Masakazu Hatano

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.

A variety of medications contribute to the risk of postoperative delirium (POD) in older adults. This multicenter retrospective study aimed to investigate the relationship between the number of delirium-associated medication types and the incidence of POD. Patients aged greater than or equal to 70 years who underwent surgery under general anesthesia were included. Odds ratios (ORs) and 95% confidence intervals were estimated via multivariate logistic regression analysis, using patients not receiving delirium-associated medications as the reference group. Delirium-associated medications were selected from seven medication classes: benzodiazepines, non-benzodiazepines, opioids, antiparkinsonian agents, glucocorticoids, H1-antihistamines, and H2-antihistamines. A total of 4562 patients were included in the analysis. The overall incidence of POD was 7.7% (352/4562) and increased progressively with the number of delirium-associated medication types, from 6.0% among patients receiving none to 31.0% among those receiving four or more types. After adjusting for other delirium-related factors, the ORs of POD were significantly higher in patients receiving delirium-associated medications than in those receiving none and increased with the number of medication types. Sensitivity analyses confirmed the robustness of these findings. Our findings suggest that a higher number of delirium-associated medications is associated with an increased risk of POD in older adults, warranting preoperative medication review.

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.