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Atsuko Ikenouchi,1,2 Yusuke Konno,1,3 Yoshihisa Fujino,3 Naoto Adachi,4 Yukihisa Kubota,4 Takaharu Azekawa,4 Hitoshi Ueda,4 Koji Edagawa,4 Eiichi Katsumoto,4 Eiichiro Goto,4 Seiji Hongo,4 Masaki Kato,5,6 Takashi Tsuboi,5,7 Norio Yasui-Furukori,5,8 Atsuo Nakagawa,5,9 Toshiaki Kikuchi,5,9 Koichiro Watanabe,5,7 Reiji Yoshimura1,5 1Department of Psychiatry, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; 2Medical Center for Dementia, Hospital of the University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; 3Department of Environmental Epidemiology, Institute of Ecological Sciences, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; 4The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan; 5The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan; 6Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; 7Department of Neuropsychiatry, Kyorin University, Tokyo, Japan; 8Department of Psychiatry, Dokkyo Medical University, Tochigi, Japan; 9Department of Neuropsychiatry, Keio University, Tokyo, JapanCorrespondence: Atsuko Ikenouchi, Department of Psychiatry, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, 807-8555, Japan, Tel +81-93-691-7253, Fax +81-93-692-4894, Email atsuko-i@med.uoeh-u.ac.jpPurpose: 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.Keywords: mood disorder, loss of employment, nationwide study, real world

Takashi Tsuboi,1,2 Takefumi Suzuki,2,3 Takaharu Azekawa,4 Naoto Adachi,4 Hitoshi Ueda,4 Kouji Edagawa,4 Eiichi Katsumoto,4 Yukihisa Kubota,4 Eiichiro Goto,4 Seiji Hongo,4 Yoichiro Watanabe,4 Masaki Kato,2,5 Norio Yasui-Furukori,2,6 Reiji Yoshimura,2,7 Atsuo Nakagawa,2,8 Toshiaki Kikuchi,2,8 Koichiro Watanabe1,2 1Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 2The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan; 3Department of Neuropsychiatry, University of Yamanashi Faculty of Medicine, Yamanashi, Japan; 4The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan; 5Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; 6Department of Psychiatry, Dokkyo Medical University, Tochigi, Japan; 7Department of Psychiatry, University of Occupational and Environmental Health, Fukuoka, Japan; 8Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, JapanCorrespondence: Takashi TsuboiDepartment of Neuropsychiatry, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka-Shi, Tokyo 181-8611, JapanTel +81 422 47 5511Fax +81 422 45 4697Email takashi.tsuboi.0821@gmail.comPurpose: 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.Keywords: bipolar disorder, non-remission, nationwide study, mood stabilizer, antipsychotics

Yusuke Konno,1,2 Yoshihisa Fujino,2 Atsuko Ikenouchi,1,3 Naoto Adachi,4 Yukihisa Kubota,4 Takaharu Azekawa,4 Hitoshi Ueda,4 Koji Edagawa,4 Eiichi Katsumoto,4 Eiichiro Goto,4 Seiji Hongo,4 Masaki Kato,5,6 Takashi Tsuboi,5,7 Norio Yasui-Furukori,5,8 Atsuo Nakagawa,5,9 Toshiaki Kikuchi,5,9 Koichiro Watanabe,5,7 Reiji Yoshimura1,5 1Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan; 2Department of Environmental Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Medical Center for Dementia, University Hospital of Occupational and Environmental Health, Kitakyushu, Japan; 4The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan; 5The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan; 6Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; 7Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 8Department of Psychiatry, Dokkyo Medical University, Tochigi, Japan; 9Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, JapanCorrespondence: Yusuke KonnoDepartment of Psychiatry, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, 807-8555, JapanTel +81-93-691-7401Fax +81-93-692-4894Email yu-konno@med.uoeh-u.ac.jpObjective: 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.Keywords: mood disorder, continuous employment, occupational health, Japan

Tempei Otsubo,1 Yoshinori Watanabe,2,3 Seiji Hongo,3 Mikichika Inoue,4 Kimiko Akimoto,4 Ken Murakami,5 Ryutaro Takahashi,6 Toshiaki Kikuchi7 1Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan; 2Himorogi Psychiatric Institute, Tokyo, Japan; 3Nanko Clinic of Psychiatry, Shirakawa, Japan; 4Ikebukuro Internal Medicine, Tokyo, Japan; 5Murakami Hospital, Tokyo, Japan; 6Takahashi Clinic, Tokyo, Japan; 7Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Aim: To assess the effectiveness and safety of switching the antidepressant formulation from immediate-release (IR) to controlled-release (CR) paroxetine in patients with major depressive disorder (MDD). Patients and methods: A total of 113 outpatients with MDD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and treated with a stable dose of IR paroxetine for at least 6 months were enrolled. Patients were then switched to CR paroxetine for 8 weeks. Effectiveness was evaluated by scores on the Himorogi Self-Rating Depression/Anxiety Scales (HSDS/HSAS) and the Clinical Global Impression – Severity (CGI-S). Safety was evaluated based on the reported adverse drug reactions (ADRs). Medication satisfaction and preference were assessed based on questionnaire responses using Likert-type scales. Results: The overall patient HSDS/HSAS scores significantly improved after switching from IR to CR paroxetine (P

Yoshinori Watanabe,1,2 Seiji Hongo2 1Himorogi Psychiatric Institute, Tokyo, 2Nanko Clinic of Psychiatry, Shirakawa city, Fukushima, Japan Background: We investigated whether the long-term efficacy and safety of lamotrigine (LTG) for bipolar disorder (BP) differs between disease types (BP-I, BP-II, or BP not otherwise specified [BP-NOS]), and the efficacy of the concomitant use of antidepressants (ADs).Methods: For >1 year, we observed 445 outpatients with BP (diagnosed by DSM-IV criteria) who initiated LTG treatment between July 1 and October 31, 2011, using the Himorogi Self-rating Depression (HSDS) and Anxiety Scales and the Clinical Global Impression-Improvement scale and also recorded adverse events.Results: Treatment efficacy was observed at week 4, with the improved HSDS scores sustained until week 52 for all types of BP; 50% of the patients with any type of BP could be treated with LTG for 1 year, whereas ~40% could be treated for >1.5 years. However, 25% of the patients were withdrawn within the first 4 weeks. The overall incidence of adverse events was 22.9% (104/455): 34.1% (14/41) for BP-I, 22.7% (15/66) for BP-II, and 22.2% (75/338) for BP-NOS. The most common adverse event was skin rash: 22.0% for BP-I, 16.7% for BP-II, and 12.1% for BP-NOS.Limitations: There was no control group. Data were collected retrospectively.Conclusion: With careful and adequate titration, long-term treatment with LTG is possible for any type of BP, with BP-NOS patients, the largest population in clinical practice, responding particularly well. Symptoms can improve with or without ADs. Large-scale prospective studies of the efficacy of ADs in bipolar treatment are warranted. Keywords: lamotrigine, bipolar disorder, long-term efficacy, antidepressant, skin rash, anxiety