Optimal dose for the efficacy of asenapine in patients with schizophrenia: Real-world data.

AIMS: A meta-analysis of short-term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose-response to asenapine in a real-world setting is still unclear. Additionally, the dose-response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real-world setting. METHODS: This study conducted post-marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression-Global Improvement (CGI-I) scale, which has seven categories. RESULTS: A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI-I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. CONCLUSION: These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings.

Divergence of dose-response with asenapine: a cluster analysis of randomized, double-blind, and placebo control study.

BACKGROUND: Differences in psychiatric background and dose-response to asenapine in patients with schizophrenia were examined based on efficacy and safety, using data obtained in a double-blind, placebo-controlled trial. METHODS: Patients with schizophrenia were classified into three clusters by a cluster analysis based on the Positive and Negative Symptom Scale (PANSS) subscores at baseline, using the data from a 6-week, double-blind, placebo-controlled trial. PANSS Marder factor scores were calculated for each cluster. The efficacy of 10 or 20 mg/day of asenapine on PANSS score was used as the primary endpoint, with the incidence of adverse events evaluated as the secondary endpoint. RESULTS: A total of 529 asenapine-treated patients were classified into 3 clusters: Cluster-P with the higher scores in positive symptoms, disorganized thoughts, and hostility/excitement, Cluster-N with higher scores in negative symptoms, and Cluster-L with overall lower scores. In Cluster-N and Cluster-L, both 10 and 20 mg/day groups showed significant improvement in PANSS scores, while only the 20 mg/day group showed a significant difference in Cluster-P. Cluster-N and Cluster-L had differences in the incidence of adverse events, but this was not seen in Cluster-P. CONCLUSIONS: The efficacy and safety of asenapine 10 and 20 mg/day differed between the 3 clusters of patients. This suggests that background information regarding baseline psychiatric symptoms may affect the therapeutic response in patients with schizophrenia.

Sevoflurane in electroconvulsive therapy: A systematic review and meta-analysis of randomised trials.

Sevoflurane is the most commonly used inhaled anaesthetic in electroconvulsive therapy (ECT). The objective of this study was to provide an up-to-date and comprehensive review on how the use of sevoflurane affects seizure adequacy (seizure duration and postictal suppression index [PSI]) and circulatory dynamics in ECT. We performed a meta-analysis of RCTs that investigated seizure adequacy and circulatory dynamics in patients treated with ECT using sevoflurane (sevoflurane group) and intravenous anaesthetics (non-sevoflurane group). A total of 12 RCTs (377 patients and 1339 ECT sessions) were included. Sevoflurane significantly decreased the electroencephalogram (EEG) seizure durations in comparison with intravenous anaesthetics, whereas no significant difference was observed in PSI (EEG: 9 studies, standardized mean difference (SMD) = 0.74, 95% confidence interval (CI) = -1.11 to -0.38, p = 0.0002; PSI: 4 studies, SMD = -0.06, CI -0.13 to 0.25, p = 0.59). The use of sevoflurane in ECT significantly increased heart rate (HR) compared with intravenous anaesthetics (9 studies, SMD = 0.31, CI 012-0.51, p = 0.004). In the pre-planned subgroup analysis, sevoflurane significantly reduced seizure duration compared with other types of anaesthetics, including propofol, barbiturates and ketamine. Furthermore, it was found that the risk of adverse events in ECT with sevoflurane were not significantly different from intravenous anaesthetics (6 studies, risk ratio = 1.33, CI 0.95-1.86, p = 0.09), with agitaion being the most common adverse effects. The results of our study suggest that using sevoflurane for ECT significantly reduces seizure duration, increases maximum HR and brings about no difference in the adverse event risk compared with those using intravenous anaesthetics for ECT. Therefore, there may not be compelling evidence favouring sevoflurane use for ECT, except in cases where intravenous access is difficult.