Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications.

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.

Effect of age and sex on prescriptions for outpatients with bipolar disorder in the MUSUBI study: a cross­sectional study.

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.

Estimated model of psychotropic polypharmacy for bipolar disorder: Analysis using patients' and practitioners' parameters in the MUSUBI study.

OBJECTIVE: This study aims to clarify the relevant factors influencing practitioners' methods of prescribing medications for bipolar disorder, in a nation-wide survey in Japan. METHODS: The clinical records of 3130 outpatients with bipolar disorder were consecutively reviewed from 176 psychiatric outpatient clinics. Fifteen parameters, that is, five patients' including five general characteristics (sex, age, education, occupation, and social adjustment), five patients' aspects of mental functioning (onset age, comorbid mental illness, rapid-cycling, psychopathologic severity, and followed-up years), and five practitioners' characteristics (sex, age, specialist experience, clinic standing years, and location), were evaluated. The number of psychotropic drugs (mood stabilizers, antidepressants, antipsychotic drugs, anxiolytics, and hypnotics) was used as an index of pharmacotherapy. Converted data from each practitioner-unit were analyzed. RESULTS: Seven factors (patient's social adjustment, patient's psychopathology, patient's comorbid mental disorders, patient's followed-up years, doctor's age, clinic running years, and patient's education years) were correlated to the number of psychotropic drugs. Multiple regression analysis showed that the severity of illness (poor social adjustment, and comorbid mental illness) and an intractable disease course (long followed-up years), were significantly associated with the number of psychotropic drugs. CONCLUSION: Our findings indicated that patient-related conditions affected psychotropic polypharmacy more strongly than did practitioner-related conditions.

Real-world clinical features of and antidepressant prescribing patterns for outpatients with bipolar disorder.

BACKGROUND: Several evidence-based practice guidelines have been developed to better treat bipolar disorder. However, the articles cited in these guidelines were not sufficiently based on real-world clinical practice. METHODS: The MUlticenter treatment SUrvey on BIpolar disorder in Japanese psychiatric clinics (MUSUBI) is a study conducted to accumulate evidence on the real-world practical treatment of bipolar disorder. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder by performing a retrospective medical record survey. The questionnaire included patient characteristics (age, gender, height, weight, academic background, and occupational status), comorbidities, mental status, treatment period, Global Assessment of Functioning (GAF) score, and details of pharmacological treatment. RESULTS: Data on 2705 patients were included in this study. The proportion of patients receiving antidepressant prescriptions was 40.9%. The most commonly used antidepressant was duloxetine, and the most frequently used antidepressant class was selective serotonin reuptake inhibitors (SSRIs). Binomial logistic regression analysis and bivariate analysis revealed that the usage of antidepressants was correlated with low prescription rates for mood stabilizers, high prescription rates for anxiolytics and hypnotics, and low GAF scores. In addition, patients in a depressive state had a significantly higher rate of antidepressant prescriptions than patients with other mental states. CONCLUSIONS: Approximately 40% of patients in Japan with a diagnosis of bipolar disorder have received antidepressants. Antidepressants were most often prescribed in combination with mood stabilizers, antipsychotics or both. Patients who were prescribed antidepressants received fewer mood stabilizers, more anxiolytics, and more hypnotics than those who did not receive antidepressant prescriptions.

Costs of psychotropics for outpatients with bipolar disorder in Japan; the MUSUBI 2016 survey.

BACKGROUND: Although the costs of bipolar disorder (BD) treatments are associated with local and universal factors, data from non-Western countries remain limited. The associations between clinical features and costs of outpatient pharmacotherapy have not been well characterize. To estimate the costs of outpatient BD treatments and their associations with clinical features in a Japanese population, we investigated with special reference to the costs of medicines constituted the bulk of the total healthcare expense and were steadily increasing. METHODS: The Multicenter Treatment Survey for Bipolar Disorder (MUSUBI) retrospectively evaluated 3130 patients with BD who visited 176 Japanese psychiatric outpatient clinics in 2016. Clinical features and drug prescriptions were recorded, and the total daily costs of psychotropic drug treatment were calculated. The annual medical costs related to outpatient BD treatments in Japan were estimated based on the corresponding demographics. The associations between daily medical costs and patients' clinical features were analyzed using multiple regression analysis. RESULTS: The daily costs of psychotropic drugs ranged from zero to JPY3245 (mean, JPY349 equivalent to USD32.5) and were exponentially distributed. The annual costs for outpatients BD treatments were approximately 51.9 billion Japanese yens (519 million US dollars). Subsequent multiple regression analysis revealed that social adjustment, depressive symptoms, age, rapid cycling, psychotic symptoms, and comorbid mental disorders correlated strongly with the daily cost of psychotropic drugs. CONCLUSION: The estimated annual costs for outpatient BD treatment in Japan were equivalent to those in OECD countries (except for the US) and higher than those in some Asian countries. The cost of psychotropic treatments was associated with individual characteristics and psychopathological conditions.Key MessagesPsychotropic treatment for an outpatient with bipolar disorder has a daily cost approximately JPY350.The annual outpatient treatment cost for bipolar disorder in Japan was estimated to 51.9 billion Japanese yen in 2016.Individual characteristics and psychopathological conditions affected the cost of drug treatment.

Clinical characteristics and prescriptions associated with a 2-year course of rapid cycling and euthymia in bipolar disorder: a multicenter treatment survey for bipolar disorder in psychiatric clinics.

Objective: In patients with bipolar disorder (BD), rapid cycling (RC) presents a risk for a more severe illness, while euthymia (EUT) has a better prognosis. This study focused on the progression of RC and EUT, which are contrasting phenomenology, and aimed to clarify the influence of patient backgrounds and prescription patterns on these different progressions, using a large sample from the first and second iterations of a multicenter treatment survey for BD in psychiatric clinics (MUSUBI). Methods: In the cross-sectional study (MUSUBI), a questionnaire based on a retrospective medical record survey of consecutive BD cases (N = 2,650) was distributed. The first survey was conducted in 2016, and the second one in 2017. The questionnaire collected information on patient backgrounds, current episodes, and clinical and prescribing characteristics. Results: In the first survey, 10.6% of the participants had RC and 3.6% had RC for two consecutive years, which correlated with BP I (Bipolar disorder type I), suicidal ideation, duration of illness, and the use of lithium carbonate and antipsychotic medications. Possible risk factors for switching to RC were comorbid developmental disorders and the prescription of anxiolytics and sleep medication. Moreover, 16.4% of the participants presented EUT in the first survey, and 11.0% presented EUT for two consecutive years. Possible factors for achieving EUT included older age; employment; fewer psychotic symptoms and comorbid personality disorders; fewer antidepressants, antipsychotics, and anxiolytics, and more lithium prescriptions. Conclusion: RC and EUT generally exhibit conflicting characteristics, and the conflicting social backgrounds and factors contributing to their outcomes were distinctive. Understanding these clinical characteristics may be helpful in clinical practice for management of patients with BD.

Predictors of psychiatric hospitalization among outpatients with bipolar disorder in the real-world clinical setting.

Background: Bipolar disorder is a psychiatric disorder that causes recurrent manic and depressive episodes, leading to decreased levels of social functioning and suicide. Patients who require hospitalization due to exacerbation of bipolar disorder have been reported to subsequently have poor psychosocial functioning, and so there is a need to prevent hospitalization. On the other hand, there is a lack of evidence regarding predictors of hospitalization in real-world clinical practice. Methods: The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was an observational study conducted to provide evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked, as part of a retrospective medical record survey, to fill out a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. Our study extracted baseline patient characteristics from records dated between September and October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. The incidence and predictors of hospitalization among patients with bipolar disorder over a 1-year period extending from that baseline to September-October 2017 were examined. Results: In total, 2,389 participants were included in our study, 3.06% of whom experienced psychiatric hospitalization over the course of 1 year from baseline. Binomial logistic regression analysis revealed that the presence of psychiatric hospitalization was correlated with bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and manic state. Conclusions: Our study revealed that 3.06% of outpatients with bipolar disorder were subjected to psychiatric hospitalization during a 1-year period that extended to September-October 2017. Our study suggested that bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and baseline mood state could be predictors of psychiatric hospitalization. These results may be useful for clinicians seeking to prevent psychiatric hospitalization for bipolar disorder.

Differences in prescription patterns between real-world outpatients with bipolar I and II disorders in the MUSUBI survey.

OBJECTIVE: There is limited information available on the prescription of psychotropic agents to patients with bipolar I (BD-I) and bipolar II disorder (BD-II). The purpose of this study was to investigate the characteristics of drug therapy in BD-I and BD-II outpatients, particularly with regard to antidepressants. METHODS: In 2017, the MUlticenter treatment SUrvey for BIpolar disorder in Japanese psychiatric clinics (MUSUBI) study collected data on current mental status, medications, and other factors from 2774 outpatients with BD-I or BD-II. RESULTS: There were significant differences in the rates of prescriptions for mood stabilizers, antipsychotics and antidepressants. Mood stabilizers and antipsychotics were prescribed at higher rates to patients with BD-I (mood stabilizers; BD-I 86.0%, BD-II 80.8%, p < 0.001; antipsychotics; BD-I 61.5%, BD-II 47.8%, p < 0.001), and antidepressants were prescribed at higher rates to patients with BD-II (BD-I 32.1%, BD-II 46.4%, p < 0.001). The most commonly prescribed antidepressants were escitalopram for patients with BD-I and duloxetine for patients with BD-II. Selective serotonin reuptake inhibitors (SSRIs) were the most common class of antidepressants prescribed to patients with BD. With regard to combination therapy, combinations containing antidepressants were often prescribed to patients with BD-II. CONCLUSION: There was a difference in the prescription of psychotropic agents between patients with BD-I and BD-II. The outpatient prescriptions for BD in Japan were mood stabilizers and antipsychotics, which generally followed the guidelines. There is insufficient evidence regarding the effects of the prescribed antidepressants and the risk of manic episodes, and further evidence needs to be collected.

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.

Purpose: To clarify the relationship between the length of unstable periods and employment status of patients with bipolar disorder. Patients and Methods: 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. Results: 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. Conclusion: Patients with bipolar disorder with a long unstable period were associated with a higher risk of unemployment.

Determinants of three-year clinical outcomes in real-world outpatients with bipolar disorder: The multicenter treatment survey for bipolar disorder in psychiatric outpatient clinics (MUSUBI).

BACKGROUND: There is limited evidence regarding predictors of long-term clinical outcomes in patients with bipolar disorder (BD). The objective of this study was to describe 3-year clinical outcomes and identify their predictors from participants in the multicenter treatment survey for BD in psychiatric outpatient clinics (MUSUBI). METHODS: The MUSUBI was a naturalistic study investigating patients with BD in real-world clinical practice. Our study extracted data regarding 1647 outpatients with BD from 2016, 2017, and 2019 as baseline, 1-year, and 3-year assessments. As clinical outcomes, we assessed the presence of time ill (depressive and manic) during the 1 year prior to the 3-year assessment and durable remission (53 weeks or more) prior to the 3-year assessment. RESULTS: Participants with durable remission prior to the 3-year assessment had significant associations with diagnosis of a personality disorder and duration of continuous remission at baseline. Regarding the presence of depressive symptoms during the 1 year prior to the 3-year assessment, work status, Global Assessment of Functioning (GAF) scores, suicidal ideation, and duration of continuous remission at baseline had significant associations with this outcome. CONCLUSIONS: At the 3-year assessment, 19.3% of participants (318/1647) achieved durable remission, while 47.5% of them (782/1647) were not remitted. Our findings can help clinicians predict the illness course of BD by understanding demographic and clinical characteristics.

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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Real-world clinical predictors of manic/hypomanic episodes among outpatients with bipolar disorder.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Factors Associated with Doses of Mood Stabilizers in Real-world Outpatients with Bipolar Disorder.

OBJECTIVE: : Several evidence-based practice guidelines have been developed to better treat bipolar disorder. However, the articles cited in these guidelines were based on clinical or basic studies with specific conditional settings and were not sufficiently based on real-world clinical practice. In particular, there was little information on the doses of mood stabilizers. METHODS: The MUlticenter treatment SUrvey on BIpolar disorder in Japanese psychiatric clinics (MUSUBI) is a study conducted to accumulate evidence on the real-world practical treatment of bipolar disorder. The questionnaire included patient characteristics such as comorbidities, mental status, treatment period, Global Assessment of Functioning (GAF) score, and details of pharmacological treatment. RESULTS: Most patients received mood stabilizers such as lithium (n = 1,317), valproic acid (n = 808), carbamazepine (n = 136), and lamotrigine (n = 665). The dose of lithium was correlated with age, body weight, number of episodes, depression and GAF. The dose of valproic acid was correlated with body weight, number of episodes, presence of a rapid cycle and GAF. The dose of carbamazepine was correlated with age, mania, and the presence of a rapid cycle. The dose of lamotrigine was correlated with the number of episodes, depression, mania, psychotic features, and the presence of a rapid cycle. Doses of coadministered mood stabilizers were significantly correlated, except for the combination of valproic acid and lamotrigine. CONCLUSION: The dose of mood stabilizers was selectively administered based on several factors, such as age, body composition, current mood status and functioning. Further prospective studies are required to confirm these findings.

Factors Associated with Non-Remission in Bipolar Disorder: The Multicenter Treatment Survey for Bipolar Disorder in Psychiatric Outpatient Clinics (MUSUBI).

PURPOSE: The aim of this study was to identify factors associated with non-remission in bipolar disorder. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical features related to rapid cycling and one-year euthymia in bipolar disorder patients: A multicenter treatment survey for bipolar disorder in psychiatric clinics (MUSUBI).

OBJECTIVE: Rapid cycling (RC) presents a risk of greater severity in bipolar disorder (BD), whereas patients with one-year euthymia (OYE) have better prognosis. The purpose of this study was to identify the clinical background and prescription characteristics of patients in the two opposing states of current RC and OYE from a large sample (N = 2609) in a multicenter treatment survey on BD in psychiatric clinics (MUSUBI). METHODS: MUSIBI was a cross-sectional study wherein questionnaires, based on a retrospective medical record survey of consecutive cases of BD, were distributed to 176 outpatient clinics. The questionnaire collected information on patient background, current episode, and clinical and prescription characteristics. OYE was defined as the presence of a euthymic state for at least 12 months. RESULTS: In this study, current RC (9.7% frequency) was significantly higher in females, had a younger age of onset, functional impairments, and a higher rate of neurodevelopmental disorder and physical comorbidity compared to non-RC patients. OYE (19.4% frequency) was associated with a lower proportion of females, older age, higher occupational status, and lower rate of suicide ideation, psychotic symptoms, personality disorder, and alcohol or substance abuse. Mood stabilizers were prescribed in ≥80% of cases, while antipsychotics were prescribed in half of the cases (more in RC and less in OYE). Antidepressant prescription rates were lower in OYE than in RC. CONCLUSIONS: RC and OYE generally show opposing characteristics, but the details of the opposite parameters are distinctive. Clinicians can help predict the progression of BD by understanding the clinical background and characteristics of these opposing clinical features.