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psychotics have fewer extrapyramidal symptoms through a variety of mechanisms, but it is still unclear why some atypical antipsychotics are effec-tive for depressive states in bipolar disorder and others are not. Olanzapine, quetiapine, and lurasi-done, which are atypical antipsychotics effective for depression in bipolar disorder, all are antago-nists of serotonin receptors, which may be involved in their mechanism of action.Cognitive-behavioral therapy is a treatment that normalizes the cognitive patterns that predispose to depression, such as overgeneralization and all- or-nothing thinking. These characteristic cognitive patterns are the very characteristic information processing of emotions, and cognitive behavioral therapy may normalize the emotion/cognition balance. Currently, lithium, antiepileptic drugs, atyp-ical antipsychotics, and cognitive-behavioral therapy are often used in combination in clinical situations, and they are thought to act at different points in the pathophysiological pathway of bipolar disorder.AcknowledgmentsThis work was partly supported by AMED (JP 20km0405208, JP20dm0207074, 21wm0425006h0001) and JSPS KAKENHI (JP18H05435, JP18H05428).No funding to declare.Author contributionsTK. wrote the manuscript.Conflicts of interest statementDr. Kato reports grants and personal fees from Japan Agency for Medical Research and Develop-ment (AMED), grants and personal fees from Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promo-tion of Science (JSPS), during the conduct of the study; personal fees from Kyowa Hakko Kirin Co., Ltd., personal fees from Eli Lilly Japan K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from GlaxoSmithKline K.K., personal fees from Taisho Pharma Co., Ltd., grants and personal fees from Dainippon Sumitomo Pharma Co., Ltd., personal fees from Meiji Seika Pharma Co., Ltd., personal fees from Pfizer Japan Inc., personal fees from Mochida Pharmaceutical Co., Ltd., grants and personal fees from Shionogi & Co., Ltd., personal fees from Janssen Pharmaceu-tical K.K., personal fees from Janssen Asia Pacific, personal fees from Yoshitomiyakuhin, personal fees from Astellas Pharma Inc., personal fees from Nippon Boehringer Ingelheim Co. Ltd., personal fees from MSD K.K., personal fees from Kyowa Pharmaceutical Industry Co., Ltd., grants and personal fees from Takeda Pharmaceutical Co., Ltd., personal fees from Taisho Pharmaceutical Co., Ltd., personal fees from Taisho Toyama Pharma-ceutical Co., Ltd., grants and personal fees from Eisai Co., Ltd., grants and personal fees from Mitsubishi Tanabe Pharma Corporation, grants from Teijin Pharma, outside the submitted work. 1) Goodwin FK, Jamison KKR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. Second Edition.: Oxford University Press; 2007. 2) Hayes JF, Miles J, Walters K, King M, Osborn DP: A systematic review and meta-analysis of premature mortality in bipolar affective disorder. Acta Psychiatr Scand. 2015; 131: 417-25. 3) Ishikawa H, Tachimori H, Takeshima T, et al: Preva-lence, treatment, and the correlates of common mental disorders in the mid 2010’s in Japan: The results of the world mental health Japan 2nd survey. J Affect Disord. 2018; 241: 554-62. 4) Ishikawa H, Kawakami N, Kessler RC, World Mental Health Japan Survey C: Lifetime and 12-month preva-lence, severity and unmet need for treatment of common mental disorders in Japan: results from the final dataset of World Mental Health Japan Survey. Epidemiol Psychiatr Sci. 2016; 25: 217-29. 5) Kato T, Baba K, Guo W, Chen Y, Nosaka T: Impact of bipolar disorder on health-related quality of life and work productivity: Estimates from the national health and wellness survey in Japan. J Affect Disord. 2021; 295: 203-14. 6) Angst J, Azorin JM, Bowden CL, et al: Prevalence and characteristics of undiagnosed bipolar disorders in patients with a major depressive episode: the BRIDGE study. Arch Gen Psychiatry. 2011; 68: 791-8. 7) American_Psychiatric_Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5: Amer Psychiatric Pub Inc; 2013. 8) Freedman R, Lewis DA, Michels R, et al: The initial field trials of DSM-5: new blooms and old thorns. Am J Psychiatry. 2013; 170: 1-5. 9) Ratheesh A, Davey C, Hetrick S, et al: A systematic review and meta-analysis of prospective transition from major depression to bipolar disorder. Acta Psychiatr Scand. 2017; 135: 273-84.10. Kato T, Sakai N, Watanabe Y, Nomura S: Possibility of over-diagnosis of bipolar disorder due to near-infrared spectroscopy. Psychiatry Clin Neurosci. 2017; 71: 843.11) Kato T: Current understanding of bipolar disorder: Toward integration of biological basis and treatment 23FundingReference