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Satoshi Matsuyama,1 Tempei Otsubo,2 Keisuke Nomoto,1 Shingo Higa,1 Osamu Takashio3 1Medical Affairs, Viatris Pharmaceuticals Japan Inc., Tokyo, Japan; 2Department of Psychosomatic and Psychiatric Medicine, Tokyo Women’s Medical University Adachi Medical Center, Tokyo, Japan; 3Department of Neuropsychiatry, Showa University East Hospital, Tokyo, JapanCorrespondence: Satoshi Matsuyama, Medical Affairs, Viatris Pharmaceuticals Japan Inc., Holland Hills Mori Tower, 5-11-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan, Tel +81-3-5656-0400, Fax +81-3-5656-0603, Email satoshi.matsuyama@viatris.comPurpose: Generalized anxiety disorder (GAD) is among the most prevalent and highly disabling mental health conditions that negatively impacts patient’s quality of life (QOL) and disrupts activities of daily living. However, the recognition of GAD is difficult due to substantial overlap with other mental disorders. The purpose of this study was to estimate the prevalence of GAD, assess QOL of probable GAD patients in Japan, and gain insights on the status of visiting medical institutions as well as their recognition/awareness of the disorder.Patients and Methods: We conducted a web-based cross-sectional survey of 20,009 participants using a questionnaire with approximately 30 single/multiple choice or open-ended questions in Japanese.Results: Overall prevalence of GAD based on Generalized Anxiety Disorder 7-item (GAD-7) cutoff score of ≥ 10 and questionnaires developed with reference to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria was 7.6% (n=1530) and 6.0% (n=1197), respectively. The degree of coincidence between GAD diagnosis by DSM-5 criteria and GAD-7 scores was moderate (Cohen’s Kappa=0.47, p< 0.01). Younger people reported a substantially higher prevalence of GAD compared to older. QOL scores assessed using EuroQol 5 dimensions 5-level and EuroQol Visual Analog Scale were substantially lower in probable GAD patients than those with GAD-7< 10. Anxiety/depression and pain/discomfort were the most prevalent issues and depression was the most reported comorbidity for the probable GAD patients. Probable GAD patients “currently visiting medical institutions” for anxiety or other mental issues were 27.6% (422/1530); a majority had seen specialists. Most of the probable GAD patients had never heard of the disease.Conclusion: We found higher prevalence of GAD and lower QOL of probable GAD patients in Japan. There is a need for creating awareness about GAD among the general population and developing clinical guidelines on GAD in Japan so that physicians can educate their patients.Keywords: GAD-7, generalized anxiety disorder, Japan, prevalence, quality of life

Keisuke Nomoto,1 Osamu Takashio,2 Satoshi Matsuyama,1 Shingo Higa,1 Tempei Otsubo3 1Medical Affairs, Viatris Pharmaceuticals Japan Inc., Tokyo, Japan; 2Department of Neuropsychiatry, Showa University East Hospital, Tokyo, Japan; 3Department of Psychosomatic and Psychiatric Medicine, Tokyo Women’s Medical University Adachi Medical Center, Tokyo, JapanCorrespondence: Keisuke Nomoto, Medical Affairs, Viatris Pharmaceuticals Japan Inc., Holland Hills Mori Tower, 5-11-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan, Tel +81-3-5656-0400, Fax +81-3-5656-0603, Email keisuke.nomoto@viatris.comPurpose: Generalized anxiety disorder (GAD) is a suboptimally managed chronic recurring psychiatric condition with a lifetime prevalence of 2.6% in Japan. We assessed the current status of GAD management in Japan.Patients and Methods: This was an observational, cross-sectional study conducted through an anonymous web-based survey in Japan from December 12– 16, 2022. Psychiatrists and psychosomatic medicine physicians who agreed to participate and saw ≥ 10 outpatients in the previous month were eligible. Survey questionnaire comprised 37 single/multiple choice, numerical entry, or open-ended questions in Japanese.Results: Among 509 participants (493 psychiatrists and 16 psychosomatic medicine physicians), 96.9% were aware of GAD. On average, 12.4 outpatients and 1.0 inpatient were diagnosed with GAD per physician per month. Of 433 physicians having patients diagnosed with GAD, 46.9% used operational diagnostic tools; among these, DSM-5 diagnostic criteria were used by 81.5% physicians. The majority (54.7%) of participants did not use a self-administered rating scale; depression scales were used more than anxiety scales. Among these 433 physicians, 96.8% used selective serotonin reuptake inhibitors for GAD management, and 79.2% used it as the first choice; of 431 physicians who prescribed drug therapy, 54.3% gave antidepressant monotherapy as first choice. The most frequent symptom in patients diagnosed with GAD was excessive anxiety/worry (96.5%); depression was the most commonly reported comorbidity (84.3%) as per physicians aware of GAD (N=508).Conclusion: This study illustrates that although GAD awareness is high among Japanese psychiatric specialists, GAD is not frequently diagnosed using operational diagnostic approaches. Due to a lack of Japanese guidelines for GAD diagnosis and treatment, diverse international guidelines are followed, with similar treatment paradigms as that of depression. This may not be an optimal approach given cultural/geographical differences. These findings highlight the need for uniform diagnosis and treatment recommendations for GAD management in Japan.Clinical Trial Registration: UMIN-CTR: UMIN000049572.Keywords: anxiety, GAD, psychiatrist, psychosomatic medicine physician, survey

Yoshinori Watanabe,1 Sakiko Yamada,2 Tempei Otsubo,3 Toshiaki Kikuchi4 1Himorogi Psychiatric Institute, Tokyo, Japan; 2Medical Affairs, Otsuka Pharmaceutical Co. Ltd, Tokyo, Japan; 3Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan; 4Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, JapanCorrespondence: Yoshinori WatanabeHimorogi Psychiatric Institute, 2-31-2 Ichigayatamachi, Shinjuku-ku, Tokyo 162-0843, JapanTel +81-3-5946-8586Email watanabe@himorogi.orgAbstract: While the prognosis of patients with schizophrenia has dramatically improved after the advent of chlorpromazine, the antipsychotics currently available are so numerous that it has become a challenge for psychiatrists to choose from among these drugs for each patient presenting for care. In addition, while numerous studies show that an effective antipsychotic should be continued indefinitely to prevent relapses or worsening, many patients appear to have difficulty remaining on any drug thus initiated. Brexpiprazole, a dopamine D2 receptor partial agonist, appears to provide a unique profile that has much to offer in this light. Specifically, this novel drug is potentially better suited for long-term use, with decreased risk of extrapyramidal side effects, hyperprolactinemia, weight gain, psychosis, insomnia, akathisia, nausea/vomiting or restlessness, thus potentially facilitating patients’ reintegration into society. Indeed, brexpiprazole has been shown in randomized, double-blind, placebo-controlled trials to have proven efficacy not only in improving the symptoms of schizophrenia but in preventing relapses. It is also suggested in both short- and long-term studies that brexpiprazole offers a favorable safety and tolerability profile. This review also includes a proposed treatment algorithm incorporating brexpiprazole, based on the clinical trial results available, as well as on the authors’ clinical experience, where brexpiprazole may be best used as a drug of first choice for the treatment of schizophrenia. Thus, overall, brexpiprazole appears to play a more significant role in the treatment of schizophrenia than other antipsychotics.Keywords: brexpiprazole, dopamine D2 receptor partial agonist, efficacy, safety, schizophrenia, treatment algorithm

Atsushi Kuga,1,* Tempei Otsubo,2,* Toshinaga Tsuji,3 Shinji Hayashi,3 Hideyuki Imagawa,1 Shinji Fujikoshi,1 Rodrigo Escobar4 1Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 2Department of Psychiatry, Tokyo Women’s Medical University, Medical Center East, Tokyo, Japan; 3Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan; 4Bio-Medicines Global Team, Eli Lilly and Company, Madrid, Spain *These authors contributed equally to this work Objective: To investigate the relationship between Hamilton Depression Rating Scale (HAM-D) score and psychiatrists’ judgment of working ability in patients with major depressive disorder (MDD) and painful physical symptoms.Methods: This was a prospective, observational, 12-week study in patients who received duloxetine or a selective serotonin reuptake inhibitor. Patients were ≥20 years old, resided in Japan, and had at least moderate depression (Quick Inventory of Depressive Symptomatology ≥16) and at least moderate painful physical symptoms (Brief Pain Inventory-Short Form average pain ≥3). The main outcome in this post-hoc analysis was the HAM-D17 cutoff best corresponding with patients’ working ability according to the investigator’s judgment. Area under the receiver-operator curve was used to determine the time point with the strongest relationship between HAM-D17 and working ability. The optimal HAM-D17 cutoff was determined based on the maximum of sensitivity (true positive rate) minus ([1 minus specificity] [true negative rate]). For the evaluation of binary data, a mixed effects model with repeated measures analysis was used.Results: For the estimation of the HAM-D17 cutoff, the area under the receiver-operator curve was maximal at 12 weeks, when a HAM-D17 score of 6 resulted in the best correspondence with working ability in the combined study population. At 12 weeks, a HAM-D17 score of 6 also resulted in the maximum predictive ability in each of the two treatment groups separately. For predicted working ability at 12 weeks, 52.7% of duloxetine-treated patients achieved the HAM-D17 cutoff of ≤6, whereas 48.5% of SSRIs-treated patients achieved HAM-D17 ≤6 (P=0.477).Conclusion: In this study of patients with major depressive disorder and painful physical symptoms, a HAM-D17 score ≤6 corresponded best with patients’ working ability. This finding is consistent with previous studies showing that a HAM-D17 cutoff of ≤7 may overestimate functional recovery from MDD. Keywords: functional recovery, reinstatement, remission

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

Jeffrey Vietri,1 Tempei Otsubo,2 William Montgomery,3 Toshinaga Tsuji,4 Eiji Harada5 1Health Outcomes Practice, Kantar Health, Milan, Italy; 2Tokyo Shinjuku Medical Center, Tokyo, Japan; 3Eli Lilly Australia Pty Ltd., West Ryde, Australia; 4Medical Affairs, Shionogi & Co., Ltd., Osaka, Japan; 5Eli Lilly Japan KK, Kobe, Japan Background: Depression is often associated with painful physical symptoms. Previous research has seldom assessed the relationship between the severity of physical symptoms and the severity of mental and emotional symptoms of depression or other health outcomes, and no such studies have been conducted previously among individuals with depression in Japan. The aim of this study was to assess the relationship between the severity of physical pain and depression and other outcomes among individuals in Japan diagnosed with depression.Methods: Data for individuals aged 18 and older in Japan who reported being diagnosed with depression and also reported physical pain were obtained from the Japan National Health and Wellness Survey. These respondents were characterized on sociodemographics and health characteristics, and the relationship between ratings of severity on pain in the last week and health outcomes were assessed using bivariate correlations and generalized linear models. Measures included the Patient Health Questionnaire for depression severity, Medical Outcomes Study 12-Item Short Form Survey Instrument for health-related quality of life, the Work Productivity and Activity Impairment for work and activity impairment, and 6-month report of health care use.Results: More severe physical pain in the past week was correlated with more severe depression, worse health-related quality of life, lower health utility, greater impairment at work, and more health care provider visits. These relationships remained significant after incorporating sociodemographics and health characteristics in the statistical models.Conclusion: Individuals whose depression is accompanied by more severe physical pain have a higher burden of illness than those whose depression includes less severe pain, suggesting that even partially ameliorating painful physical symptoms may significantly benefit patients with depression. Clinicians should take the presence and severity of physical pain into account and consider treating both the physical and emotional symptoms of these patients. Keywords: painful physical symptoms, quality of life, work impairment, health care use