analysis indicates that standard-dose psilocybin may represent a promising therapeutic option for MDD treatment. Nonetheless, future research should address the considerable methodological heterogeneity across current trials.

We conducted a retrospective study using medical records from Fujita Health University Hospital to evaluate the treatment discontinuation rates of suvorexant and lemborexant in patients with insomnia and to clarify differences in treatment acceptability. This study included patients newly prescribed suvorexant or lemborexant in the Department of Psychiatry between July 2020 and December 2022. The primary endpoint of the study was the discontinuation rate of suvorexant and lemborexant at 4 weeks. Discontinuation due to adverse events and lack of efficacy were assessed as secondary outcomes. The medical records of 1404 patients who were initiated on a dual orexin receptor antagonist during the study period were reviewed, and 1091 patients were included in the final analysis (suvorexant, 323; lemborexant, 768). We estimated the average treatment effect using the inverse probability of treatment weighting based on the propensity score. Discontinuation rates due to all-cause or adverse events did not differ significantly between the two drugs. However, the discontinuation rate due to lack of efficacy was significantly lower for lemborexant (4.9%; 38/768) compared to suvorexant (7.1%; 23/323), with an odds ratio of 0.63 (95% confidence interval, 0.48-0.83). This exploratory finding suggests a potential difference in treatment acceptability associated with efficacy between suvorexant and lemborexant in routine clinical practice, warranting further investigation.

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.