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Background: Bipolar disorder is a psychiatric disorder characterized by mood swings between manic and depressed states that causes psychosocial problems. Cognitive function deteriorates with each recurrence, making it important to maintain remission through continued treatment. Bipolar disorder often co-occurs with alcohol dependence, which is known to lead to decreased treatment adherence and increased suicide risk. However, the real-world clinical determinants of alcohol dependence in outpatients with bipolar disorder in Japan remain unclear., Methods: We conducted an observational study targeting 2392 patients with bipolar disorder using data from the MUSUBI study, a joint project of the Japanese Association of Neuro-Psychiatric Clinics and the Japanese Society of Clinical Neuropsychopharmacology. After determining the prevalence of alcohol dependence and the sociodemographic characteristics of patients with bipolar disorder, multivariate analysis was performed to identify risk factors for alcohol comorbidity., Results: The prevalence of alcohol dependence among outpatients with bipolar disorder in this study was 5.7%. The prevalence was 7.6% for males and 3.1% for females. The results of the binomial logistic regression analysis revealed that bipolar I disorder, manic state, comorbidities with other psychiatric disorders, male sex, and suicidal ideation were significantly associated with alcohol dependence. Stratified analysis by gender showed that alcohol dependence was more strongly associated with the presence of suicidal ideation in women than in men., Limitation: First, because this was an observational study with a cross-sectional design, causal relationships between factors cannot be determined. In addition, this study included outpatients in Japan but lacked information on inpatients. Therefore, it was considered necessary to conduct the study on a larger population in order to generate more robust evidence., Conclusions: We found that outpatients with bipolar disorder, especially men, had higher rates of alcohol dependence overall than the general population in Japan. In addition, the relationship between alcohol dependence and suicidal ideation was stronger in women than in men with bipolar disorder. There was a strong association between manic states and alcohol dependence in outpatients with bipolar disorder. These results are useful to clinicians because they reinforce real-world clinical evidence for the treatment of bipolar disorder and co-occurring alcohol dependence., Competing Interests: YK has received consultant fees from Pfizer and Meiji-Seika Pharma and speaker’s honoraria from Meiji-Seika Pharma, MSD, Eli Lilly, Janssen Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Yoshitomi Yakuhin, Otsuka Pharmaceutical, Takeda Pharmaceutical, Lundbeck Japan, and Eisai. TA has received speaker’s honoraria from Eli Lilly, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma and Eisai. HU has received manuscript fees or speaker’s honoraria from Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Yoshitomi Yakuhin. KE has received speaker’s honoraria from Eli Lilly, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Kyowa, Yoshitomi Yakuhin, and Takeda Pharmaceutical. EK has received speaker’s honoraria from Daiichi Sankyo, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, UCB, and Viatris. SH has received manuscript fees or speaker’s honoraria from Eli Lilly, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Yoshitomi Yakuhin. EG has received manuscript fees or speaker’s honoraria from Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Takeda Pharmaceutical, Eisai, Ono Pharmaceutical, Kyowa Pharmaceutical Industry and Sumitomo Dainippon Pharma. HU has received manuscript fees or speaker’s honoraria from Eli Lilly, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Dainippon Sumitomo Pharma, Takeda Pharmaceutical, Lundbeck Japan and Yoshitomi Yakuhin. MK has received grant funding from the Japanese Ministry of Health, Labor and Welfare, the Japan Society for the Pro- motion of Science, SENSHIN Medical Research Foundation, the Japan Research Foundation for Clinical Pharmacology and the Japanese Society of Clinical Neuropsychopharmacology and speaker’s honoraria from Sumitomo Dainippon Pharma, Otsuka, Meiji-Seika Pharma, Eli Lilly, MSD K.K., Pfizer, Janssen Pharmaceutical, Shionogi, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Lundbeck and Ono Pharmaceutical and participated in an advisory/review board for Otsuka, Sumitomo Dainippon Pharma, Shionogi and Boehringer Ingelheim. RY has received speaker’s honoraria from Eli Lilly, Dainippon Sumitomo, Otsuka, and Esai. AN has received speaker’s honoraria from Pfizer, Eli Lilly, Otsuka, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida, Dainippon Sumitomo and NTT Docomo, and participated in an advisory board for Takeda, Meiji Seika, Tsumura and Yoshitomi Yakuhin. TK has received consultant fees from Takeda Pharmaceutical and the Center for Cognitive Behavioral Therapy and Training. TT has received consultant fees from Pfizer and speaker’s honoraria from Eli Lilly, Meiji- Seika Pharma, MSD, Janssen Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Yoshitomi Yakuhin, Mochida Pharmaceutical, Otsuka Pharmaceutical, Kyowa Pharmaceutical, and Takeda Pharmaceutical. KW has received manuscript fees or speaker’s honoraria from Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Yoshitomi Yakuhin, has received research/grant support from Daiichi Sankyo, Eisai, MSD, Mitsubishi Tanabe Pharma, Meiji Seika Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and is a consultant for Boehringer Ingelheim, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Pharmaceutical, Lundbeck Japan, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, and Viatris. NY-F has received grant/research support or honoraria from, and received speaker’s honoraria of Dainippon-Sumitomo Pharma, Mochida Pharmaceutical, MSD, and Otsuka Pharmaceutical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tokumitsu, Sugawara, Adachi, Kubota, Watanabe, Miki, Azekawa, Edagawa, Katsumoto, Hongo, Goto, Ueda, Kato, Yoshimura, Nakagawa, Kikuchi, Tsuboi, Watanabe and Yasui-Furukori.)

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., Competing Interests: MK has received grant funding from the Japanese Ministry of Health, Labor and Welfare, the Japan Society for the Promotion of Science, SENSHIN Medical Research Foundation, the Japan Research Foundation for Clinical Pharmacology, and the Japanese Society of Clinical Neuropsychopharmacology and speaker’s honoraria from Sumitomo Dainippon Pharma, Otsuka, Meiji-Seika Pharma, Eli Lilly, MSD K.K., Pfizer, Janssen Pharmaceutical, Shionogi, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Lundbeck, and Ono Pharmaceutical, and participated in an advisory/review board for Otsuka, Sumitomo Dainippon Pharma, Shionogi, and Boehringer Ingelheim. YK has received consultant fees from Pfizer and Meiji-Seika Pharma and speaker’s honoraria from Meiji-Seika Pharma, MSD, Eli Lilly, Janssen Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Yoshitomi Yakuhin, Otsuka Pharmaceutical, Takeda Pharmaceutical, Lundbeck Japan, and Eisai. TA has received speaker’s honoraria from Eli Lilly, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma and Eisai. HU has received manuscript fees or speaker’s honoraria from Eisai Co., Ltd., Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Dainippon Sumitomo Pharma, Takeda Pharmaceutical, Lundbeck Japan, and Yoshitomi Yakuhin. KE has received speaker’s honoraria from Eli Lilly, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Kyowa, Yoshitomi Yakuhin, and Takeda Pharmaceutical. EK has received speaker’s honoraria from Daiichi Sankyo, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, UCB, and Viatris. SH has received manuscript fees or speaker’s honoraria from Eli Lilly, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Yoshitomi Yakuhin. EG has received manuscript fees or speaker’s honoraria from Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Takeda Pharmaceutical, Eisai, Ono Pharmaceutical, Kyowa Pharmaceutical Industry, and Sumitomo Dainippon Pharma. RY has received speaker’s honoraria from Eli Lilly, Dainippon Sumitomo, Otsuka, and Esai. AN has received speaker’s honoraria from Pfizer, Eli Lilly, Otsuka, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida, Dainippon Sumitomo, and NTT Docomo, and participated in an advisory board for Takeda, Meiji Seika, Tsumura, and Yoshitomi Yakuhin. TKik has received consultant fees from Takeda Pharmaceutical and the Center for Cognitive Behavioral Therapy and Training. TT has received consultant fees from Pfizer and speaker’s honoraria from Eli Lilly, Meiji-Seika Pharma, MSD, Janssen Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Yoshitomi Yakuhin, Mochida Pharmaceutical, Otsuka Pharmaceutical, Kyowa Pharmaceutical, and Takeda Pharmaceutical. KW has received manuscript fees or speaker’s honoraria from Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Yoshitomi Yakuhin, has received research/grant support from Daiichi Sankyo, Eisai, MSD, Mitsubishi Tanabe Pharma, Meiji Seika Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and is a consultant for Boehringer Ingelheim, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Pharmaceutical, Lundbeck Japan, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, and Viatris. NY-F has received grant/research support or honoraria from, and received speaker’s honoraria of Dainippon-Sumitomo Pharma, Mochida Pharmaceutical, MSD, and Otsuka Pharmaceutical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Takano, Kato, Adachi, Kubota, Azekawa, Ueda, Edagawa, Katsumoto, Goto, Hongo, Miki, Tsuboi, Yasui-Furukori, Nakagawa, Kikuchi, Watanabe, Kinoshita and Yoshimura.)

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., Competing Interests: YK has received consultant fees from Pfizer and Meiji-Seika Pharma and speaker's honoraria from Meiji-Seika Pharma, MSD, Eli Lilly, Janssen Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Yoshitomi Yakuhin, Otsuka Pharmaceutical, Takeda Pharmaceutical, Lundbeck Japan, and Eisai. TA has received speaker's honoraria from Eli Lilly, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, and Eisai. HU has received manuscript fees or speaker's honoraria from Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Kyowa Pharmaceutical, Shionogi, Lundbeck Japan, and Yoshitomi Yakuhin. KE has received speaker's honoraria from Eli Lilly, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Kyowa, Yoshitomi Yakuhin, and Takeda Pharmaceutical. EK has received speaker's honoraria from Daiichi Sankyo, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, UCB, and Viatris. SH has received manuscript fees or speaker's honoraria from Eli Lilly, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Yoshitomi Yakuhin. EG has received manuscript fees or speaker's honoraria from Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Takeda Pharmaceutical, Eisai, Ono Pharmaceutical, Kyowa Pharmaceutical Industry, and Sumitomo Dainippon Pharma. MK has received grant funding from the Japanese Ministry of Health, Labor and Welfare, the Japan Society for the Pro- motion of Science, SENSHIN Medical Research Foundation, the Japan Research Foundation for Clinical Pharmacology and the Japanese Society of Clinical Neuropsychopharmacology and speaker's honoraria from Sumitomo Dainippon Pharma, Otsuka, Meiji-Seika Pharma, Eli Lilly, MSD K.K., Pfizer, Janssen Pharmaceutical, Shionogi, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Lundbeck and Ono Pharmaceutical and participated in an advisory/review board for Otsuka, Sumitomo Dainippon Pharma, Shionogi and Boehringer Ingelheim. RY has received speaker's honoraria from Eli Lilly, Dainippon Sumitomo, Otsuka, and Esai. AN has received speaker's honoraria from Pfizer, Eli Lilly, Otsuka, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida, Dainippon Sumitomo and NTT Docomo, and participated in an advisory board for Takeda, Meiji Seika, Tsumura and Yoshitomi Yakuhin. TK has received consultant fees from Takeda Pharmaceutical and the Center for Cognitive Behavioral Therapy and Training. TT has received consultant fees from Pfizer and speaker's honoraria from Eli Lilly, Meiji- Seika Pharma, MSD, Janssen Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Yoshitomi Yakuhin, Mochida Pharmaceutical, Otsuka Pharmaceutical, Kyowa Pharmaceutical, and Takeda Pharmaceutical. KW has received manuscript fees or speaker's honoraria from Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Kyowa Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Yoshitomi Yakuhin, has received research/grant support from Daiichi Sankyo, Eisai, MSD, Mitsubishi Tanabe Pharma, Meiji Seika Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and is a consultant for Boehringer Ingelheim, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Pharmaceutical, Lundbeck Japan, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, and Viatris. KS has received research support from Novartis Pharma, Dainippon Sumitomo Pharma, Astellas Pharma, Meiji Seika Pharma, Eisai, Pfizer, Otsuka Pharmaceutical, Daiichi Sankyo, and Takeda Pharmaceutical and honoraria from Eisai, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Meiji Seika Pharma, Janssen Pharmaceutical, Shionogi, Dainippon Sumitomo Pharma, Daiichi Sankyo, and Pfizer. NY-F has received grant/research support or honoraria from, and received speaker's honoraria of Dainippon-Sumitomo Pharma, Mochida Pharmaceutical, MSD, and Otsuka Pharmaceutical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tokumitsu, Yasui-Furukori, Adachi, Kubota, Watanabe, Miki, Azekawa, Edagawa, Katsumoto, Hongo, Goto, Ueda, Kato, Nakagawa, Kikuchi, Tsuboi, Watanabe, Shimoda and Yoshimura.)