山田 成樹

IMPORTANCE: Hyponatremia is an adverse event associated with antipsychotic use; however, comparative evidence among individual second-generation antipsychotics remains limited. OBJECTIVE: To compare the risk of hyponatremia associated with individual second-generation antipsychotics. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study and disproportionality analysis, data were obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS; quarter 4 1997 to quarter 3 2023), a dataset provided by the Japan Pharmaceutical Information Center, and a Japanese hospital-based claims database (Medical Data Vision; April 2008 to April 2024). The study adopted a new-user design and included patients routinely prescribed antipsychotics. Patients aged 18 to 69 years with at least 180 days of active medical history preceding the initial antipsychotic prescription, with no history of antipsychotics or hyponatremia during that period, were included. EXPOSURES: Initiation of second-generation antipsychotics. MAIN OUTCOMES AND MEASURES: Hyponatremia associated with individual antipsychotics was compared with that associated with olanzapine. Reporting odds ratios with 95% CIs were calculated for FAERS. The incidence within 180 days of treatment initiation was analyzed for claims database using hazard ratios estimated with stabilized inverse probability of treatment weighting based on propensity scores. RESULTS: In the FAERS database, most antipsychotics showed lower reporting odds ratios for hyponatremia than olanzapine. In a Japanese claims database, among 961 010 patients prescribed antipsychotics, 55 394 were included in the final analysis. The mean (SD) age was 50.4 (14.3) years, and there were 25 839 (46.6%) male and 29 555 (53.4%) female patients. After stabilized inverse probability of treatment weighting, aripiprazole was associated with a significantly lower risk of hyponatremia than olanzapine (adjusted hazard ratio, 0.52; 95% CI, 0.35-0.76), whereas other antipsychotics showed no significant differences. Sensitivity analysis confirmed the robustness of the findings. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of antipsychotic users, aripiprazole was associated with a lower risk of hyponatremia than was olanzapine. Although residual confounding should be considered, these findings may help inform clinical decision-making for high-risk patients.

AIM: To identify specific pharmacists' practices associated with participation in multidisciplinary team conferences and meetings such as pre-visit conferences, predischarge conferences, and care planning meetings in Japanese home-based care. METHODS: An online survey was conducted for community pharmacists involved in home-based care across Japan in 2023. We compared the implementation of daily pharmacists' practices between those who participated in multidisciplinary team conferences and meetings and those who did not. Multivariable logistic regression analysis was conducted to evaluate the associations of individual pharmacists' practices with participation in multidisciplinary team conferences and meetings. RESULTS: This study included 1151 community pharmacists, with 676 pharmacists (59%) participating in multidisciplinary team conferences and meetings. Daily practice associated with participation in these conferences and meetings included collecting information on how to store and set medications (adjusted odds ratio [aOR], 1.86; 95% confidence interval [CI], 1.34-2.59), confirmation of medication intake (aOR, 1.42; 95% CI, 1.06-1.91), and gathering information on medication prescribed at other medical institutions (aOR, 1.89; 95% CI, 1.42-2.51). CONCLUSION: We identified some daily practices, including collecting medication management information, gathering all prescription details, and confirming medication intake, which were associated with participation in multidisciplinary team conferences for community pharmacists. Facilitating these practices could further enhance interprofessional collaboration, facilitate the standardization of home-based pharmaceutical care practices, and inform the optimization of future medical fees to ensure high-quality patient support.

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.

BACKGROUND: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear. OBJECTIVES: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles. DESIGN: A pharmacovigilance-pharmacodynamic analysis using a spontaneous reporting system. METHODS: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug-drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the Ω shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models. RESULTS: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D4 receptor occupancy and the point estimates of signal values was observed in the Ω shrinkage measure model (β = 0.295, 95% confidence interval: 0.119-0.471, p = 0.002) and replicated across all frequency statistical models. CONCLUSIONS: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings.

AIMS: Polypharmacy, hyperpolypharmacy, and potentially inappropriate medication (PIM) in older adults are growing health concerns in the aging population. Older patients with degenerative cervical myelopathy (DCM) often have multiple comorbidities and are prescribed numerous medications. Thus, we investigated the current status of medication use among older patients with DCM, identified the characteristics of those with hyperpolypharmacy, and evaluated its impact on postoperative outcomes. METHODS: This retrospective study included 130 older patients with surgery for DCM. All participants completed the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) before and 1 year after surgery. RESULTS: Forty-two patients had hyperpolypharmacy (H group), and 88 had non-hyperpolypharmacy (N group). The commonly prescribed PIMs were antidiabetics (24.6%), nonsteroidal anti-inflammatory drugs (21.5%), and hypnotics (20.8%). Hypnotic use was significantly higher in the H group than in the N group (p < 0.001). The H group exhibited significantly more advanced frailty than the N group (p = 0.001). The preoperative JOACMEQ scores for upper extremity, lower extremity, and bladder function were significantly worse in the H group than in the N group (p = 0.020, 0.003, and 0.007, respectively) and remained significant following the multivariable model. Both groups had favorable surgical outcomes, but quality of life improvements were significant in the N group (p = 0.005) but not in the H group (p = 0.900). CONCLUSIONS: Older DCM patients with hyperpolypharmacy had more severe preoperative symptoms. Although surgery is a viable treatment option for this population, thorough preoperative informed consent regarding surgical outcomes is critically important.