Low-Intensity Pulsed Ultrasound Maintains Bone Mass After Withdrawal of Human Parathyroid Hormone in Ovariectomized Mice.

The intermittent injection of teriparatide, a recombinant fragment of human parathyroid hormone (PTH 1-34), activates anabolic activity on bone turnover. However, the PTH administration period is limited to 2 years. Thus, sequential therapy after discontinuation of PTH is required. Low-intensity pulsed ultrasound (LIPUS) has been widely used for bone fracture healing. In this study, we examined the effects of LIPUS on bone mass after PTH withdrawal in ovariectomized (OVX) model mice. The LIPUS-non-irradiated femoral trabecular bone mineral density (BMD) in the treated after PTH withdrawal was significantly decreased. Meanwhile, the femoral BMD in the OVX + PTH-LIPUS group was remarkably higher than that of the OVX group. Additionally, mRNA expression of Runx2, Osterix, Col1a1, and ALP increased significantly following LIPUS irradiation after PTH withdrawal. These results suggest that LIPUS protected against femoral trabecular BMD loss and up-regulated the osteogenic factors following PTH withdrawal in OVX mice.

Efficacy and safety of tolvaptan in patients with malignant ascites: a phase 2, multicenter, open-label, dose-escalation study.

OBJECTIVE: This phase 2 study examined the efficacy and safety of tolvaptan, an aquaretic drug, in the treatment of ascites associated with cancer. METHODS: In the dose-escalation phase, oral tolvaptan was initiated at a dose of 3.75 mg/day, and the dose was increased daily to 7.5, 15 and 30 mg/day. Dose escalation was terminated once the increase from baseline in the daily urine volume reached 500 ml, at which point the patient proceeded to the maintenance phase of 5-7 days. Improvement of ascites was determined primarily by reduction in body weight and ascitic fluid volume. RESULTS: The mean change from baseline in body weight was maintained below 0 kg throughout the study. The mean change (±standard deviation) from baseline in ascitic fluid volume at the end of treatment (EOT) was 237.45 ± 868.14 ml in 33 evaluable patients. Although an increase from baseline in ascitic fluid volume at the EOT was observed in 23 of 33 patients (maximum: 1589.3 ml, minimum: 3.83 ml), a reduction in ascitic fluid volume was observed in the remaining 10 patients (maximum: -2304.3 ml, minimum: -27.5 ml). The common treatment-emergent adverse events included vomiting (5 of 43 patients, 11.6%), abdominal distension, constipation, thirst, blood osmolarity increased and renal impairment (3 of 43 patients, 7.0% each). CONCLUSIONS: Tolvaptan seemed to have no definitive effect on reducing ascites; however, it might be effective in at least some cancer patients. No new safety concerns were identified at doses of 3.75-30 mg/day.

Safety of switching to brexpiprazole in Japanese patients with schizophrenia: A post-hoc analysis of a long-term open-label study.

OBJECTIVES: To determine the long-term safety of switching to brexpiprazole from aripiprazole or non-aripiprazole dopamine antagonists. METHODS: Post-hoc analysis of 56-week study of Japanese outpatients with schizophrenia switched to brexpiprazole 2 mg/day over 4-week switching period with further titration (1-4 mg/day) allowed during the 52-week, open-label period. Major assessment items: total/low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol, triglycerides, blood glucose, body weight and prolactin. Secondary evaluations were related to efficacy, treatment emergent adverse events (TEAEs), extrapyramidal symptoms, and corrected QT interval (QTc). RESULTS: 84/186 (45.2%) patients (aripiprazole, 32.9%; non-aripiprazole, 54.8%) discontinued treatment over 56 weeks mainly because of consent withdrawal/adverse events. From baseline to Week 56, both groups showed minimal mean changes in total/LDL-/HDL-cholesterol, triglycerides, and glucose levels and a slight increase in mean (SD) body weight (aripiprazole, 1.1 [4.4] kg; non-aripiprazole, 0.4 [4.6] kg). Mean prolactin levels increased slightly in the aripiprazole group, but decreased in the non-aripiprazole group. Symptom severity scores decreased similarly in both groups. TEAEs occurred in 161/186 (86.6%) patients (aripiprazole, 84.1% [serious, 9.8%]; non-aripiprazole, 88.5% [serious, 14.4%]). Few changes occurred in extrapyramidal symptom scales or QTc interval. CONCLUSIONS: Switching to brexpiprazole is associated with a low long-term risk for metabolic abnormalities (including weight gain), hyperprolactinemia, extrapyramidal symptoms and QTc changes and minimal changes in psychiatric symptoms.

Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer.

The transcription factor Foxp3 is involved in the differentiation, function and survival of CD4+CD25+ regulatory T (T(reg)) cells. Details of the mechanism underlying the induction of Foxp3 expression remain unknown, because studies of the transcriptional regulation of the Foxp3 gene are limited by the small number of T(reg) cells in mononuclear cell populations. Here we have generated a model system for analyzing Foxp3 induction and, by using this system with primary T cells, we have identified an enhancer element in this gene. The transcription factors Smad3 and NFAT are required for activity of this Foxp3 enhancer, and both factors are essential for histone acetylation in the enhancer region and induction of Foxp3. These biochemical properties that define Foxp3 expression explain many of the effects of transforming growth factor-beta on the function of Foxp3+ T(reg) cells.

Eutectic Phenomenon of LiNH2-KH Composite in MH-NH3 Hydrogen Storage System.

Hydrogenation of a lithium-potassium (double-cation) amide (LiK(NH2)2), which is generated as a product by ammonolysis of litium hydride and potassium hydride (LiH-KH) composite, is investigated in details. As a result, lithium amide (LiNH2) and KH are generated after hydrogenation at 160 °C as an intermediate. It is noteworthy that the mixture of LiH and KNH2 has a much lower melting point than that of the individual melting points of LiNH2 and KH, which is recognized as a eutectic phenomenon. The hydrogenation temperature of LiNH2 in the mixture is found to be significantly lower than that of LiNH2 itself. This improvement of reactivity must be due to kinetic modification, induced by the enhanced atomic mobility due to the eutectic interaction.

Catalytic modification in dehydrogenation properties of KSiH3.

A number of known catalysts, which have been proven to be very effective for several hydrogen species, were studied in order to determine their effects on the hydrogen ab/desorption properties of KSiH3. Among all the catalysts used in this work, mesoporous Nb2O5 is found to be quite effective, with a reduction in activation energy from 142 kJ mol(-1) for pristine KSi to 63 kJ mol(-1) for mesoporous-Nb2O5-added KSi, thus allowing desorption to start at 100-120 °C. Any disproportionation is not observed in the controlled hydrogenation process. The mechanism for this improvement is also proposed in detail. The kinetic modifications on the ab/desorption properties of KSiH3 provide an alternative to the well-known family of heavy BCC alloys which are capable of working in the same temperature range but with a lower gravimetric hydrogen content, almost half of the KSi system.

A multicenter, single-arm, open-label interventional study of adherence to brexpiprazole during switching from previous antipsychotic drugs in patients with schizophrenia or schizoaffective disorder.

The rate of medication persistence was examined in patients with schizophrenia or schizoaffective disorder during switching from previously administered antipsychotics to brexpiprazole, a new dopamine D2 receptor partial agonist. A multicenter, single-arm, open-label 24-week interventional study was conducted, consisting of two 12-week consecutive periods: an initial switch (by plateau cross-titration) with the subsequent period, followed by a second maintenance period. Prior antipsychotics were olanzapine or risperidone/paliperidone. The primary and secondary outcome measures were medication persistence rates after the first 12 weeks and changes from baseline in the Specific Levels of Functioning Scale (SLOF), Subjective Well-being under Neuroleptic drug treatment Short form (SWNS), and Positive and Negative Syndrome Scale (PANSS) scores, respectively. In total, 79 patients were administered brexpiprazole and the medication persistence rate at 12 weeks was 78.5%, which was significantly higher than the predefined threshold of 65%. Regarding the prior medication, the persistence rate at 12 weeks was 84.6% for olanzapine and 72.5% for risperidone/paliperidone. Significant improvements from baseline were observed in the SLOF, SWNS, and PANSS scores. There were no adverse events of concern. Thus, brexpiprazole appeared to be a suitable antipsychotic on switching from olanzapine, risperidone, or paliperidone.

Cost Effectiveness of Fremanezumab in Episodic and Chronic Migraine Patients from a Japanese Healthcare Perspective.

BACKGROUND AND OBJECTIVES: Fremanezumab is an effective treatment for episodic (EM) and chronic migraine (CM) patients in Japan, but its cost effectiveness remains unknown. The objective of this study was to determine the cost effectiveness of fremanezumab compared with standard of care (SOC) in previously treated EM and CM patients from a Japanese healthcare perspective. METHODS: Estimated regression models were implemented in a probabilistic Markov model to inform effectiveness and health-related quality-of-life data for fremanezumab and SOC. The model was further populated with data from the literature. The adjusted Japanese healthcare perspective included productivity losses. The main model outcomes were quality-adjusted life-years (QALYs), costs (2022 Japanese Yen [¥]), and incremental outcomes including the incremental cost-effectiveness ratio (ICER). Analyses were performed separately for the EM and CM patients and combined. Costs and effects were discounted at an annual rate of 2.0%. RESULTS: The mean QALYs over a 25-year time horizon for the EM and CM populations combined were 13.03 for SOC and 13.15 for fremanezumab. The associated costs were ¥27,550,292 for SOC and ¥28,371,048 for fremanezumab. QALYs were higher and costs lower for EM patients compared with CM patients for both fremanezumab and SOC. The deterministic ICERs of fremanezumab versus SOC were ¥6,334,861 for EM, ¥7,393,824 for CM, and ¥6,530,398 for EM and CM combined. Indirect costs and choice of mean migraine days model distribution had a substantial impact on the ICER. CONCLUSION: Using fremanezumab in a heterogeneous mixture of Japanese EM and CM patients resulted in a reduction of monthly migraine days and thus more QALYs compared with SOC. The cost effectiveness of fremanezumab versus SOC in EM and CM patients resulted in an ICER of ¥6,530,398, from an adjusted Japanese public healthcare perspective.

Fremanezumab is an effective treatment for episodic and chronic migraine patients in Japan, but it is unknown how the costs relate to the health benefits. The current research determined the relation between costs and effects of fremanezumab compared with the current standard of care in Japanese clinical practice, to see if the costs are justified by the health benefits. A model was used to inform the treatment effect of fremanezumab and standard of care. Data on costs, the frequency in which health care was used, and impairment of work due to migraine were also included in the model and obtained from the literature. The main outcomes were the number of years that patients were alive while taking their quality of life into account, costs, and the difference in these outcomes between patients who were treated with fremanezumab and those receiving standard of care. Subsequently, it was estimated how costs and effects related to one another and whether the costs were justified by the health benefits. The outcomes showed that patients treated with fremanezumab had a better quality of life compared with those receiving standard of care, while the costs associated with fremanezumab were higher. Compared with standard of care, the health benefits of treating patients with fremanezumab were justified by the costs within an acceptable range. Taking the absence from work due to illness into account had a substantial impact on the model outcomes.

Low-intensity pulsed ultrasound irradiation attenuates collagen degradation of articular cartilage in early osteoarthritis-like model mice.

PURPOSE: Osteoarthritis (OA) is a combination of degeneration and destruction of articular cartilage due to mechanical stress, secondary synovitis, and bone remodelling. In recent years, early knee OA, a preliminary stage of structural failure in OA, has attracted attention as a potential target for therapy to prevent the onset of OA. Intra-articular administration of monoiodoacetic acid (MIA) induces OA-like symptoms, and low doses of MIA induce early OA like symptoms. In this experiment, a low-dose of MIA was induced to early OA model mice, which were then irradiated with low-intensity pulsed ultrasound (LIPUS) to examine whether LIPUS improves symptoms of early OA. METHODS: After 4 weeks of LIPUS irradiation, articular cartilage was observed at 1 and 4 weeks. The Osteoarthritis Research Society International (OARSI) scores were calculated using Safranin-O staining results. Cartilage degeneration was detected using Denatured Collagen Detection Reagent (DCDR). RESULTS: We observed a significant decrease in OARSI scores in the LIPUS irradiated group at week 4. The non-LIPUS group showed widespread areas of double positivity for Type II collagen and DCDR, whereas the LIPUS group showed only a small number of DCDR-positive areas. In addition, macrophage numbers counted in the articular capsule at week 1 showed a significant decrease in the LIPUS irradiated group. Lubricin detection showed that lubricin positive cell number was significantly increased by LIPUS irradiation at week 4. CONCLUSIONS: These results suggest that LIPUS attenuates cartilage degeneration in early OA by relieving inflammation and enhancing the inhibitory effect of lubricin on cartilage degeneration.

Trace Ammonia Equilibrium Pressure of Zirconium Phosphate in Moisture.

Zirconium phosphate-absorbed ammonia gas and the ammonia concentration (pressure) decreased to 2 ppm (ca. 20 Pa). However, it has not been clarified what the equilibrium pressure of zirconium phosphate is during ammonia gas ab/desorption. In this study, the equilibrium pressure of zirconium phosphate during ammonia ab/desorption was measured using cavity ring-down spectroscopy (CRDS). For ammonia-absorbed zirconium phosphate, a two-step equilibrium plateau pressure was observed during the ammonia desorption in gas. The value of the higher equilibrium plateau pressure at the desorption process was about 25 mPa at room temperature. If the standard entropy change (ΔS0) of the desorption process is assumed to be equal to the standard molar entropy of ammonia gas (192.77 J/mol(NH3)/K), the standard enthalpy change (ΔH0) is about -95 kJ/mol(NH3). In addition, we observed hysteresis in zirconium phosphate at different equilibrium pressures during ammonia desorption and absorption. Finally, the CRDS system allows the ammonia equilibrium pressure of a material in the presence of water vapor equilibrium pressure, which cannot be measured by the Sievert-type method.

Modeling Monthly Migraine-Day Distributions Using Longitudinal Regression Models and Linking Quality of Life to Inform Cost-Effectiveness Analysis: A Case Study of Fremanezumab in Japanese-Korean Migraine Patients.

BACKGROUND AND OBJECTIVES: As regression approaches have been used more recently to model the effectiveness and health-related quality of life (HRQOL) of novel migraine treatments, an example is provided for fremanezumab. The objective is to estimate the distribution of mean monthly migraine days (MMD) as a continuous variable and corresponding migraine-specific utility values as a function of the MMD, to inform health states in a cost-effectiveness model (CEM). METHODS: Three longitudinal regression models (zero-adjusted gamma [ZAGA], zero-inflated beta-binomial [ZIBB], and zero-inflated negative binomial [ZINBI]) were fitted to Japanese-Korean clinical trial data of episodic (EM) and chronic migraine (CM) patients treated with fremanezumab or placebo, to estimate MMD over a period of 12 months. The EQ-5D-5L and the migraine-specific quality-of-life (MSQ), mapped to the EQ-5D-3L, questionnaires were used to measure HRQOL. Migraine-specific utility values were estimated as a function of MMD using a linear mixed effects model. RESULTS: The ZIBB models fitted the data best in estimating the distribution of mean MMD over time. MSQ-derived values were more sensitive than the EQ-5D-5L values for the effect of the number of MMD on HRQOL, with higher values for less MMD and more time on treatment. CONCLUSIONS: Using longitudinal regression models to estimate MMD distributions and linking utility values as a function is an appropriate method to inform CEMs and capture inter-patient heterogeneity. The observed distribution shifts demonstrated fremanezumab's effect at reducing MMD for both EM and CM patients, while treatment effect on HRQOL was captured by MMD and time on treatment.

The current study provides an example of an approach that can be used to estimate the number of migraine days per month and the quality of life of migraine patients. The outcomes of this approach can give an impression of how well a patient reacts to a new migraine treatment called fremanezumab. In this study, different mathematical equations were used to measure the migraine days per month and quality of life over a period of 1 year. The data came from Japanese-Korean patients that participated in clinical trials. The patients reported the number of days that they had migraine and their quality of life was measured with two validated questionnaires. With the gathered data, the quality of life was calculated for the number of migraine days that a patient could have per month. Patients who had the fewest migraine days and were treated the longest with the new treatment reported the best quality of life. The investigated approach is an appropriate method to measure the impact of fremanezumab on the number of monthly migraine days and a patient's quality of life. The measurements of this approach can be linked to other parameters in an economic model to estimate the costs required to reach a certain level of treatment effect with this new migraine treatment.

Regeneration Process of Ammonia-Absorbed Zirconium Phosphate to Zirconium Phosphate.

Zirconium phosphate [Zr(HPO4)2·H2O] absorbs 2 mol(NH3)/mol[Zr(HPO4)2·H2O] with a low equilibrium plateau ammonia concentration of around 1 ppm in water. In this study, in order to investigate the regeneration process of ammonia-absorbed zirconium phosphate [Zr(NH4PO4)2·H2O], Zr(NH4PO4)2·H2O was heat-treated above 353 K under an inert gas. Then, the structures of the heat-treated samples were evaluated using powder X-ray diffraction and thermogravimetry-mass spectrometry measurements. Zr(NH4PO4)2·H2O started to desorb ammonia and the crystal water at 353 K. Then, Zr(NH4PO4)2·H2O was changed to the anhydrous monoammoniate [Zr(NH4PO4)(HPO4)] at 473 K and formed anhydrous zirconium phosphate [Zr(HPO4)2] at 673 K. The anhydrous zirconium phosphate and the anhydrous monoammoniate reabsorbed ammonia in ammonia water. Those initial absorption rates were small compared with Zr(HPO4)2·H2O. The slow kinetics of the anhydrous zirconium phosphate corresponded to the small interlayer distances. The ammonia concentration composition isotherms indicated that the anhydrous zirconium phosphate and anhydrous monoammoniate have a low ammonia equilibrium plateau concentration of around 1 ppm in ammonia water. Zr(NH4PO4)2·H2O is formed from Zr(NH4PO4)(HPO4) by the reabsorption of ammonia and water after 1-10 cycles. We found that zirconium phosphate is an ammonia remover which can be used repeatedly at 473 K.

Anomalous large capacitances of porous carbons based on protium adsorption.

The capacitances of porous carbon anodes were determined using a Ni(OH)2 cathode. We found that the capacitances were 300-700 F g-1 and above 3 times those of the carbon anodes prepared by electrical double layer formation, revealing the large capacitances based on protium H adsorption in the presence of highly concentrated KOH solution.

Crystal structure and dynamics of Mg(ND3)6Cl2.

The crystal structure and dynamics of Mg(ND(3))(6)Cl(2) have been investigated by powder neutron diffraction and molecular dynamics. The powder diffraction data can be well described by 4 partly occupied deuterium sites in a square arrangement around the N atoms, which is seemingly inconsistent with the 3-fold symmetry of the ND(3) molecule. Molecular dynamics show highly correlated rotational and translational motion of the ND(3) molecules which explains the apparent 4-fold symmetry of the deuterium arrangement. A more disordered structure model based on the molecular dynamics results gives a better fit to the experimental data and is in agreement with the 3-fold symmetry of ND(3).

Entropy differences between hydrides and other elements.

The standard entropy differences between hydrides and other elements (metals, liquid N2, toluene) ΔS were increased with the volume differences ΔV. It was found that ΔS is roughly expressed by the following equation, |ΔS|∝Rln|ΔV|, in which R is the gas constant.

Temperature rise of LaNi5-based alloys by hydrogen adsorption.

The temperature rise of AB5-type alloys by hydrogen adsorption was limited by their critical temperatures (Tc). We found the relation between the H2 desorption temperatures of metal hydrides at atmospheric pressure (Ts) and their Tc followed the Guldberg rule (Tc = 3/2 Ts), revealing a simple method to estimate Tc.

Real-World Treatment Patterns and Adherence to Oral Medication Among Patients with Bipolar Disorders: A Retrospective, Observational Study Using a Healthcare Claims Database.

PURPOSE: This study aimed to describe real-world treatment patterns and medication adherence among patients with bipolar disorder (BD) in Japan. PATIENTS AND METHODS: Adult patients with a BD diagnosis were identified between July 2013 and February 2018, using an employment-based health insurance claims database from the JMDC Inc. Treatment patterns of target drugs (mood stabilizers, antipsychotics) and adherence (measured by the proportion of days covered [PDC]) were assessed during the first- through third-year follow-up. Adherence was also assessed for patient subgroups. RESULTS: The analyzed population included 13,788 patients with BD. They were mostly prescribed sodium valproate, lithium, or aripiprazole (range: 21.1-27.4%) across 3 years of follow-up, whereas lamotrigine was prescribed to 11.2-12.8% of patients. Benzodiazepines (70-87%) and antidepressants (52-71%) were commonly prescribed during all three follow-up periods. The mean PDC among all patients with BD was 0.51 during the first and increased to 0.61 during the third year. The mean PDC was 0.42 (first year) in patients aged <30 years and 0.49 in those aged 30-40 years. The PDC was 0.44-0.61 (depending on the drug class) in those who were prescribed a single-class target drug and 0.68-0.83 in those prescribed two drug classes concomitantly. CONCLUSION: This study documented generally low medication adherence among patients with BD, and those at young age. These patients may require more attention.

Synergetic NH3 absorption properties of the NaBH4-LiBH4 mixed system.

NaBH4 does not absorb NH3 below 100 kPa but transforms into a liquid state after NH3 absorption. On the other hand, LiBH4 absorbs NH3 at pressures lower than 100 kPa. Interestingly, mixed borohydrides absorbed NH3 at low pressures and were liquefied above 100 kPa due to a synergetic phenomenon. The kinematic viscosity of the liquefied state was in situ analyzed during NH3 absorption.

Clinical characteristics of patients with alcohol dependence comorbid with hypertension among regular drinkers: An internet-based, cross-sectional study in Japan.

While evidence suggests a strong association between alcohol and hypertension, little is known about the profile of patients with alcohol dependence comorbid with hypertension. This study aimed to clarify the clinical characteristics and health problems of this population through a web-based questionnaire survey using a research company's panel of adults in Japan. Of 20 000 regular drinkers, 176 on treatment for hypertension and with alcohol dependence (confirmed and/or an Alcohol Use Disorders Identification Test score ≥15 points) were included. Participants were asked about their health-related quality of life, work productivity, blood pressure (BP) control, receipt of brief interventions, and awareness of their alcohol dependence. Results were compared between the BP-controlled and BP-uncontrolled groups. The mean EQ-5D utility score was 0.838 in the entire population, and 0.786 vs. 0.892 in the groups (p < 0.0001). When 133 'employed' participants were compared, productivity loss was more apparent in the BP-uncontrolled group (presenteeism, 27.3% vs. 6.1%, p < 0.0001; absenteeism, 10.7% vs. 1.0%, p = 0.0003). The rate of dissatisfaction with BP control was 55.1% in the entire population (most [76.3%] of those dissatisfied considered alcohol a cause of inadequate BP control), ~78% in the uncontrolled group, and ~34% in the controlled group. Of those previously advised to reduce drinking or abstain from alcohol (60.2% of all participants), 63% (BP-uncontrolled group) and 55% (BP-controlled group) decreased their drinking. Though more than twice as many participants thought themselves to be alcohol-dependent in the BP-uncontrolled group than in the controlled group (41% vs. 15%), most (59% vs. 85%) showed no self-awareness of alcohol dependence. Patients with alcohol dependence comorbid with hypertension had impaired health status and reduced work productivity. They thought alcohol was the most common cause of inadequate BP control. Treatment beyond brief interventions is needed to enhance their awareness of alcohol dependence and their motivation to reduce drinking.

Post-hoc analysis investigating the safety and efficacy of brexpiprazole in Japanese patients with schizophrenia who were switched from other antipsychotics in a long-term study (Secondary Publication).

A post hoc analysis was performed using data obtained over eight weeks from 200 Japanese patients with schizophrenia who were switched to brexpiprazole monotherapy in a long-term treatment study. The 8-week period comprised of a 4-week switching phase and a 4-week post-switch phase. For the antipsychotic switching schedule, brexpiprazole was first administered at 1 mg/day and increased to 2 mg/day by the end of week 4. Concurrently, the previous antipsychotic(s) was/were tapered gradually from the start of week 3 and discontinued by the end of week 4. Brexpiprazole could then be increased up to 4 mg/day according to the CGI-I criteria. At week 8, 1.8%, 23.2%, 25.0%, and 50% of patients were administered daily brexpiprazole doses of 1, 2, 3, and 4 mg, respectively. The discontinuation rate at week 8 was 17.0%. The major reasons for discontinuation were consent withdrawal (9.5%), occurrence of adverse events (5.5%), and physician's decision (2.0%). Commonly reported adverse events were nasopharyngitis (13.5%), schizophrenia (9.0%), insomnia (6.5%), headache (5.5%), and akathisia (5.5%). The discontinuation rate was 4.9% for patients who were switched from aripiprazole as the primary antipsychotic and 25.4% for those who were switched from other antipsychotics. Owing to the serious adverse events that led to treatment discontinuation, careful switching to brexpiprazole is necessary in patients who previously used olanzapine as their primary antipsychotic.