Middle meatus microbiome in patients with eosinophilic chronic rhinosinusitis in a Japanese population.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease and is subdivided into eosinophilic and noneosinophilic forms. There are few reports investigating the nasal microbiome and its pathological functions in patients with CRS. OBJECTIVE: We sought to analyze factors contributing to variations of the nasal microbiome in CRS, and on the basis of these factors, to elucidate whether the bacterial metabolites were related to the pathogenesis. METHODS: Nasal swabs were collected, and the V3 to V4 variable region of the 16S ribosomal RNA gene was amplified and sequenced. Factors contributing to variations of the nasal microbiome in patients with CRS were compared. The most influential factor was whether CRS was eosinophilic, and we compared α- and ß-diversity, bacterial species, and predictive bacterial functions between the 2 patient groups. In addition, the metabolites of the key bacteria were extracted, and we evaluated the predicted bacterial functions in airway epithelial cells. RESULTS: In total, 110 patients with CRS and 33 control subjects were enrolled. On the basis of the factors of variation, it was found that patients with eosinophilic CRS (n = 65) had different microbiomes with weighted UniFrac ß-diversity and lower α-diversity compared with those with noneosinophilic CRS (n = 45). A higher abundance of Fusobacterium nucleatum and an increased LPS pathway were observed in patients with noneosinophilic CRS compared with those with eosinophilic CRS. In airway epithelial cells, LPS derived from F nucleatum suppressed the expression levels of ALOX15 induced by TH2 cytokines. CONCLUSIONS: The differences in the nasal microbiome may play a key role in the pathophysiology of CRS.

Psychoses after an antiepileptic drug administration: Frequency, timing, and duration.

OBJECTIVES: To clarify the pathophysiology of psychoses after the new administration of antiepileptic drugs (AED), we analyzed the annual incidence, timing of development, and duration of episodes. METHODS: Psychotic outcomes in the first 6-month period after an AED or non-AED administration in patients with focal epilepsy were exhaustively reviewed in eight Japanese neuropsychiatry institutions. In cases with psychotic episodes, the subtype of psychosis, timing of development, previous history of psychosis, and duration of the episode were evaluated. RESULTS: Between 1981 and 2015, 5018 new drugs (4402 AED and 616 non-AED) were administered to 2067 patients with focal epilepsy. In the first 6-month period, 105 psychotic episodes occurred (81 interictal psychosis [IIP] and 24 postictal psychosis). Furthermore, 55 cases were first episodes and 50 were recurrent episodes. The frequency of psychoses is significantly higher after AED administration (n = 102) compared with non-AED administration (n = 3). Psychosis occurred most frequently in the initial 1-month period after new-AED administration and tended to decrease with increasing time. The estimated annual incidence of all psychoses after a new AED administration was 3.5% (2.0% for first-episode psychosis and 1.8% for first-episode IIP). Duration of psychoses (mean, 38.5 weeks) was equivalent to overall IIP. Duration of IIP did not shorten with discontinuation of newly administered AED. SIGNIFICANCE: Patients with epilepsy exhibit psychosis more frequently after new AED administration than after non-AED administration. This study shows the pathophysiology of psychoses after AED administration with annual incidence, the timing of development, and the duration of PAP, which have rarely been reported.

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.

Epilepsy in patients with schizophrenia: Pathophysiology and basic treatments.

Schizophrenia is a chronic psychiatric disorder that may lead to epilepsy. However, there are limited findings on the issues. This narrative review aimed to provide a practical perspective on epilepsy in patients with schizophrenia using the current treatment systems for epilepsy. While there has been a debate on the relationship between epilepsy and schizophrenia, i.e., antagonism, affinity, and coincidence, recent large cohort studies have revealed a high frequency of epilepsy in patients with schizophrenia (4-5 times higher than that of general population). The high incidence observed is likely to be due to the bidirectionality between epilepsy and schizophrenia and additional schizophrenia-related conditions, e.g., antipsychotic drugs (APD), substance abuse, and head injury. As for symptomatology of epilepsy, only one small-size study showed that seizures of patients with schizophrenia are equivalent to those of patients without schizophrenia. Patients with schizophrenia exhibit the first seizure in their twenties or later, which are mostly focal seizures. Most of seizures in patients with schizophrenia can be controlled with conventional antiepileptic drugs. Few patients with schizophrenia develop treatment-resistant epilepsy. However, since drug interactions can be more complicated due to multiple conditions, such as pre-existing polypharmacy, heavy smoking, irregular eating, and comorbid metabolic disorders, cautious monitoring for clinical symptoms is required. To improve seizure control and adherence, non-pharmacological approaches are also recommended. Thus far, for seizure treatments in patients with schizophrenia, we have to use many empirical findings or substitute certain findings from population without schizophrenia because evidence is insufficient. The accumulation of clinical findings may contribute to the development of efficient treatment systems.

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.

Quantitative psychopathology of interictal psychosis in epilepsy; interaction between epilepsy-related and psychosis-general effects.

OBJECTIVE: There is a historical debate whether psychopathology of epilepsy psychosis is unique to epilepsy or common to other psychoses. However, a large comprehensive studies on this issue are scarce. To clarify the characteristics of interictal psychosis (IIP), we evaluated psychopathology quantitatively. METHODS: This study included 150 patients with IIP (epilepsy+/psychosis+), 187 patients with schizophrenia (SC: epilepsy-/psychosis+), 182 patients with epilepsy (EP: epilepsy+/psychosis-), and 172 non-clinical individuals (NC: epilepsy-/psychosis-). The IIP group comprised 127 chronic and 23 brief psychoses. Age, sex, and years of education, onset and duration of psychosis, and onset and duration of epilepsy were matched among the groups. The psychopathology was evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS), which comprises three symptom factors namely negative symptoms (NS), positive symptoms (PS), and anxiety-depressive symptoms (ADS). RESULTS: For overall 16-BPRS and NS factor scores, there were significant interactions between epilepsy-related (epilepsy+/-) and psychosis-general (psychosis+/-) effects. The EP exhibited higher scores than did the NC, whereas the IIP exhibited lower scores than did the SC. For PS and ADS factor scores, the IIP and SC exhibited a significant psychosis-general effect. Chronic IIP was associated with more serious psychopathologies than was brief IIP. However, limited with chronic IIP, there was a significant interaction between epilepsy-related and psychosis-general effects on the overall 16-BPRS and NS factor scores. CONCLUSION: These findings demonstrate the first large quantitative evidence on the unique psychopathology of IIP which has been only narratively described. The psychopathology is associated with the interaction between epilepsy-related and psychosis-general effects.

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.

Increased frequency of psychosis after second-generation antiepileptic drug administration in adults with focal epilepsy.

OBJECTIVE: Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP. METHODS: The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures. RESULTS: Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP. CONCLUSION: Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP.

Seizure activity and individual vulnerability on first-episode interictal psychosis in epilepsy.

OBJECTIVE: Despite a theoretical consensus that interictal psychosis (IIP) is related to various epilepsy-related factors, the impact of seizure activity on development of IIP remains inconclusive. This is the first controlled study using quantitative seizure-activity measures at the onset of IIP. METHODS: One hundred and eighty-one patients with epilepsy who exhibited first-episode IIP (IIP group) and 427 patients with epilepsy without psychotic episodes (control group) were enrolled. The control group was matched for age, epilepsy type, and duration of epilepsy. The two seizure-activity indices (seizure frequency at the time of onset of first-episode IIP and the number of seizures before the onset of IIP) were evaluated and compared between the IIP and control groups. Logistic regression analysis was used for extracting risk variables to develop first-episode IIP. RESULTS: The sum of previous seizures was greater in the IIP than in control groups. This was particularly the case in the patients with partial epilepsies (PE). Higher seizure frequency in the patients with PE was associated with the development of first-episode IIP while no association was found in the whole cohort or in the patients with generalized epilepsies (GE). Subsequent multivariate analysis revealed the sum of previous seizures and family history of psychosis as risk variables to first-episode IIP. CONCLUSIONS: The accumulation of seizure-related damages and family history of psychosis is associated with the onset of IIP episodes, particularly in the patients with PE. Seizure activity and individual vulnerability to psychosis are likely to be interacted for as the development of IIP in patients with epilepsy.

Pharmacotherapy in patients with epilepsy and psychosis.

The recognition and treatment of psychosis in persons with epilepsy (PWE) is recommended with the apparent dilemma between treating psychosis and opening the possibility of exacerbating seizures. The pooled prevalence estimate of psychosis in PWE is 5.6%. It has been proposed that a 'two hit' model, requiring both aberrant limbic activity and impaired frontal control, may account for the wide range of clinical phenotypes. The role of antiepileptic drugs in psychosis in PWE remains unclear. Alternating psychosis, the clinical phenomenon of a reciprocal relationship between psychosis and seizures, is unlikely to be an exclusively antiepileptic drug-specific phenomenon but rather, linked to the neurobiological mechanisms underlying seizure control. Reevaluation of antiepileptic treatment, including the agent/s being used and degree of epileptic seizure control is recommended. The authors found very few controlled studies to inform evidence-based treatment of psychosis in PWE. However, antipsychotics and benzodiazepines are recommended as the symptomatic clinical treatments of choice for postictal and brief interictal psychoses. The general principle of early symptomatic treatment of psychotic symptoms applies in epilepsy-related psychoses, as for primary psychotic disorders. In the authors' experience, low doses of antipsychotic medications do not significantly increase clinical risk of seizures in PWE being concurrently treated with an efficacious antiepileptic regimen.

Low parathyroid hormone levels after parathyroidectomy reduce cardiovascular mortality in chronic hemodialysis patients.

BACKGROUND: The aim of the study is to elucidate whether parathyroid hormone (PTH) levels after parathyroidectomy affect the prognosis of patients with secondary hyperparathyroidism. SUBJECTS AND METHODS: Two hundred and ninety-five patients, who underwent PTx without autotransplantation from July 1998 to December 2011, were divided into the low (n = 148) and high (n = 147) PTH groups, using the median value of each mean value of intact PTH after surgery (16.6 pg/mL). After observation for 5.00 years, we evaluated demographic factors, influences of postoperative mineral metabolism, magnitude of uremia, and vitamin D receptor activators on their prognosis, with the multivariate Cox proportional hazard model. RESULTS: While overall survival rates in the high and low PTH groups were 54.9 and 74.2 %, respectively (P = 0.1500), cardiovascular survival rates were 71.6 and 94.4 %, respectively (P = 0.0256). The hazard ratio for cardiovascular mortality in the high PTH group (≥16.6 pg/mL) was 3.132 (P = 0.0470), and those in groups with the median age more than 59 years and with cardiovascular disease were 2.654 (P = 0.0589) and 3.377 (P = 0.0317), respectively. The intact PTH level 6 days after surgery and the mean postoperative intact PTH value showed a strong correlation (Spearman ρ = 0.9007, P < 0.0001, y = 0.4725x + 30.395, R 2 = 0.51798). CONCLUSION: The present study suggests that maintaining low PTH levels after parathyroidectomy reduces cardiovascular mortality and improves the prognosis. Total parathyroidectomy (more than 4 glands) without autotransplantation seems to be one of the treatment options for managing severe secondary hyperparathyroidism.

Dissociative experiences in epilepsy: effects of epilepsy-related factors on pathological dissociation.

Psychogenic nonepileptic seizures (PNESs) in patients with epilepsy can be categorized as dissociative disorders. The prevalence of PNESs in patients with epilepsy appears to be much higher than that of dissociative experiences in nonclinical subjects. In order to clarify as to whether epilepsy-related factors were associated with pathological dissociation, we conducted a controlled study with 225 patients with epilepsy and 334 nonclinically matched individuals. All participants completed the Japanese version of the Dissociative Experiences Scale (DES). There was no significant difference in the DES score (DES-S) between the group with epilepsy and the control group. The group with epilepsy showed a significantly higher DES taxon (DES-T; a subset of DES-S and an index of pathological dissociation) than the control group. Thirty-one out of the 225 patients with epilepsy (13.8%) had PNESs. Because of its strong association with the DES-S and DES-T, PNESs can be regarded as a symptom of dissociation. With multiple regression analysis, the patients with a shorter duration of epilepsy, higher seizure frequency, or shorter period in education tend to suffer from pathological dissociation. These findings demonstrate that patients with epilepsy are more prone to experiencing pathological dissociation when having certain clinical factors.

Suppression of peritoneal thickening by histamine in a mouse model of peritoneal scraping.

BACKGROUND: Inflammatory reactions play an important role in peritoneal sclerosis in patients on peritoneal dialysis. Since histamine affects inflammatory reactions and immune responses, we investigated effects of intraperitoneal administration of histamine on peritonitis induced by mechanical scraping in mice. METHODS: After anesthesia, the right peritoneum was scraped 90 times over 1 min, and bilateral peritonea were observed by light microscopy after 7 days. RESULTS: Thickness of the peritoneal membrane on the right side was 174 ± 77 µm (mean ± SD, n = 8), while that on the left side was 24 ± 19 µm. Intraperitoneal administration of histamine (0.3 or 1.0 mmol/L, 0.5 mL each) twice daily for 7 days after scraping decreased thickness of the right peritoneum to 42 and 43 % of that in saline-injected animals, respectively (P < 0.01), although histamine (0.1 mmol/L) did not affect it. Promethazine (5 nmol, twice daily for 7 days), a histamine H1 receptor antagonist, abolished the amelioration caused by histamine (1.0 mmol/L). Neither ranitidine (15 nmol), a histamine H2 receptor antagonist, nor thioperamide (7.5 nmol), a histamine H3/H4 receptor antagonist, affected the outcome in histamine-treated mice. CONCLUSION: These findings indicate that histamine H1 action partly prevents the development of peritoneal fibrosis caused by mechanical scraping.

Basic treatment principles for psychotic disorders in patients with epilepsy.

In patients with epilepsy, coexisting psychoses, either interictal (IIP) or postictal (PIP), are associated with serious disturbance in psychosocial function and well-being, and often require the care of a specialist. Unfortunately, evidence-based treatment systems for psychosis in patients with epilepsy have not yet been established. This article aims to propose concise and practical treatment procedures for IIP and PIP based on currently available data and international consensus statements, and primarily targeting nonpsychiatrist epileptologists who are often the first to be involved in the management of these complex patients. Accurate and early diagnosis of IIP and PIP and their staging in terms of acuity and severity form the essential first step in management. It is important to suspect the presence of psychosis whenever patients manifest unusual behavior. Knowledge of psychopathology and both individual and epilepsy-related vulnerabilities relevant to IIP and PIP facilitate early diagnosis. Treatment for IIP involves (1) obtaining consent to psychiatric treatment from the patient, whenever possible, (2) optimization of antiepileptic drugs, and (3) initiation of antipsychotic pharmacotherapy in line with symptom severity and severity of behavioral and functional disturbance. Basic psychosocial interventions will help reinforce adherence to treatment and should be made available. Due consideration must be given to patients' ability to provide informed consent to treatment in the short term, with the issue being revisited regularly over time. Given the often prolonged and recurrent nature of IIP, treatment frequently needs to be long-term. Treatment of PIP consists of two aspects, that is, acute protective measures and preventive procedures in repetitive episodes. Protective measures prioritize the management of risk in the early stages, and may involve sedation with or without the use of antipsychotic drugs, and the judicious application of local mental health legislation if appropriate. As for preventative procedures, optimizing seizure control by adjusting antiepileptic drugs or by surgical treatment is necessary.

Effects of antipsychotic drugs on the duration of interictal psychotic episodes in patients with epilepsy.

Treatment protocols for interictal psychosis (IIP) of patients with epilepsy have not yet been established. We aimed to clarify the effects of antipsychotic drugs (APDs) on duration of IIP episodes. We studied 393 IIP episodes in 200 patients with epilepsy in accordance with our empirical treatment protocol. The duration of all the episodes and APD treatments were reviewed. Antipsychotic drugs were used in 338 episodes and not used in 55 episodes (non-APD group). The APDs used in the treatment of IIP episodes were divided into the following three groups: first-generation APDs (FAPD, n=252), second-generation APDs (SAPD, n=44), and the combination of first- and second-generation APDs (CAPD, n=42). The non-APD group showed a significantly shorter episode duration than did the APD group (F=6.05, p=0.014). Among the 3 APD groups (FAPD, SAPD, and CAPD), there was a significant difference in duration of IIP episode (F=8.65, p=0.000). Whereas the duration of episodes was significantly longer in the CAPD group than in the other two groups, it was not significantly different between the FAPD and SAPD groups. Our findings further to clarify the nature of IIP and add further perspectives on treatment protocols for IIP.

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.