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"Azekawa, Takaharu"
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Real-world clinical predictors of manic/hypomanic episodes among outpatients with bipolar disorder
2021
Bipolar disorder is a mental illness in which manic and depressive states are repeated, causing psychosocial dysfunction. Manic/hypomanic episodes cause problems with interpersonal, social and financial activities, but there is limited evidence regarding the predictors of manic/hypomanic episodes in real-world clinical practice.
The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was administered in an observational study that was conducted to accumulate evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics by conducting a retrospective medical record survey. Our study extracted baseline patient characteristics from September to October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. We investigated the presence or absence of manic/hypomanic episodes over the course of one year from baseline to September-October 2017.
In total, 2231 participants were included in our study, 29.1% of whom had manic/hypomanic episodes over the course of one year from baseline. Binomial logistic regression analysis revealed that the presence of manic/hypomanic episodes was correlated with lower baseline GAF scores, rapid cycling, personality disorder, bipolar I disorder, and a mood state with manic or mixed features. Substance abuse was also a risk factor for manic episodes. There was no significant association between a baseline antidepressant prescription and manic/hypomanic episodes.
In Japan, 29.1% of outpatients with bipolar disorder had manic/hypomanic episodes over the course of one year. Our study suggested that a low GAF score, rapid cycling, personality disorder, bipolar I disorder, substance abuse, and baseline mood state could be predictors of manic/hypomanic episodes. Based on our findings, an antidepressant prescription is not a predictor of manic/hypomanic episodes.
Journal Article
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
by
Sumiyoshi, Tomiki
,
Kojima, Yoshitsugu
,
Oi, Hideki
in
Agonists
,
Antipsychotics
,
Clinical trials
2024
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. The medication persistent rate after switching from olanzapine or risperidone/paliperidone to brexpiprazole in patients with schizophrenia or schizoaffective patients was 78.5%, exceeding the predefined threshold of 65% using a longer tapering period than in the previous trial. In addition, significant improvements in functioning, well‐being, and symptoms were observed with no adverse events of concern. Brexpiprazole appeared to be a suitable antipsychotic to switch to.
Journal Article
Factors Associated with Non-Remission in Bipolar Disorder: The Multicenter Treatment Survey for Bipolar Disorder in Psychiatric Outpatient Clinics (MUSUBI)
by
Yoshimura, Reiji
,
Azekawa, Takaharu
,
Goto, Eiichiro
in
Ambulatory care facilities
,
Antidepressants
,
Antipsychotic agents
2020
The aim of this study was to identify factors associated with non-remission in bipolar disorder.
The multicenter treatment survey for bipolar disorder in psychiatric outpatient clinics (MUSUBI) study used a questionnaire administered at 176 clinics throughout Japan from September to October 2016. Clinic psychiatrists performed a retrospective medical record survey of consecutive cases with bipolar disorder. Patients were considered to be in remission if they met all of the following criteria: they were not in a mixed state, their manic or depressive symptoms were either borderline or nonexistent (corresponding to 2 or 1 points on the Clinical Global Impressions Scale, Bipolar Version), and their psychiatrists clinically considered them to be in remission. Enrolled patients were classified into remitters group and non-remitters group and demographic and clinical characteristics were contrasted between the groups. Non-remitters were compared with remitters, using a series of logistic regression analyses.
A total of 3130 patients (1420 men; mean age: 50.3 years) were included in this study; 1307 patients (41.8%) were in remission. Of the remaining 1823 patients, 1260 (40.3%) had mild to severe depression, 261 (8.3%) suffered from manic or hypomanic episodes, and 302 (9.6%) were in a mixed state. Logistic regression analyses found the following eight factors to be significantly correlated with non-remission in patients with bipolar disorder: female gender, younger age, unemployed status, rapid cycling pattern, comorbid alcohol/substance abuse, poorer social function, lithium non-use, and antidepressant use.
The MUSUBI study, the largest nationwide investigation on bipolar disorder, identified eight clinically relevant factors associated with non-remission in bipolar patients. They have important clinical implications; further prospective studies are necessary to replicate these findings and to guide better managements for those in serious needs.
Journal Article
Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications
by
Tokumitsu, Keita
,
Yoshimura, Reiji
,
Edagawa, Koji
in
Affective disorders
,
Alcohol
,
Anxiolytics
2023
Background
Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings.
Methods
This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019.
Results
A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce.
Conclusions
In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.
Journal Article
Relationship Between Employment Status and Unstable Periods in Outpatients with Bipolar Disorder: A Multicenter Treatment Survey for Bipolar Disorder in Psychiatric Outpatient Clinics (MUSUBI) Study
by
Yoshimura, Reiji
,
Fujino, Yoshihisa
,
Edagawa, Koji
in
Bipolar disorder
,
Care and treatment
,
Diagnosis
2022
To clarify the relationship between the length of unstable periods and employment status of patients with bipolar disorder.
Medical records of outpatients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics were investigated during September-October 2016, and details of their medical care and employment were surveyed using a questionnaire. The odds ratios (ORs) of length of unstable period and unemployment were analyzed with a logistic regression model.
The study included 816 patients, of whom 707 were employed full-time (continuous employment) and 70 were unemployed (loss of employment). Univariate analysis showed that ORs were statistically significant for patients who were unstable for \"almost all\" of the year (OR = 10.4 [4.48-24.28] p < 0.001), but not for \"few\" unstable periods (OR = 1.06 [0.56-1.98] p = 0.849) and for \"significant\" unstable periods (OR = 1.65 [0.73-3.74] p = 0.231) were not significantly different. Multivariate analysis showed that ORs were statistically \"significant\" for patients who were unstable for \"almost all\" (OR = 12.1 [4.37-33.3] p < 0.001), but not for \"few\" unstable periods (OR = 1.07 [0.55-2.07] p = 0.846) and for \"significant\" unstable periods (OR = 1.62 [0.66-3.98] p = 0.290) did not differ significantly.
Patients with bipolar disorder with a long unstable period were associated with a higher risk of unemployment.
Journal Article
Effect of age and sex on prescriptions for outpatients with bipolar disorder in the MUSUBI study: a cross‑sectional study
by
Yoshimura, Reiji
,
Edagawa, Koji
,
Azekawa, Takaharu
in
Age groups
,
Antidepressants
,
Antipsychotics
2022
Background
Childbearing-aged female patients and elderly patients with bipolar disorder need special attention for pharmacological treatments, but current guidelines provide little information on their pharmacological treatment. In particular, the risk/benefit balance of pharmacological treatment for childbearing-aged females with bipolar disorder is a growing concern. Therefore, we aimed to address the effect of age and sex on psychotropic drug prescription for outpatients with bipolar disorder.
Methods
The MUlticenter treatment SUrvey for BIpolar disorder in Japanese psychiatric clinics (MUSUBI) study was conducted, and data on age, sex, and details of pharmacological treatment were collected.
Results
A total of 3106 outpatients were included in this study. Among young females (age ≤ 39), 25% were prescribed valproate. There was no significant difference in the frequency and daily dose of valproate prescription for young females among all groups. Valproate prescriptions were significantly less frequent among young males and more frequent among middle-aged males. Lithium prescriptions were significantly less frequent among young females and more frequent among older males (age ≥ 65) and older females. Lamotrigine prescriptions were significantly more frequent among young males and young females and less frequent among older males and older females. Carbamazepine prescriptions were significantly less frequent among young males and more frequent among older males.
Conclusions
Biased information about the risk and safety of valproate and lithium for young females was suggested, and further study to correct this bias is needed. Older patients were prescribed lithium more commonly than lamotrigine. Further studies are needed to determine the actual pharmacotherapy for elderly individuals.
Journal Article
Relationship Between Mood Episode and Employment Status of Outpatients with Bipolar Disorder: Retrospective Cohort Study from the Multicenter Treatment Survey for Bipolar Disorder in Psychiatric Clinics (MUSUBI) Project
by
Yoshimura, Reiji
,
Fujino, Yoshihisa
,
Edagawa, Koji
in
Bipolar disorder
,
Cohort analysis
,
Comorbidity
2021
The objective of this study was to clarify the relationship between mood episode and employment in patients with bipolar disorder to help improve their employment status.
All medical records of patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics in September-October 2016 were investigated in September-October 2017. Details of the medical care received were investigated using a survey sheet, which included employment status. Odds ratios of mood episodes for employment status were analyzed using a logistic regression model.
Among patients aged 60 years or less, 2292 described their occupation. On univariate analysis, odds ratios were statistically significant for depressive episode (OR = 2.68 [1.50-4.78] p = 0.001) and manic episode (OR = 2.64 [1.07-6.47] p = 0.034), whereas no significant difference was noted for mixed episode (OR = 1.72 [0.69-4.33] p = 0.246). On multivariate analysis, odds ratios were statistically significant for depressive episode (OR = 2.16 [1.13-4.13], p = 0.020) and manic episode (OR = 3.55 [1.36-9.25], p = 0.010), whereas no significant difference was noted for mixed episode (OR = 1.83 [0.65-5.14] p = 0.254).
Employment status among these patients with bipolar disorder receiving outpatient treatment was 43.5%. Compared to remission episodes, manic and depressive episodes were associated with a higher risk of unemployment.
Journal Article
The Use of the Japanese Public Financial Support Has Positive Impact on Persistence with Outpatient Treatments for Schizophrenia: Single-center Retrospective Cohort Study in Japan
by
Ota, Kazumi
,
Ohashi, Shizuko
,
Funaoka, Yoichi
in
Ambulatory medical care
,
Cohort analysis
,
Data collection
2021
One of the challenges of treating schizophrenia is how to improve persistence with outpatient treatments. Lengthening community life by improving persistence and preventing relapse and rehospitalization can have positive influence on the patients' personal recovery and well-being. In Japan, there is \"Medical Expenses for Services and Supports for Persons with Disabilities\" (\"Jiritsu-shien-iryo-hi\" in Japanese) which is the public financial support system for psychiatric outpatient treatments. However, it is not clear how this financial support affects persistence with outpatient treatments for patients with schizophrenia. The purpose of the study is to investigate how the financial support affects persistence with outpatient treatments for schizophrenia.
Data of outpatients who visited the clinic between October 1, 2006 and September 30, 2016 was collected. The variables for the analysis were continuation and discontinuation of treatment of those who used the financial support (user) and those who did not (nonuser). The covariates were sex, age, time from onset of the disease to first visit to the clinic, number of hospitalizations in the past, use of psychiatric day care, and use of psychiatric home nursing care. Kaplan-Meier analysis was performed using propensity score matching. The observation period was five years from the first visit to the clinic.
Among 1155 patients who were diagnosed with schizophrenia, 718 were excluded, based on the exclusion criteria. The propensity score matching was performed for 437 patients, and the subjects for the final analysis were 278. Average survival period was 1.09 (SD ±1.66) years for nonuser, 3.02 (SD ±1.77) years for users, and users exhibited a significantly longer number of years of outpatient treatments (
<0.001).
The results indicated that use of the financial support can contribute to persistence with outpatient treatments.
Journal Article
An observational study of duloxetine versus SSRI monotherapy in Japanese patients with major depressive disorder: subgroup analyses of treatment effectiveness for pain, depressive symptoms, and quality of life
by
Kuga, Atsushi
,
Tanaka, Kazuhide
,
Escobar, Rodrigo
in
Analysis
,
Antidepressants
,
Care and treatment
2017
To examine how clinical and demographic patient baseline characteristics influence effectiveness of duloxetine versus selective serotonin reuptake inhibitor (SSRI) treatment, in real-world Japanese clinical settings of patients with major depressive disorder (MDD) and associated painful physical symptoms (PPS).
This was a multicenter, 12-week, prospective, observational study in patients with MDD (Quick Inventory of Depressive Symptomatology ≥16) and at least moderate PPS (Brief Pain Inventory-Short Form [BPI-SF] average pain ≥3). Patients received duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine). Assessments were made by using BPI-SF average pain, 17-item Hamilton Rating Scale for Depression (HAM-D17), EuroQol 5-dimension questionnaire, Social Adaptation Self-Evaluation Scale, Global Assessment of Functioning, and ability to work. Predefined subgroups included the number of previous episodes of depression (0 vs ≥1), baseline BPI-SF average pain score (≤6 vs >6), baseline HAM-D17 total score (≤18 vs >18), baseline HAM-D17 retardation (≤7 vs >7) and anxiety somatic subscale scores (≤6 vs >6), and age (<65 vs ≥65 years).
Treatment effectiveness was evaluated in 523 patients (duloxetine N=273, SSRIs N=250). Treatment with duloxetine was superior to SSRIs on most outcome measures in patients experiencing their first depressive episode, those with higher baseline PPS levels, and in patients with more severe baseline depression. This was also the case for older patients. In patients with less severe depression, SSRI treatment tended to show more improvements in depression and quality of life measures versus duloxetine treatment.
These preplanned subgroup analyses of data from a prospective observational study suggest that, for Japanese MDD patients with PPS, duloxetine is more effective than SSRIs in patients with a first episode of MDD, with more severe depression, or more severe PPS.
Journal Article
An observational study of duloxetine versus SSRI monotherapy for the treatment of painful physical symptoms in Japanese patients with major depressive disorder: primary analysis
by
Kuga, Atsushi
,
Tanaka, Kazuhide
,
Escobar, Rodrigo
in
Analysis
,
Antidepressants
,
Clinical outcomes
2017
The objective of this study was to assess the effectiveness of duloxetine monotherapy, in comparison with selective serotonin reuptake inhibitor (SSRI) monotherapy, in the treatment of painful physical symptoms (PPS) in Japanese patients with major depressive disorder (MDD) in real-world clinical settings.
This was a multicenter, 12-week prospective, observational study. This study enrolled MDD patients with at least moderate PPS, defined as a Brief Pain Inventory-Short Form (BPI-SF) average pain score (item 5) ≥3. Patients were treated with duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine) for 12 weeks, and PPS were assessed by BPI-SF average pain score. The primary outcome was early improvement in the BPI-SF average pain score at 4 weeks post-baseline.
A total of 523 patients were evaluated for treatment effectiveness (duloxetine N=273, SSRIs N=250). The difference in BPI-SF average pain score between the two groups was not statistically significant at 4 weeks post-baseline, the primary endpoint (least-squares mean change from baseline [95% confidence interval]: duloxetine, -2.8 [-3.1, -2.6]; SSRIs, -2.5 [-2.8, -2.3];
=0.166). There was a numerical advantage for duloxetine in improvement from 4 to 12 weeks post-baseline, and the difference was statistically significant at 8 weeks post-baseline (least-squares mean change from baseline [95% confidence interval]: duloxetine, -3.6 [-3.9, -3.3]; SSRIs, -3.1 [-3.4, -2.8];
=0.023). The 30% and 50% responder rates were significantly higher in patients treated with duloxetine at 4 and 8 weeks post-baseline. There were no serious adverse events experienced by duloxetine-treated patients. The rate of discontinuations due to adverse events was similar for duloxetine and the SSRIs (1.0% and 0.8% of patients, respectively).
In this observational study, BPI-SF improvement was not significantly different at 4 weeks, the primary endpoint; however, patients treated with duloxetine tended to show better improvement in PPS compared to those treated with SSRIs.
Journal Article