Gender Differences in Premenstrual Syndrome and Premenstrual Dysphoric Disorder Diagnosis and Treatment among Japanese Obstetricians and Gynecologists: A Cross-Sectional Study.

Premenstrual symptoms are characterized by unpleasant psychophysical symptoms that appear during the luteal phase before menstruation and interfere with a woman's quality of life. Premenstrual syndrome (PMS) is a pathological condition with premenstrual symptoms, of which premenstrual dysphoric disorder (PMDD) is a particularly severe psychological symptom. This study aimed to examine the gender differences in the diagnosis and treatment of PMS and PMDD among obstetricians and gynecologists (OB/GYNs) in Japan. Data were obtained from the survey conducted by the Japanese Society of Obstetrics and Gynecology. We used data from 1,257 of the 1,265 OB/GYNs who are engaged in PMS/PMDD practice and reported their gender. Multivariate regression analysis adjusted for propensity scores was performed. Female OB/GYNs were more frequently engaged in treating patients with PMS/PMDD than males [odds ratio (OR) 1.74; 95% confidence interval (CI) 1.36-2.21]. With regard to the diagnostic methods, more female OB/GYNs selected the two-cycle symptom diary than males (OR 2.88; 95% CI 1.80-4.60). Regarding treatment, fewer female OB/GYNs selected selective serotonin reuptake inhibitors as their first-line drug (OR 0.39; 95% CI 0.17-0.89). Gender differences were found in the selection of PMS/PMDD diagnosis and treatment methods among Japanese OB/GYNs.

Current status and problems in the diagnosis and treatment of premenstrual syndrome and premenstrual dysphoric disorder from the perspective of obstetricians and gynecologists in Japan.

AIM: To investigate the current status and problems in the diagnosis and treatment of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) from the perspective of obstetricians and gynecologists (OB/GYNs) in Japan, the Japanese Society of Obstetrics and Gynecology (JSOG) conducted a national-wide survey. METHODS: An email survey was sent to all JSOG members (16 732) and a web-based survey was conducted using a Google form between September and November 2021. The current status and problems in PMS/PMDD diagnosis and treatment were surveyed in this cross-sectional study. RESULTS: In total, 1312 respondents (7.8% of all JSOG members) completed the questionnaire. In terms of diagnoses and treatment, OB/GYN was preferred over psychiatrist for PMS (91.4% vs. 45%); however, no differences were noted for PMDD (76.1% vs. 73.7%). A total of 1267 (96.6%) respondents engaged in routine PMS/PMDD treatment. Regarding the general diagnosis procedure, 84.4% respondents answered "only a vague medical interview," 8.4% kept a two-cycle symptom diary, and 10.3% used a screening questionnaire. The most commonly used medication was oral contraceptive pills (OCPs) (98.1%), followed by the Kampo, traditional Japanese herbal medicines, Kamishoyosan (73.6%). Concerning first-line drugs for treatment, OCPs were the most common (76.8%), followed by Kampo medicine (19.5%); selective serotonin reuptake inhibitors (SSRIs) were less frequently used (2.6%). Regarding first-line drugs among OCPs, 65.1% respondents reported drospirenone-ethinylestradriol use. CONCLUSIONS: This study indicates that only a few OB/GYNs practicing PMS/PMDD in Japan use a prospective diary, which is an essential diagnostic criterion for PMS/PMDD. Regarding treatment, SSRIs were used less frequently.

Does cognitive behavioral therapy for anxiety disorders assist the discontinuation of benzodiazepines among patients with anxiety disorders? A systematic review and meta-analysis.

Long-term use of benzodiazepines (BZD) is not recommended for the treatment of anxiety disorders. Cognitive behavioral therapy (CBT) is an effective treatment option for discontinuation of BZD in patients with anxiety disorders. This systematic review and meta-analysis sought to clarify whether CBT is effective for discontinuing BZD anxiolytics in patients with anxiety disorders. This study was preregistered with PROSPERO (registration number: CRD42019125263). A literature search of major electronic databases was conducted in December 2018. Three randomized controlled trials were included in this review, and meta-analyses were performed. The proportion of discontinuing BZD anxiolytics was significantly higher in the CBT plus gradual tapering group than in the gradual tapering alone group, both in the short term (3 months after allocation; number needed to treat: 3.2, 95% confidence interval [CI]: 2.1 to 7.1; risk ratio: 1.96, 95%CI: 1.29 to 2.98, P = 0.002, three studies) and long term (6 to 12 months after allocation; number needed to treat: 2.8, 95%CI: 1.9 to 5.3; risk ratio: 2.16, 95%CI: 1.41 to 3.32, P = 0.0004, three studies). CBT may be effective for discontinuing BZD anxiolytics, both in the short term and in the long term after the allocation. Further studies with larger sample sizes are necessary to draw definitive conclusions regarding the efficacy and safety of CBT for discontinuing BZD anxiolytics in patients with anxiety disorders.

How significant is the assessment of the DSM-5 'anxious distress' specifier in patients with major depressive disorder without comorbid anxiety disorders in the continuation/maintenance phase?

OBJECTIVE: Anxious distress (ANXD), which is common in major depressive disorder (MDD), is associated with poor outcomes. We investigated clinical characteristics of MDD patients with the DSM-5 ANXD specifier and only mild residual symptoms without comorbid anxiety disorders in the continuation/maintenance phase. METHODS: We recruited 110 outpatients with MDD without comorbid anxiety disorders. They were interviewed; the presence of the DSM-5 ANXD specifier was assessed. They completed the Quick Inventory of Depressive Symptomatology (QIDS), the Eysenck Personality Questionnaire (S-EPQ), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). RESULTS: The mean QIDS total score was 9.7 ± 5.5. The DSM-5 ANXD specifier was identified in 73 patients (66.4%). A univariate analysis indicated ANXD was significantly associated with younger age; unmarried status; living alone; higher QIDS total score; higher S-EPQ neuroticism score; and higher TEMPS-A cyclothymic, depressive and irritable scores. After covariate adjustment, a multivariable linear regression analysis revealed a significant association between the QIDS total score and ANXD (three different models). CONCLUSION: The DSM-5 ANXD was also common among MDD patients without comorbid anxiety disorders in the continuation/maintenance phase; it was significantly associated with greater depression severity and might be related to temperament associated with bipolar disorder.Key pointsDSM-5 anxious distress is common among MDD patients without comorbid anxiety disorders in the continuation/maintenance phase and correlated with some of their socio-demographic and clinical characteristics. • The presence of DSM-5 anxious distress was significantly associated with greater severity of depression and might be related to temperament associated with bipolar disorder.• The evaluation of the DSM-5 anxiety distress was revealed to have some significance not only in the acute phase but also in the continuation/maintenance phase of MDD.

[The Relationship between Generalized Anxiety Disorder and Depression, and Its Countermeasures].

Generalized, persistent, and free-floating anxiety was first described by Freud in 1894. The diagnostic term generalized anxiety disorder (GAD) was not in classification systems until the publication of the diagnostic and statistical manual for mental disorders, third edition (DSM-III) in 1980. Initially considered a residual category to be used when no other diagnosis could be made. The term GAD is not accepted as a distinct diagnostic category yet. Since 1980, revisions to the diagnostic criteria for GAD in the DSM-III-R, DSM-IV and DSM-5 classifica- tions have slightly redefined this disorder. The classification is fluid. This article reviews the development of diagnostic criteria for defining GAD from Freud to DSM-5. Excessive worry- ing impairs the individual's capacity to do things quickly and efficiently, whether at home or at work. The worrying takes time and energy; associated symptoms of feeling keyed up or edge, tiredness, difficulty concentrating, and depression. Individuals whose presentation meets crite- ria for GAD are likely to have met, or currently meet, criteria for unipolar depressive disor- ders. Comorbid depression are common in GAD and negatively impact treatment outcome.

The incremental burden of pain in patients with depression: results of a Japanese survey.

BACKGROUND: Major depressive disorder (MDD) is a chronic mental illness which affects an estimated 3% of the Japanese population. Many patients with MDD report painful physical symptoms, and research outside of Japan suggests such patients may represent a subtype of depression which is more severe and difficult to treat. There is no evidence available about the characteristics or incremental burden of these patients in Japan. The objective of this study was to quantify the incremental burden of physical pain among individuals in Japan diagnosed with depression. METHODS: Data for individuals age 18 and older who reported a physician diagnosis of depression were obtained from the Japan National Health and Wellness Survey (NHWS). Respondents who also reported physical pain were matched to respondents who did not report pain using propensity scores and compared using bivariate statistics. Measures included Patient Health Questionnaire (PHQ-9) for depression severity, Medical Outcomes Study 12-Item Short Form Survey Instrument (SF-12v2) for health-related quality of life, the Work Productivity and Activity Impairment (WPAI) for work and activity impairment, and 6-month report of health care use. RESULTS: Individuals with depression who reported physical pain had higher PHQ-9 depression scores (14.3 vs. 11.1, p<0.001), lower health-related quality of life (Mental Component Summary score [MCS] 29.1 vs. 32.0, p<0.01; Physical Component Summary score [PCS] 43.0 vs. 47.2, p<0.001; health utility [SF-6D] 0.567 vs. 0.613, p<0.001), more presenteeism (46.3% vs. 36.8%, p<0.01), more overall work impairment (51.4% vs. 42.3%, p<0.01), more activity impairment (55.4% vs. 43.9%, p<0.001), and reported using more health care provider visits in the prior 6 months (17.7 vs. 12.8, p<0.01) as well as hospitalizations (1.7 vs. 0.8, p<0.05) relative to propensity-score matched controls without pain. Absenteeism (13.1% vs. 11.4%, p=0.51) and emergency room visits (0.31 vs. 0.35, p=0.76) were not significantly different between the two matched groups. CONCLUSIONS: Individuals whose depression is accompanied by physical pain have a higher burden of illness than those whose depression does not include physical pain. Clinicians should take the presence of pain into account and consider treating both the physical and emotional symptoms of these patients.

Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study.

AIM: Results from this randomized, placebo-controlled study of aripiprazole augmentation to antidepressant therapy (ADT) in Japanese patients with major depressive disorder (MDD) (the Aripiprazole Depression Multicenter Efficacy [ADMIRE] study) revealed that aripiprazole augmentation was superior to ADT alone and was well tolerated. In subgroup analyses, we investigated the influence of demographic- and disease-related factors on the observed responses. We also examined how individual symptom improvement was related to overall improvement in MDD. METHODS: Data from the ADMIRE study were analyzed. Subgroup analyses were performed on the primary outcome measures: the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) treatment to the end of the randomized treatment. RESULTS: Changes in the MADRS total scores were consistently greater with aripiprazole than placebo in each of the subgroups. Efficacy was not related to sex, age, number of adequate ADT trials in the current episode, MDD diagnosis, number of depressive episodes, duration of the current episode, age at first depressive episode, time since the first depressive episode, type of SSRI/SNRI, or severity at the end of SSRI/SNRI treatment phase. Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS items, including sadness. CONCLUSION: These post-hoc analyses indicated that aripiprazole was effective for a variety of Japanese patients with MDD who had exhibited inadequate responses to ADT. Additionally, we suggest that aripiprazole significantly and rapidly improved the core depressive symptoms.

Prevalence of Generalized Anxiety Disorder in Japan: A General Population Survey.

Purpose: 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.

Diagnosis and Treatment of Generalized Anxiety Disorder in Japan: Psychiatric Specialist Survey.

Purpose: 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.

Feasibility of remote interviews in assessing disease severity in patients with major depressive disorder: A pilot study.

AIM: Interview quality is an important factor in the success of clinical trials for major depressive disorder (MDD). There is a substantial need to establish a reliable, remote clinical assessment interview system that can replace traditional in-person interviews. METHODS: We conducted a multicenter, randomized, unblinded, prospective, cross-sectional study to assess the reliability of remote interviews in patients with MDD (UMIN000041839). Eligible patients with MDD underwent remote and in-person sessions of the Montgomery-Åsberg Depression Rating Scale (MADRS) assessment performed by different raters within 28 days of providing consent. Patients were randomized to a group first assessed using in-person interviews and secondarily using remote interviews (in-person-first group) or a group first assessed by remote interviews and secondarily using in-person interviews (remote-first group). Nineteen trained people (15 clinical psychologists, 3 nurses, and 1 clinical laboratory technologist) performed interviews. RESULTS: Of 59 patients (in-person-first group, n = 32; remote-first group, n = 27) who completed both remote and in-person interviews, 51% (n = 30) were women; the mean age was 41.6 years (range, 21-64 years). There was a strong association between remote and in-person MADRS scores (r = 0.891, kappa = 0.901). An overall intraclass correlation coefficient (ICC) of 0.886 (95% confidence interval, 0.877-0.952) indicated good consistency between MADRS scores in remote and in-person interviews. The ICC decreased as the severity of depression increased. CONCLUSION: Our results suggest remote interviews are a feasible alternative option to in-person interviews in assessing symptom severity in MDD patients and could promote clinical trials in Japan.

Development and acceptability of a decision aid for anxiety disorder considering discontinuation of benzodiazepine anxiolytic.

Aim: We aimed to develop a decision aid (DA) for individuals with anxiety disorders who consider tapering benzodiazepine (BZD) anxiolytics, and if tapering, tapering BZD anxiolytics with or without cognitive behavioral therapy (CBT) for anxiety. We also assessed its acceptability among stakeholders. Methods: First, we conducted a literature review regarding anxiety disorders to determine treatment options. We cited the results of the systematic review and meta-analysis, which we conducted previously, to describe the related outcomes of two options: tapering BZD anxiolytics with CBT and tapering BZD anxiolytics without CBT. Second, we developed a DA prototype in accordance with the International Patient Decision Aid Standards. We carried out a mixed methods survey to assess the acceptability among stakeholders including those with anxiety disorders and healthcare providers. Results: Our DA provided information such as explanation of anxiety disorders, options of tapering or not tapering BZD anxiolytics (if tapering, the options of tapering BZD anxiolytics with or without CBT) for anxiety disorder, benefits and risks of each option, and a worksheet for value clarification. For patients (n = 21), the DA appeared to be acceptable language (86%), adequate information (81%), and well-balanced presentation (86%). The developed DA was also acceptable for healthcare providers (n = 10). Conclusion: We successfully created a DA for individuals with anxiety disorders who consider tapering BZD anxiolytics, which was acceptable for both patients and healthcare providers. Our DA was designed to assist patients and healthcare providers to involve decision-making about whether to taper BZD anxiolytics or not.

[How to use psychotropic medicine in women].

It's very important to know how to use psychotropic medicine, especially selective serotonin reuptake inhibitors in pregnant women. Because between 14% and 23% of pregnant women will experience a depressive disorder while pregnant. In 2003, approximately 13% of women took an antidepressant at some point in pregnancy, a rate that has doubled since 1999. Both maternal depressive symptoms and antidepressant exposure are associated with fetal growth changes and shorter gestations, but the majority of studies that evaluated antidepressant risks were unable to control for the possible effects of a depressive disorder. Antidepressant use in pregnancy is well studied, but available research has not yet adequately controlled for other factors that may influence birth outcomes including maternal illness or problematic health behaviors that can adversely affect pregnancy.

[Generalized anxiety disorder, now and the future: a perspective to the DSM-5].

Generalized, persistent, and free-floating anxiety was first described by Freud in 1894. The diagnostic term generalized anxiety disorder (GAD) was not in classification systems until the publication of the diagnostic and statistical manual for mental disorders, third edition (DSM-III) in 1980. Initially considered as a residual category to be used when no other diagnosis could be made, it is not accepted that GAD represents a distinct diagnostic category yet. Since 1980, revisions to the diagnostic criteria for GAD in the DSM-III-R, DSM-IV and DSM-5 classifications have slightly redefined this disorder. The classification is fluid. The duration criterion has increased to 6 months in DSM-IV, but decreased to 3 months in DSM-5. This article reviews the development of diagnostic criteria for defining GAD from Freud to DSM-5 and compares the DSM-5 criterion with DSM-IV and the tenth revision of the International Classification of Disease. The impact of the changes in diagnostic criteria on research into GAD, and on diagnosis, differential diagnosis, will be discussed.

Psychological Effects on Healthcare Workers during the COVID-19 Outbreak: A Single-center Study at a Tertiary Hospital in Tokyo, Japan.

Objective The present study analyzed the psychological status of healthcare workers in Japan and the influencing factors during the 2019 coronavirus disease pandemic. Methods An online survey was conducted from July 22 to August 21, 2020. A total of 328 of the 1,029 medical staff members in our university hospital participated in the study. Their mental health was assessed using the 12-item General Health Questionnaire. A multivariate regression analysis was performed to identify the factors associated with the mental health outcomes. Results Of the respondents, 78.0% reported psychological distress. Overall, we found that women, non-physicians, those who lived alone, and younger respondents had significantly greater psychological distress than their counterparts. The multivariate regression analysis showed that four factors were extracted as independent 12-item General Health Questionnaire-related factors: the lack of a sense of mission as a medical professional, the burden of the change in the quality of work, the lack of understanding about virus infectivity, and a strong sense of duty. Conclusion In summary, we found a high prevalence of psychological distress among healthcare workers during the 2019 coronavirus disease outbreak in Japan. Independent risk factors for psychological distress were the burden of the change in the quality of work, the lack of understanding about virus infectivity, a sense of responsibility, and the lack of a strong motivation and drive to help.

Obsessive-compulsive disorder and obsessive-compulsive symptoms in Japanese inpatients with chronic schizophrenia - a possible schizophrenic subtype.

To investigate the prevalence of obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS) and their association with demographic and clinical factors, 92 inpatients with chronic schizophrenia participated in this study. Demographic factors, severity of psychiatric symptoms as determined by Brief Psychiatric Rating Scale and OCS by Yale-Brown Obsessive Compulsive Scale, general functioning, extrapyramidal symptoms, and dose of antipsychotics were compared between patients with and without OCD or OCS. The Mini-International Neuropsychiatric Interview was employed for diagnosis of OCD and OCS. OCD and OCS were observed in 14.1% and 51.1% of inpatients with schizophrenia, respectively. Schizophrenic patients with OCS exhibited significantly earlier onset of schizophrenia, lower socioeconomic status, and more severe psychiatric symptoms than those without OCS. Earlier hospitalization of schizophrenia, family history of psychosis, and more severe schizophrenic symptoms were associated with comorbidity of OCS, as determined by logistic regression analysis, and younger age was associated with more severe OCS. However, negative symptoms were associated with comorbidity of OCD in chronic schizophrenia. Our findings suggest there is a subtype of schizophrenia with OCS, which is related to earlier onset and more severe psychotic symptoms.

Brexpiprazole for the Treatment of Schizophrenia in Adults: An Overview of Its Clinical Efficacy and Safety and a Psychiatrist's Perspective.

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.

Analysis of HAM-D scores and working ability in an observational study of Japanese patients with major depressive disorder and painful physical symptoms treated with duloxetine or SSRI monotherapy.

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.

Longitudinal neuroendocrine changes assessed by dexamethasone/CRH and growth hormone releasing hormone tests in psychotic depression.

Although psychotic depression has been reported to exhibit a greater degree of dysregulation of hypothalamic-pituitary-adrenocortical (HPA) function than non-psychotic depression, little is known concerning hypothalamic-pituitary-somatotropic (HPS) function in psychotic depression and how neuroendocrine function changes after treatment. To investigate the longitudinal changes in HPA and HPS system function in psychotic depression, we performed repeated dexamethasone/corticotropin releasing hormone (DEX/CRH) tests and growth hormone (GH) releasing hormone (GHRH) tests in inpatients with major depressive disorder. The psychotic depression group exhibited greater elevation of ACTH responses to the DEX/CRH test and stronger decreases in GH responses to the GHRH test than the non-psychotic depression group at admission. At discharge, the neuroendocrine responses to the DEX/CRH test of the psychotic depression group were still stronger than those of the non-psychotic depression group, though there were no significant differences in severity of depression between the groups. There were significant longitudinal changes in neuroendocrine responses to the DEX/CRH test between admission and discharge. The psychotic depression group exhibited increased GH responses to GHRH at discharge compared with those at admission, whereas no significant longitudinal change in GH response was found in the non-psychotic depression group. Consequently, there were no significant differences in GH responses to GHRH between the psychotic and non-psychotic depression groups at discharge. The results of GHRH test showed no significant relationships with severity of depression except psychotic features and the results of the DEX/CRH test. Our findings suggest that the HPS axis may be associated with psychotic features rather than general severity of depression. Further longitudinal studies are needed to clarify the role of HPS function in psychotic depression and whether sustained dysregulation of HPA function in psychotic depression is associated with a poor outcome after discharge.

Relationships of DEX/CRH and GHRH test results to the outcome of depression--preliminary results suggest the GHRH test may predict relapse after discharge.

To explore and compare hypothalamic-pituitary-somatotropic (HPS) axis function and hypothalamic-pituitary-adrenocortical (HPA) axis function in depression, the dexamethasone (DEX)/CRH test and growth hormone releasing hormone (GHRH) test were prospectively performed on patients with depression at the time of admission and discharge. The patients who relapsed within six months after discharge exhibited significantly lower growth hormone (GH) responses to GHRH at the time of discharge than those who did not relapse. There were no significant correlations between GH response to GHRH and the results of DEX/CRH tests after controlling for age, sex, and body mass index. The findings of this study suggest that results of the GHRH test may be a predictor of future relapse in patients with depression.