Mood Stabilizers and Antipsychotics for Acute Mania: Systematic Review and Meta-Analysis of Augmentation Therapy vs Monotherapy From the Perspective of Time to the Onset of Treatment Effects

Background: Existing meta-analytic evidence on bipolar mania treatment has revealed that augmentation therapy (AUG) with antipsychotics and mood stabilizers is more effective than monotherapy. However, the speed of the onset of treatment effects and subsequent changes in risk/benefit are unclear. Methods: We searched the Cochrane CENTRAL, MEDLINE, and EMBASE databases until January 2021. Our primary outcomes were response and tolerability. We set 3 time points: 1, 3, and 6 weeks after randomization. Results: Seventeen studies compared AUG therapy and MS monotherapy (comparison 1), and 8 studies compared AUG therapy and antipsychotics monotherapy (comparison 2). In comparison 1, AUG therapy resulted in significantly more responses than monotherapy, with an odds ratio of 1.45 (95% confidence interval [CI]: 1.17 to 1.80) at 3 weeks and 1.59 (95% CI: 1.28 to 1.99) at 6 weeks. Significant improvement was observed in the first week with a standardized mean difference of −0.25 (95% CI: −0.38 to −0.12). In comparison 2, AUG therapy was significantly more effective than monotherapy, with an odds ratio of 1.73 (95% CI: 1.25 to 2.40) at 3 weeks and 1.74 (95% CI: 1.11 to 2.73) at 6 weeks. Significant improvement was observed in the first week with an standardized mean difference of −0.23 (95% CI: −0.39 to −0.07). Regarding tolerability, there was no significant difference between AUG therapy and monotherapy at 3 and 6 weeks in both comparisons. Conclusions: Early AUG therapy should be considered, as it has shown efficacy from weeks 1 to 6, although attention to side effects is necessary for acute mania treatment

Genetic Elucidation for Response of Flowering Time to Ambient Temperatures in Asian Rice Cultivars

Climate resilience of crops is critical for global food security. Understanding the genetic basis of plant responses to ambient environmental changes is key to developing resilient crops. To detect genetic factors that set flowering time according to seasonal temperature conditions, we evaluated differences of flowering time over years by using chromosome segment substitution lines (CSSLs) derived from japonica rice cultivars "Koshihikari" x "Khao Nam Jen", each with different robustness of flowering time to environmental fluctuations. The difference of flowering times in 9 years' field tests was large in "Khao Nam Jen" (36.7 days) but small in "Koshihikari" (9.9 days). Part of this difference was explained by two QTLs. A CSSL with a "Khao Nam Jen" segment on chromosome 11 showed 28.0 days' difference; this QTL would encode a novel flowering-time gene. Another CSSL with a segment from "Khao Nam Jen" in the region around Hd16 on chromosome 3 showed 23.4 days" difference. A near-isogenic line (NIL) for Hd16 showed 21.6 days' difference, suggesting Hd16 as a candidate for this QTL. RNA-seq analysis showed differential expression of several flowering-time genes between early and late flowering seasons. Low-temperature treatment at panicle initiation stage significantly delayed flowering in the CSSL and NIL compared with "Koshihikari". Our results unravel the molecular control of flowering time under ambient temperature fluctuations

Neutron capture cross section measurements of 120

Preliminary neutron capture cross section of 120Sn, 122Sn and 124Sn were obtained in the energy range from 20 meV to 4 keV with the array of germanium detectors in ANNRI at MLF,J-PARC. The results of 120Sn, 122Sn and 124Sn were obtained by normalizing the relative cross sections to the data in JENDL-4.0 at the largest 426.7-, 107.0- and 62.05-eV resonances, respectively. The 67.32- and 150-eV resonances for 120Sn and the 579- and 950-eV resonances for 124Sn which are listed in JENDL-4.0 and/or ENDF/B VII.1 were not observed

Clozapine and Antipsychotic Monotherapy

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

Background: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine. Methods: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study. Results: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (r s = 0.531, P = 1.032 × 10−4). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS. Conclusion: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families