Objective: This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). Results: A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate.However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemiaew onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis. Conclusion Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.

OBJECTIVE: Suvorexant is a novel hypnotic drug that does not interact with the conventional γ-aminobutyric acid (GABA)-A receptor. We investigated the method by which suvorexant was introduced in insomnia patients who were taking benzodiazepine receptor agonists (BzRA). METHODS: This was a retrospective study. We extracted clinical data for patients who were prescribed suvorexant and were already using BzRA. The patients were assigned to two groups, the switching and add-on groups. We assessed the suvorexant discontinuation rate at one month after the prescription of the drug. RESULTS: One hundred and nineteen patients were assigned to the switching group, and 109 were assigned to the add-on group. The add-on group exhibited a significantly higher all-cause discontinuation rate than the switching group (odds ratio, 2.7; 95% confidence interval, 1.5 to 5.0; adjusted p < 0.001). Intolerability was a significantly stronger risk factor for suvorexant discontinuation in the add-on group (22.0% vs. 7.6%, p < 0.002), and the most common adverse effect was oversedation. CONCLUSION: Our results show that the add-on of suvorexant increases the frequency of oversedation compared with switching in insomnia patients that are taking BzRA. However, this was only a preliminary retrospective study, and further studies will be required to confirm our findings.
Benzodiazepines* ; Humans ; Methods ; Orexin Receptor Antagonists ; Prescriptions ; Receptors, GABA-A* ; Retrospective Studies* ; Risk Factors ; Sleep Initiation and Maintenance Disorders*

In Japan, drug therapy for schizophrenia is characterized by high-dose antipsychotic polypharmacy, which is an uncommon approach internationally. In this study, we reduced the number of antipsychotic agents in 5 patients using the Safety Correction of High-dose Antipsychotic Polypharmacy (SCAP) method and conducted a survey regarding treatment satisfaction. The switch from polypharmacy to monotherapy was achieved in all patients. There was no deterioration in psychiatric symptoms, and adverse reactions were reduced. Three of the subjects were satisfied with the decrease in the number of antipsychotic agents and dose-reduction. These results suggest that the SCAP method is a safe and useful method that can be applied in a clinical setting.

Methods: The study included patients with ASD aged >60 years who underwent spinal corrective fusion surgery from the lower thoracic spine to the pelvis. The intraoperative PS insertion torque was measured using a torque meter. Pearson correlation coefficients were calculated between the PS insertion torque and the BMD, HU, and VBQ score. Preoperative bone quality was compared between the proximal junctional failure (PJF) and non-PJF groups. Results: Thirty-one patients with 177 PS at T10, T11, and T12 were analyzed. The PS insertion torque showed a moderate positive correlation with lumbar spine BMD (r=0.59–0.69, p<0.01), total hip BMD (0.58–0.62, p<0.01), and HU value (r=0.58–0.66, p<0.01). However, the VBQ score did not show significant correlation (r=−0.28 to −0.23, p >0.05). Notably, a strong correlation was found between the PS insertion torque and the HU value for screws of the same size (r=0.71 and 0.74, p<0.01). The HU value at T12 and the PS insertion torque at T10 were significantly lower in the PJF group than in the non-PJF group. Conclusions This study demonstrates a positive correlation between the PS insertion torque and HU value in the lower thoracic spine and a moderate correlation with BMD but not the VBQ score. Preoperative assessment using DEXA and CT is crucial for optimizing bone health management in ASD surgery.

OBJECTIVE: The adverse effects of antipsychotic agents can have a marked influence on medication adherence. In this study, we investigated the adverse events of antipsychotics that are less likely to be reported by patients and the reasons why such symptoms remain latent. METHODS: Data were collected by interviewing patients using a subjective questionnaire, and the associations between unreported symptoms and background factors were investigated. RESULTS: A total of 306 patients with schizophrenia or schizoaffective disorder were examined. Their major symptoms were daytime sleepiness (50.0%), weight gain (42.2%), and sexual dysfunction (38.9%). Sexual dysfunction was nominal significantly more common among the patients that had been treated with antipsychotic agent polypharmacy (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.07 to 4.30), and was nominal significantly more common among outpatients (OR, 1.78; 95% CI, 1.02 to 3.13). Only approximately 30% of the patients had reported their symptoms to their physicians. CONCLUSION: Patients receiving antipsychotic treatment tolerate some symptoms and do not feel able to report them to their physicians. The most common reason for this is an insufficient patient-physician relationship. Sexual dysfunction is especially hard to identify because it is a delicate problem, and our findings demonstrate that subjective questionnaires are helpful for detecting such symptoms.
Antipsychotic Agents ; Asian Continental Ancestry Group* ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Medication Adherence ; Outpatients ; Polypharmacy ; Psychotic Disorders ; Schizophrenia* ; Surveys and Questionnaires ; Weight Gain

Objective: To identify factors affecting adherence to medication, a subjective questionnaire survey was administered to schizophrenia patients regarding the prescribed antipsychotic formulations. Methods: We evaluated the patients’ satisfaction and dissatisfaction with prescribed antipsychotic formulations, and patients answered the Drug Attitude Inventory-10 Questionnaire (DAI-10). Inclusion criteria for patients are as follows:age between 20 and 75 years and taking antipsychotic agents containing the same ingredients and formulations, for at least 1 month. Results: In total, 301 patients answered the questionnaire survey. Tablets were found to be the most commonly used antipsychotic formulations among schizophrenia patients (n = 174, 57.8%), followed by long-acting injections (LAIs, n = 93, 30.9%). No significant differences in the formulation satisfaction level and DAI-10 scores were observed between all formulations. Formulations, except for LAI, were selected by physicians in more than half of the patients.Patients who answered “Decided by consultation with physicians” had significantly higher satisfaction levels and DAI-10 scores compared to those who answered “Decided by physicians” (4.11 ± 0.77 vs. 3.80 ± 1.00, p = 0.0073 and 6.20 ± 3.51 vs. 4.39 ± 4.56, p ＜ 0.001, respectively). Satisfaction levels moderately correlated with DAI-10 scores (r = 0.48, p ＜ 0.001). Conclusion No formulation had a high satisfaction level in all patients, and it is important to be reflect the patients’ individual preferences in pharmacotherapy. Shared decision-making in the selection of the formulations is seen to be useful for improving medication adherence.

Objective: To improve poor medication adherence in schizophrenic patients, long-acting injectable (LAI) antipsychotics are used. However, it has not yet become common in Japan. Recently, aripiprazole LAI was approved for alternative injection into the deltoid muscle in addition to the gluteal muscle. The acceptance for the proposal to switch from gluteal to deltoid injections of aripiprazole LAI was investigated. Methods: The subjects were 32 outpatients with schizophrenia who had continuously received aripiprazole LAI administration into the gluteal muscle for ≥ 6 months. In the patients who had continued deltoid injection for 3 months after switching, the changes in the pain and shame in comparison with gluteal injections were evaluated. Results: Switching to the deltoid injection was chosen by 17 out of 32 patients. Three months later, 9 patients were still receiving deltoid injections with highly rated satisfaction. The main reasons for switching to deltoid injections included the pain and shame associated with gluteal injections. The main reason for returning to the gluteal injection was the pain experienced from the injection in the deltoid. Conclusion The option to select the injected area was based on the amount of pain in the deltoid and gluteal sites, leading to the widespread use of aripiprazole LAI.