Diagnostic and prognostic significance of tartrate-resistant acid phosphatase type 5b in newly diagnosed prostate cancer with bone metastasis: A real-world multi-institutional study.

OBJECTIVES: Approximately, 90% of men with advanced prostate cancer will develop bone metastasis. However, there have been few reports about noninvasive biomarker to detect and predict clinical outcome of bone metastasis (BM) in prostate cancer patients. METHODS: We examined 1127 patients who underwent prostate biopsy from August 2012 to June 2017. We also investigated bone turnover markers such as bone-specific alkaline phosphatase, type I collagen cross-linked N-terminal telopeptide, C-terminal pyridinoline cross-linked telopeptide of type I collagen, and tartrate-resistant acid phosphatase type 5b (TRACP 5b). RESULTS: A total of 282 patients were diagnosed as prostate cancer with complete clinical data, and 34 patients with bone metastasis. Multivariate analysis revealed C-terminal pyridinoline cross-linked telopeptide of type I collagen, tartrate-resistant acid phosphatase type 5b, and prostate-specific antigen (PSA) were independent biomarkers in detection of BM (p < 0.05, respectively). Furthermore, we developed predictive model formula based on tartrate-resistant acid phosphatase type 5b and PSA, for which the area under the curve was 0.95. In patients with bone metastasis, multivariate cox proportional hazards analysis revealed that this model was significantly associated with poor clinical outcome of cancer-specific survival (p < 0.05). In validation cohort with 137 patients, we also confirmed the utility of this model for diagnosis of BM (the area under the curve = 0.95). CONCLUSIONS: Our developed formula of tartrate-resistant acid phosphatase type 5b in accordance with PSA may serve as the useful tool in diagnosis and prediction of clinical outcome for prostate cancer with bone metastasis.

Application of the Unified Protocol for a Japanese Patient with Post-Traumatic Stress Disorder and Multiple Comorbidities: A Single-Case Study.

(1) Background: The efficacy of the Unified Protocol (UP), a transdiagnostic cognitive-behavioral therapy, with trauma-focused exposure has not been sufficiently demonstrated for post-traumatic stress disorder (PTSD) with multiple comorbidities. This study examined the effects of UP treatment with trauma-focused exposure on symptoms of PTSD and comorbidities in a client who was hesitant about exposure. (2) Methods: The client, who had comorbid dysthymia, social anxiety disorder, agoraphobia, and bulimia nervosa, participated in the UP for 20 sessions over 6 months. The principal diagnosis and symptoms of the comorbid disorders were assessed at baseline, post-intervention, and at the 3-month follow-up. This treatment was conducted as part of a clinical study (UMIN000008322). (3) Results: The client showed improvement in the principal diagnosis and symptoms of the comorbid disorders post-intervention compared with baseline and no longer met the diagnostic criteria for any of the disorders. Considerable symptom improvement was observed with imaginal exposure to trauma memories. (4) Conclusions: The UP was an effective alternative treatment for PTSD and symptoms of comorbidities in this client who was hesitant about exposure to traumatic memories, and that the inclusion of trauma-focused exposure provided sufficient therapeutic effects. Further research is needed to examine the generalizability of our findings.

Cost-effectiveness analyses of augmented cognitive behavioral therapy for pharmacotherapy-resistant depression at secondary mental health care settings.

AIM: Pharmacotherapy is the primary treatment strategy in major depression. However, two-thirds of patients remain depressed after the initial antidepressant treatment. Augmented cognitive behavioral therapy (CBT) for pharmacotherapy-resistant depression in primary mental health care settings proved effective and cost-effective. Although we reported the clinical effectiveness of augmented CBT in secondary mental health care, its cost-effectiveness has not been evaluated. Therefore, we aimed to compare the cost-effectiveness of augmented CBT adjunctive to treatment as usual (TAU) and TAU alone for pharmacotherapy-resistant depression at secondary mental health care settings. METHODS: We performed a cost-effectiveness analysis at 64 weeks, alongside a randomized controlled trial involving 80 patients who sought depression treatment at a university hospital and psychiatric hospital (one each). The cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) that compared the difference in costs and quality-adjusted life years, and other clinical scales, between the groups. RESULTS: The ICERs were JPY -15 278 322 and 2 026 865 for pharmacotherapy-resistant depression for all samples and those with moderate/severe symptoms at baseline, respectively. The acceptability curve demonstrates a 0.221 and 0.701 probability of the augmented CBT being cost-effective for all samples and moderate/severe depression, respectively, at the threshold of JPY 4.57 million (GBP 30 000). The sensitivity analysis supported the robustness of our results restricting for moderate/severe depression. CONCLUSION: Augmented CBT for pharmacotherapy-resistant depression is not cost-effective for all samples including mild depression. In contrast, it appeared to be cost-effective for the patients currently manifesting moderate/severe symptoms under secondary mental health care.

Age-Related Changes in Item Responses to the Patient Health Questionnaire-9: Evidence From the National Health and Nutrition Examination Survey.

BACKGROUND: Epidemiological studies have shown that total scores in depression screening scales change with age, but the mechanism underlying these age-related changes remains unclear. Previous research has indicated that item responses in depression screening scales exhibit characteristic distributions in the general population. We analyzed Patient Health Questionnaire-9 (PHQ-9) data from a representative survey conducted in the USA, to determine how the response pattern for each item changed with age and whether the pattern of responses contributed to age-related changes in total scores. METHODS: We analyzed PHQ-9 data for 17,274 participants in the 2011-2016 National Health and Nutrition Examination Survey. The PHQ-9 allows respondents to self-rate the frequency of depressive symptoms using a four-point scale ranging from "not at all" to "nearly every day". RESULTS: The lines for all nine item responses followed the same characteristic pattern across all age groups, which was marked by intersection at a single point between "not at all" and "several days" and parallel patterns between "several days" and "nearly every day" on a logarithmic scale. The probability of "nearly every day" showed a reverse U-shaped pattern, in that it was low from 12-29 years, increased during 30-50 years, and then decreased at ≥60 years. The age-related change in the probability of a response of "nearly every day" coincided with the trajectory of the PHQ-9 total scores. CONCLUSIONS: This study demonstrated that item responses for the PHQ-9 followed a similar mathematical pattern across the adult lifespan. Moreover, our findings suggested that the probability of a response of "nearly every day" played an important role in age-related changes in PHQ-9 total scores across adulthood.

[A Case of Brain, Lung, and Adrenal Metastasis from Colorectal Cancer Controlled by Loco-Regional Surgery].

A 64-year-old man presented with the chief complaint of weakness in the left half of his body. He fell down on the road while riding a bicycle and was transported to the emergency room. A contrast-enhanced brain MRI revealed a 28mm ringshaped mass in the right frontal lobe. A craniotomy was performed 14 days later. The histopathological diagnosis showed the tumor as a well-differentiated tubular adenocarcinoma. Postoperative examination revealed a rectal cancer and a left lung mass. A low-anterior resection was performed 1 month after the craniotomy, and a partial lung resection was performed 2 months after the rectal excision. Metachronous solitary metastasis of the left adrenal gland was noticed 10 months after the removal of the lung metastasis and we subsequently performed a left adrenalectomy. The patient is not undergoing any active treatment 13 months after the adrenalectomy, but has no signs of recurrence. The loco-regional surgery was enabled for local control of multi-relapsed lesions from rectal cancer.

Responses to depressive symptom items exhibit a common mathematical pattern across the European populations.

The theoretical distribution of responses to depressive symptom items in a general population remains unknown. Recent studies have shown that responses to depressive symptom items follow the same pattern in the US and Japanese populations, but the degree to which these findings can be generalized to other countries is unknown. The purpose of this study was to conduct a pattern analysis on the EU population's responses to depressive symptom items using data from the Eurobarometer. The Eurobarometer questionnaires include six depressive symptom items from the 12-item General Health Questionnaire. The pattern analysis revealed that, across the entire EU population, the ratios between "score = 2" and "score = 1" and between "score = 3" to "score = 2" were similar among the six items and resulted in a common pattern. This common pattern was characterized by an intersection at a single point between "score = 0" and "score = 1" and a parallel pattern between "score = 1" and "score = 3" on a logarithmic scale. Country-by-country analyses revealed that the item responses followed a common characteristic pattern across all 15 countries. Our results suggest that responses to depressive symptom items in a general population follow the same characteristic pattern regardless of the specific country.

Distribution of psychological distress is stable in recent decades and follows an exponential pattern in the US population.

The prevalence of psychological distress is fairly stable in industrialised countries in recent decades, but the reasons for this stability remain unknown. To investigate the mechanisms underlying stability of psychological distress in the general population of the United States, we analysed the mathematical patterns of the distribution of psychological distress in recent decades. The present study utilised the Kessler psychological distress scale (K6) data from the 1997‒2017 United States National Health Interview Survey. We used overlap coefficients and graphical analysis to investigate the stability and mathematical patterns of the K6 distribution. Overlap coefficients and graphical analysis demonstrated that the distribution of K6 total scores was stable in the United States over the past two decades. Furthermore, the distributions of K6 total scores exhibited an exponential pattern, with the exception of the lower end of the distribution. These findings suggest that the lack of change in the prevalence of psychological distress over several decades is due to the stability of psychological distress distribution itself. Furthermore, the stability of the distribution of psychological distress over time may be linked to the exponential pattern of psychological distress distribution.

Further evidence that item responses on the Kessler Psychological Distress Scale exhibit the characteristic pattern in the general population.

BACKGROUND: Previous studies suggested that item responses on the 6-item Kessler Psychological Distress Scale (K6) exhibit characteristic distributions among the general population. To confirm the reproducibility of these findings, we conducted a pattern analysis of the K6 item responses using large-scale data from a US representative survey. METHODS: Data were drawn from the 2016, and 2017 National Health Interview Survey in the United States (33,028, and 26,742 individuals, respectively). We analyzed the patterns of item responses for the six items using normal and logarithmic scales and proposed a model of item responses. RESULTS: The lines for item responses showed the same pattern among the six items, characterized by crossing at a single point between "none" and "a little," and parallel patterns from "a little" to "all of the time" on a logarithmic scale. The ratio of "some" to "a little," "most" to "some," and "most" to "all of the time" were similar across the six items. The model of item responses, which was based on the findings that the decreasing ratios of "some" to "a little," "most" to "some," and "all of the time" to "most" were similar across the six items, explained the characteristic patterns of item responses. CONCLUSION: These results provide further evidence that item responses on the K6 follow a particular distribution pattern among the general population.

School mental healthcare services using internet-based cognitive behaviour therapy for young male athletes in Japan.

AIM: Preventive intervention and treatment using internet-based cognitive behaviour therapy (iCBT) can be easily administered to school students, as they are quite familiar with internet tools. This study aims to investigate the effectiveness and contribution of iCBT to mental healthcare in a school setting. METHODS: Eighty Japanese high school boys who were participating in a sports specialist course were enrolled in this study. The participants were randomly assigned to either the iCBT intervention group or the control group. Both programmes were administered for 4 weeks. To evaluate the effects, physical and mental health problems and self-efficacy were assessed. RESULTS: The mean number of times that the iCBT website was accessed during the intervention period was 16.9, and the mean access frequency (percentage of the number of times the website was accessed during the intervention period) was 40.1% in the iCBT group. A statistically significant interaction between group and time in favour of the iCBT group was observed based on the Kessler-6 (K6) scale for depression and anxiety. CONCLUSIONS: The results suggest that a school mental healthcare programme using iCBT is suitable for students and useful for coping with stress and reducing depressed mood and anxiety in young people, especially athletes, who are regarded as needing special mental health support.

Web-Based Cognitive Behavioral Therapy Blended With Face-to-Face Sessions for Major Depression: Randomized Controlled Trial.

BACKGROUND: Meta-analyses of several randomized controlled trials have shown that cognitive behavioral therapy (CBT) has comparable efficacy to antidepressant medication, but therapist availability and cost-effectiveness is a problem. OBJECTIVE: This study aimed to evaluate the effectiveness of Web-based CBT blended with face-to-face sessions that reduce therapist time in patients with major depression who were unresponsive to antidepressant medications. METHODS: A 12-week, assessor-masked, parallel-group, waiting- list controlled, randomized trial was conducted at 3 medical institutions in Tokyo. Outpatients aged 20-65 years with a primary diagnosis of major depression who were taking ≥1 antidepressant medications at an adequate dose for ≥6 weeks and had a 17-item GRID-Hamilton Depression Rating Scale (HAMD) score of ≥14 were randomly assigned (1:1) to blended CBT or waiting-list groups using a computer allocation system, stratified by the study site with the minimization method, to balance age and baseline GRID-HAMD score. The CBT intervention was given in a combined format, comprising a Web-based program and 12 45-minute face-to-face sessions. Thus, across 12 weeks, a participant could receive up to 540 minutes of contact with a therapist, which is approximately two-thirds of the therapist contact time provided in the conventional CBT protocol, which typically provides 16 50-minute sessions. The primary outcome was the alleviation of depressive symptoms, as measured by a change in the total GRID-HAMD score from baseline (at randomization) to posttreatment (at 12 weeks). Moreover, in an exploratory analysis, we investigated whether the expected positive effects of the intervention were sustained during follow-up, 3 months after the posttreatment assessment. Analyses were performed on an intention-to-treat basis, and the primary outcome was analyzed using a mixed-effects model for repeated measures. RESULTS: We randomized 40 participants to either blended CBT (n=20) or waiting-list (n=20) groups. All patients completed the 12-week treatment protocol and were included in the intention-to-treat analyses. Participants in the blended CBT group had significantly alleviated depressive symptoms at week 12, as shown by greater least squares mean changes in the GRID-HAMD score, than those in the waiting list group (-8.9 points vs -3.0 points; mean between-group difference=-5.95; 95% CI -9.53 to -2.37; P<.001). The follow-up effects within the blended CBT group, as measured by the GRID-HAMD score, were sustained at the 3-month follow-up (week 24) and posttreatment (week 12): posttreatment, 9.4 (SD 5.2), versus follow-up, 7.2 (SD 5.7); P=.009. CONCLUSIONS: Although our findings warrant confirmation in larger and longer term studies with active controls, these suggest that a combined form of CBT is effective in reducing depressive symptoms in patients with major depression who are unresponsive to antidepressant medications. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009242; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010852 (Archived by WebCite at http://www.webcitation. org/729VkpyYL).

Stability of the Distribution of Patient Health Questionnaire-9 Scores Against Age in the General Population: Data From the National Health and Nutrition Examination Survey.

Background: Epidemiological studies using the nine-item Patient Health Questionnaire (PHQ-9) have reported inconsistencies regarding the relationship between age and total scores. To determine whether this discrepancy is due to the stability of the distribution of PHQ-9 total scores against age, we investigated whether the total score distribution remains stable during adulthood, and also investigated the mathematical patterns of the total score distribution. Methods: The present study utilized data from 15,847 participants of the 2009-2014 United States National Health and Nutrition Examination Survey, all of whom responded to all PHQ-9 items. The stability of the total score distribution among different age groups was examined using overlap coefficients and graphical analysis. Results: High overlap coefficients were observed between all age groups for the distributions of PHQ-9 total scores, suggesting that the distribution of PHQ-9 total scores remains stable against age. Graphical analysis demonstrated that distributions of PHQ-9 total scores were similar across age groups. In addition, distributions of PHQ-9 total scores exhibited an exponential pattern, except at the lower end of the distribution. Conclusions: Our findings indicate that the stability of the distribution of PHQ-9 total scores throughout adulthood may underlie inconsistencies in the evidence regarding age-related changes in total depression scores.

Distribution of item responses and total item scores for the Center for Epidemiologic Studies Depression Scale (CES-D): Data from the Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Previous studies have shown that item responses and total scores on depression screening scales follow characteristic distribution patterns in the United States and Japanese general populations. However, the degree to which these findings, especially in terms of item responses, can be generalized to a European population is unknown. Thus, we analyzed the item responses and total score distribution for the Center for Epidemiologic Studies Depression Scale (CES-D) in a representative Irish cohort from a large, recent study-the Irish Longitudinal Study on Ageing (TILDA). METHODS: We used CES-D data from the 2009-2011 TILDA (8504 individuals). Responses for the 16 depressive symptoms included "rarely," "some of the time," "occasionally," and "all of the time." Item response patterns and total score distribution across these 16 depressive symptom items were examined using graphical analyses and exponential regression modeling. RESULTS: Lines for item responses followed the same pattern across the 16 items. These lines were characterized by intersections in the vicinity of a single point between "rarely" and "some of the time" and parallel patterns from "some of the time" to "all of the time" on a log-normal scale. Total scores for the 16 items exhibited an exponential pattern, except for at the lower end of the distribution. CONCLUSIONS: The present findings suggest that item responses and total scores on depression screening scales among the general population follow the same characteristic patterns across populations from multiple nations.

Distributional patterns of item responses and total scores on the PHQ-9 in the general population: data from the National Health and Nutrition Examination Survey.

BACKGROUND: Recently, item responses and total scores on depression screening scales have been reported to have characteristic distributions in the general population. The distributional pattern of responses to the Patient Health Questionnaire-9 (PHQ-9) in the general population has not been well studied. Thus, we carried out a pattern analysis of the PHQ-9 item responses and total scores in US adults. METHODS: Data (5372 individuals) were drawn from the 2013-2014 National Health and Nutrition Examination Survey in the United States. The item responses and total score distributions of the PHQ-9 data were investigated with graphical analysis and exponential regression model. RESULTS: Lines of item responses showed the same pattern among the nine items, characterized by crossing at a single point between "not at all" and "several days" and a parallel pattern from "several days" to "nearly every day" on a log-normal scale. The total score distribution of the PHQ-9 exhibited an exponential pattern, except for at the lower end of the distribution. CONCLUSIONS: The present results support that the item responses and total scores on the PHQ-9 in the general population show the same characteristic patterns, consistent with the previous studies using the Center for Epidemiologic Studies Depression Scale (CES-D) and Kessler Screening Scale for Psychological Distress (K6).

Civilians in World War II and DSM-IV mental disorders: results from the World Mental Health Survey Initiative.

PURPOSE: Understanding the effects of war on mental disorders is important for developing effective post-conflict recovery policies and programs. The current study uses cross-sectional, retrospectively reported data collected as part of the World Mental Health (WMH) Survey Initiative to examine the associations of being a civilian in a war zone/region of terror in World War II with a range of DSM-IV mental disorders. METHODS: Adults (n = 3370) who lived in countries directly involved in World War II in Europe and Japan were administered structured diagnostic interviews of lifetime DSM-IV mental disorders. The associations of war-related traumas with subsequent disorder onset-persistence were assessed with discrete-time survival analysis (lifetime prevalence) and conditional logistic regression (12-month prevalence). RESULTS: Respondents who were civilians in a war zone/region of terror had higher lifetime risks than other respondents of major depressive disorder (MDD; OR 1.5, 95% CI 1.1, 1.9) and anxiety disorder (OR 1.5, 95% CI 1.1, 2.0). The association of war exposure with MDD was strongest in the early years after the war, whereas the association with anxiety disorders increased over time. Among lifetime cases, war exposure was associated with lower past year risk of anxiety disorders (OR 0.4, 95% CI 0.2, 0.7). CONCLUSIONS: Exposure to war in World War II was associated with higher lifetime risk of some mental disorders. Whether comparable patterns will be found among civilians living through more recent wars remains to be seen, but should be recognized as a possibility by those projecting future needs for treatment of mental disorders.

[A Case of Polyarteritis Nodosa Diagnosed from Pathological Findings of Refractory Epididymitis].

A 54-year-old man was admitted to internal medicine due to unidentified fever persisting for 3 months, and was examined. Then, he was referred to our department for suspected pyelonephritis. Although he was initially being treated for pyelonephritis, right epididymitis occurred during the course of treatment. Antibiotics were ineffective, and symptoms such as weakness and subctaneous nodules also appeared. We performed epididymectomy to differentiate this intractable epididymitis from other systemic diseases. Pathological findings were fibrinoid necrotic vasculitis of middle and small arteries. Of the diagnostic criteria for polyarteritis nodosa, 4 major symptoms and histological findings were satisfied. After we started oral administration of predonin, the fever went down and the creative protein level decreased immediatately.

[A Case of Fulminant Hepatitis after Administration of Abiraterone Acetate].

A 77-year-old man with castration-resistant prostate cancer (CRPC) received abiraterone acetate in October 2014. He visited our outpatient clinic because of general malaise and anorexia 27 days after starting abiraterone acetate. The lab test showed hepatic dysfunction (aspartate transaminase, AST 440 U/l, alanine transaminase, ALT 420 U/l) and the elevation of liver enzymes continued on the next day even after stopping abiraterone acetate. Three days later, he was hospitalized due to severe elevation of liver enzymes (AST 1,171 U/l, ALT 1,487 U/l) , and the decreased prothrombin activity (60.5%). The result of the lab test were negative for viral and autoimmune hepatitis. Three days after admission, he entered hepatic coma (grade III) and prothrombin activity decreased (23.2%) , compatible with fulminant hepatitis. Plasma exchange and steroid pulse therapy were started the next day, but he died 39 days after starting abiraterone acetate. In addition, the result of drug-induced lymphocyte stimulation test performed 3 days before his death was possibly positive.

[A Case of Castration-Resistant Prostate Cancer with Fatal Convulsive Seizure after Administration of Enzalutamide].

Enzalutamide, an androgen receptor antagonist, is a standard drug for the treatment of castrationresistant prostate cancer. A 77-year-old man developed a seizure after administration of enzalutamide. The patient presented with general fatigue and high fever approximately 5 weeks after oral administration of enzalutamide. Several days later, a seizure attack occurred at home, resulting in cardiopulmonary arrest. The patient was taken to the hospital emergency room but could not be resuscitated. We described a 63-year-old man who was diagnosed with clinical T1c prostate cancer, with a Gleason score of 6 (3＋3), and a preoperative prostate-specific antigen (PSA) level of 5. 27 ng/ml. Radical prostatectomy(RP) was performed and final pathologyshowed Gleason score 3＋4, pT2c with negative surgical margin. In spite of suggested surgical radicality, PSA was 3.32, 4.78, 5.93 ng/ml, at 1, 2, and 3 months after RP, respectively. However, radiological investigation revealed no metastasis. Because of this clinical discrepancy, we checked the PSA-α1-antichemotrypsin level and found it to be ≦0.1 ng/ml. From these results, false PSA elevation caused byinterference of positive heterophilic antibodies was suggested and demonstrated byseveral immunoassays.

Characteristic distribution of the total and individual item scores on the Kessler Screening Scale for Psychological Distress (K6) in US adults.

BACKGROUND: The distributional pattern of total scores on depression screening scales in the general population has not been well studied. Recent studies suggest that the total scores on depression screening scales follow an exponential pattern, with the exception of the lower end of the distribution. To further investigate the findings, we determined the distributions of the total and individual item scores on the Kessler Screening Scale for Psychological Distress (K6). METHODS: Data were obtained from the National Survey of Midlife Development in the United States. Participants comprised 6,223 individuals between the ages of 25 and 74. The distributions of the total and individual item scores in various combinations were investigated with histograms and regression analysis. RESULTS: Irrespective of the combination of items, the total and individual item scores followed an exponential pattern except at the lower scores. The estimated rate parameters of regression analysis were similar among distributions with the same number of chosen items. At the lower scores, the distributional patterns of total scores varied according to the ratio of "a little" to "none" for each item response. CONCLUSIONS: The present results have the potential to estimate the distribution of depressive symptoms in the general population. While the degree of depressive symptoms varies from individual to individual, an entire population may show a certain mathematical distribution.

Effectiveness of Supplementary Cognitive-Behavioral Therapy for Pharmacotherapy-Resistant Depression: A Randomized Controlled Trial.

OBJECTIVE: Antidepressant medication is efficacious in the treatment of depression, but not all patients improve with antidepressant medication alone. Despite this treatment gap, limited evidence regarding the effectiveness of supplementing psychotherapy for pharmacotherapy-resistant depression is available. Therefore, we investigated the effectiveness of supplementing usual medication management (treatment as usual [TAU]) with cognitive-behavioral therapy (CBT) in patients with pharmacotherapy-resistant depression seeking psychiatric specialty care. METHODS: A 16-week assessor-masked randomized controlled trial with a 12-month follow-up was conducted in 1 university hospital and 1 psychiatric hospital from September 2008 to December 2014. Outpatients aged 20-65 years with pharmacotherapy-resistant depression (taking antidepressant medications for ≥ 8 weeks, 17-item GRID-Hamilton Depression Rating Scale [GRID-HDRS17] score ≥ 16, Maudsley Staging Method for treatment-resistant depression score ≥ 3, and DSM-IV criteria for major depressive disorder) were randomly assigned (1:1) to CBT combined with TAU or to TAU alone. The primary outcome was the alleviation of depressive symptoms, as measured by change in the total GRID-HDRS17 score from baseline to 16 weeks; primary analysis was done on an intention-to-treat basis. RESULTS: A total of 80 patients were randomized; 78 (97.5%) were assessed for the primary outcome, and 73 (91.3%) were followed up for 12 months. Supplementary CBT significantly alleviated depressive symptoms at 16 weeks, as shown by greater least squares mean changes in GRID-HDRS17 scores in the intervention group than in the control group (-12.7 vs -7.4; difference = -5.4; 95% CI, -8.1 to -2.6; P < .001), and the treatment effect was maintained for at least 12 months (-15.4 vs -11.0; difference = -4.4; 95% CI, -7.2 to -1.6; P = .002). CONCLUSIONS: Patients with pharmacotherapy-resistant depression treated in psychiatric specialty care settings may benefit from supplementing usual medication management with CBT. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000001218​​.

Relationship between Item Responses of Negative Affect Items and the Distribution of the Sum of the Item Scores in the General Population.

BACKGROUND: Several studies have shown that total depressive symptom scores in the general population approximate an exponential pattern, except for the lower end of the distribution. The Center for Epidemiologic Studies Depression Scale (CES-D) consists of 20 items, each of which may take on four scores: "rarely," "some," "occasionally," and "most of the time." Recently, we reported that the item responses for 16 negative affect items commonly exhibit exponential patterns, except for the level of "rarely," leading us to hypothesize that the item responses at the level of "rarely" may be related to the non-exponential pattern typical of the lower end of the distribution. To verify this hypothesis, we investigated how the item responses contribute to the distribution of the sum of the item scores. METHODS: Data collected from 21,040 subjects who had completed the CES-D questionnaire as part of a Japanese national survey were analyzed. To assess the item responses of negative affect items, we used a parameter r, which denotes the ratio of "rarely" to "some" in each item response. The distributions of the sum of negative affect items in various combinations were analyzed using log-normal scales and curve fitting. RESULTS: The sum of the item scores approximated an exponential pattern regardless of the combination of items, whereas, at the lower end of the distributions, there was a clear divergence between the actual data and the predicted exponential pattern. At the lower end of the distributions, the sum of the item scores with high values of r exhibited higher scores compared to those predicted from the exponential pattern, whereas the sum of the item scores with low values of r exhibited lower scores compared to those predicted. CONCLUSIONS: The distributional pattern of the sum of the item scores could be predicted from the item responses of such items.