Clinical Laboratory Data in Japan: A Comparative Study of Patients with Psychiatric Disorders and the General Population.

Purpose: Several nationwide population-based studies have reported that patients with psychiatric disorders are at higher risk of developing chronic kidney disease, chronic liver disease, and metabolic syndrome than the general population; however, there are insufficient studies in the Japanese population. Thus, we aimed to clarify the influence of psychiatric disorders on clinical laboratory data in the Japanese population. Patients and Methods: This cross-sectional study was based on medical records from the Department of Psychiatry at Fujita Health University Hospital and the 6th National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data Japan (specific health checkups in 2018) in the Ministry of Health, Labor and Welfare. The primary endpoint was the incidence of clinical laboratory abnormalities in patients with psychiatric disorders and the general Japanese population. Results: Compared to the general Japanese population, patients with psychiatric disorders had significantly higher rates of the following clinical laboratory abnormalities: estimated glomerular filtration rate, alanine transaminase, aspartate aminotransferase (AST), body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), triglycerides, and hemoglobin A1c (HbA1c). In the age-specific analysis, AST, BMI, HDL-C, and HbA1c levels were more frequently abnormal in patients with psychiatric disorders only in the 40-49 and 50-59 age groups. Conclusion: Our results showed that patients with psychiatric disorders have higher rates of various clinical laboratory abnormalities than the general Japanese population, with stronger influences in the middle-aged group. These data suggest the importance of monitoring and preventing chronic diseases in patients with psychiatric disorders in Japan.

Analysis of clozapine-induced seizures using the Japanese Adverse Drug Event Report database.

Among antipsychotics, clozapine is associated with a high risk of seizures. This study aimed to generate novel hypotheses regarding trends in the onset of clozapine-induced seizures using the JADER (Japanese Adverse Drug Event Report) database. Seizures were defined according to the Standardized MedDRA Queries (SMQ) for convulsions (SMQ20000079). Trends in the onset of clozapine-induced seizures were assessed using multivariate logistic regression analysis with covariates of sex, age, clozapine dose, antipsychotic polypharmacy, concomitant medications, and history of convulsive disorder. In addition, we assessed the time-to-onset of clozapine-induced seizures using the median time, interquartile range, and Weibull shape parameter. The JADER database registered 2,745 cases of adverse events with clozapine, and 1,784 cases were included in the analysis after excluding cases for which clinical information was not available. Medium (200-400 mg) and high (> 400 mg) doses of clozapine had a significantly higher reporting rate of seizures than low doses (< 200 mg) (adjusted reporting odds ratio [aROR] = 3.05, 95% confidence interval [CI]: 1.86-4.99 and aROR = 9.81, 95% CI: 6.06-15.89, respectively). Younger age, antipsychotic polypharmacy, and concomitant use of lithium were also significantly associated with reports of seizures. The time-to-onset analysis of 222 cases of clozapine-induced seizures showed that the median time was 134 (interquartile range, 72-295) days. The 95% CI of the WSP ß-value for clozapine-induced seizures included 1 and was classified as a random failure type. In conclusion, the results suggest that clozapine-induced seizures are dose-dependent adverse events that should be monitored with consideration of the effects of age and concomitant medications. Further epidemiological research is needed to strengthen and validate our hypotheses.

Effectiveness of Clozapine on Employment Outcomes in Treatment-Resistant Schizophrenia: A Retrospective Bidirectional Mirror-Image Study.

Purpose: Clozapine is more effective than other antipsychotics and is the only antipsychotic approved for treatment-resistant schizophrenia. The objective of this study is to reveal the effect of clozapine on employment using a bidirectional mirror-image model. Patients and Methods: This design was a retrospective observational study that investigated the employment status of patients with treatment-resistant schizophrenia based on medical records. The bidirectional mirror-image model consisted of 1) switching from other antipsychotics to clozapine and 2) switching from clozapine to other antipsychotics. The observation period was 1 year for each pre- and post-clozapine initiation and discontinuation. Results: We included 36 patients in the bidirectional mirror-image model. The regular employment plus employment support rate was significantly higher in the clozapine phase than in the other antipsychotic phase in the bidirectional mirror-image model (30.6% vs 11.1%, P = 0.039). The days of regular employment plus employment support were also significantly longer in the clozapine phase (61.3 ± 106.2 vs 24.7 ± 82.7 days, P = 0.032). As per the unidirectional mirror-image model, switching to clozapine resulted in significantly higher regular employment plus employment support rates in the clozapine phase than those in the other antipsychotic phase (33.3% vs 10.0%, P = 0.039). Switching from clozapine to other antipsychotics did not exhibit significant differences in any outcomes. Conclusion: The results suggest that clozapine is superior to other antipsychotics with respect to achieving employment in patients with treatment-resistant schizophrenia. However, biases specific to the mirror-image model need to be considered.

Efficacy of a Pharmacist Team Clinical Medication Review in Older Adults: A Prospective and Retrospective Observational Study.

Polypharmacy in older adults causes problems such as increased adverse drug reactions, overdose or duplication, and poor medication adherence. We have established a "medication review team" organized by pharmacists. This prospective and retrospective observational study evaluated the effectiveness of the pharmacist-led team-based approach for reducing polypharmacy as compared to the individual pharmacist approach. Data on the individual pharmacist approach were collected retrospectively, but prospectively for the pharmacist-led team approach. The study included patients who were admitted to the nephrology, orthopedic surgery, and psychiatry wards. Characteristics for patient included in each study group were adjusted using the propensity score method. The pharmacist-led team approach had a significantly higher medication change rate compared to that of the individual pharmacist approach (odds ratio (OR), 2.28; 95% confidence interval (CI), 1.21 to 4.46; p = 0.009). The rate of patients with two or more medication discontinuations and the rate of patients with intervention by young clinical pharmacist were also significantly higher in the pharmacist-led team approach (OR, 2.19; 95% CI, 1.06 to 4.74; p = 0.03 and OR, 5.67; 95% CI, 1.22 to 53.15; p = 0.02, respectively). The rate of patients with discontinuation of potentially inappropriate medications was not significantly different between the two groups (OR, 2.07; 95% CI, 0.86 to 5.33; p = 0.11). Our results suggest that it is possible to improve the quality of medication review by conducting team conferences even with only pharmacists.

Treatment Continuation of Asenapine or Olanzapine in Japanese Schizophrenia Patients: A Propensity Score Matched Study.

OBJECTIVE: Asenapine is a second-generation antipsychotic agent that is classified as a multi-acting receptor-targeted antipsychotic and is similar to olanzapine. Our study aimed to compare the treatment continuation rate and reason for discontinuation of asenapine or olanzapine in schizophrenia using real-world data. METHODS: This design was a retrospective study. The primary endpoint was Kaplan-Meier estimates of the continuation rate at six months, with the propensity score method applied to adjust for potential confounders. RESULTS: A total of 95 patients were analyzed in this study (asenapine, n = 46; olanzapine, n = 49). Matched data were adjusted to consider six covariates (age, sex, chlorpromazine equivalent, diazepam equivalent, history of clozapine use, and history of modified electro convulsive therapy). The continuation rate at six months was 27.3% (95% CI, 15.6-47.6) in the asenapine group and 50.8% (95% CI, 34.3-75.3) in the olanzapine group (hazard ratio, 0.41; 95% CI, 0.21-0.82; P = 0.0088 by the Log rank test) in matched data. Cases of discontinuation because of the lack of efficacy were almost as frequent for asenapine (13.0%) as for olanzapine (10.2%). Discontinuation due to bitter taste (6.5%) and burden of the dosing method (6.5%) were observed only with asenapine, whereas anticholinergic side effects such as dry mouth (4.1%) and constipation (2.0%) were observed only with olanzapine. CONCLUSION: The low continuation rate of asenapine in real-world data may be related to specific factors such as bitter taste and burden of the dosing method.

Assessment of Switching to Suvorexant versus the Use of Add-on Suvorexant in Combination with Benzodiazepine Receptor Agonists in Insomnia Patients: A Retrospective Study.

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.

Influence of serum albumin levels during opioid rotation from morphine or oxycodone to fentanyl for cancer pain.

Morphine, oxycodone, and fentanyl are commonly used to control cancer pain. Because these drugs have differences in receptor affinity or pharmacokinetic parameters, changing the opioid formulation may result in an unexpected outcome, depending on the patient's condition. This study investigated whether low serum protein levels influence the effectiveness of opioid rotation by determining the impact of serum albumin levels on the analgesic effect before and after opioid rotation from morphine or oxycodone to fentanyl in cancer patients. The patients were classified into 3 groups according to their serum albumin levels before opioid rotation: group 1, <2.5 g/dL; group 2, from 2.5 g/dL to <3.0 g/dL; and group 3, ≥3.0 g/dL. There was no significant change in the percentage of patients with good pain control after rotation in group 1 or group 2; however, the percentage of patients with good pain control increased significantly in group 3. When the percentage of patients whose numerical rating scale scores increased, were unchanged, or decreased after rotation were compared, a significant difference in the percentage of those showing improvement was noted among the 3 groups and between groups 1 and 3. These findings suggest that monitoring serum albumin levels during fentanyl therapy is useful for pain management, and that the effectiveness of opioid rotation to fentanyl in patients with serum albumin levels of <2.5 g/dL should be carefully evaluated after rotation.