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Introduction: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). Methods: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. Results: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. Discussion/Conclusion: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

Shortened versions of self-reported questionnaires may be used to reduce respondent burden. When shortened screening tools are used, it is desirable to maintain equivalent diagnostic accuracy to full-length forms. This manuscript presents a case study that illustrates how external data and individual participant data meta-analysis can be used to assess the equivalence in diagnostic accuracy between a shortened and full-length form. This case study compares the Patient Health Questionnaire-9 (PHQ-9) and a 4-item shortened version (PHQ-Dep-4) that was previously developed using optimal test assembly methods. Using a large database of 75 primary studies (34,698 participants, 3,392 major depression cases), we evaluated whether the PHQ-Dep-4 cutoff of ≥ 4 maintained equivalent diagnostic accuracy to a PHQ-9 cutoff of ≥ 10. Using this external validation dataset, a PHQ-Dep-4 cutoff of ≥ 4 maximized the sum of sensitivity and specificity, with a sensitivity of 0.88 (95% CI 0.81, 0.93), 0.68 (95% CI 0.56, 0.78), and 0.80 (95% CI 0.73, 0.85) for the semi-structured, fully structured, and MINI reference standard categories, respectively, and a specificity of 0.79 (95% CI 0.74, 0.83), 0.85 (95% CI 0.78, 0.90), and 0.83 (95% CI 0.80, 0.86) for the semi-structured, fully structured, and MINI reference standard categories, respectively. While equivalence with a PHQ-9 cutoff of ≥ 10 was not established, we found the sensitivity of the PHQ-Dep-4 to be non-inferior to that of the PHQ-9, and the specificity of the PHQ-Dep-4 to be marginally smaller than the PHQ-9.

We examine two studies on the prevalence and comorbidity of anxiety and depressive disorders in Japanese patients in primary care settings. The PRIME-MD study (Primary Care Evaluation of Mental Disorders) in Japan was conducted in seven primary care sites. The sample group included 601 adult patients (249 males, 352 females, mean age = 58.9 years, SD = 16.5). Of the 12.5% of patients diagnosed with mood disorders, 5.0% (n = 29) were major depressive disorder, and 6.7% (n = 40) were minor depressive disorder. The odds ratio for co-occurrence of major depressive disorder with generalized anxiety disorders and major depressive disorder with anxiety disorders (NOS) was 11.5 (95% CI: 2.17–18.45) and 8.00 (95% CI: 3.19–20.07), respectively. The PHQ (Patient Health Questionnaire) study in Japan was conducted in eleven primary care sites. A total of 1409 adult patients (611 males, 797 females; mean age: 56.2 years, SD: ±20.4) completed the PHQ in full. The prevalence of diagnosis of any mood disorder or any anxiety disorder was 25.0%. Of the 15.8% of patients diagnosed with mood disorders, 5.3% were for major depression and 8.4% for other depressive disorders. The odds ratio for co-occurrence of major depressive disorder with other anxiety disorders was 30.4 (95% CI: 13.19–70.28).

Importance The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9. Objective To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression. Data sources MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-May 2018). Study selection Eligible data sets compared PHQ-2 scores with major depression diagnoses from a validated diagnostic interview. Data extraction and synthesis Individual participant data were synthesized with bivariate random-effects meta-analysis to estimate pooled sensitivity and specificity of the PHQ-2 alone among studies using semistructured, fully structured, or Mini International Neuropsychiatric Interview (MINI) diagnostic interviews separately and in combination with the PHQ-9 vs the PHQ-9 alone for studies that used semistructured interviews. The PHQ-2 score ranges from 0 to 6, and the PHQ-9 score ranges from 0 to 27. Results Individual participant data were obtained from 100 of 136 eligible studies (44 318 participants; 4572 with major depression [10%]; mean [SD] age, 49 [17] years; 59% female). Among studies that used semistructured interviews, PHQ-2 sensitivity and specificity (95% CI) were 0.91 (0.88-0.94) and 0.67 (0.64-0.71) for cutoff scores of 2 or greater and 0.72 (0.67-0.77) and 0.85 (0.83-0.87) for cutoff scores of 3 or greater. Sensitivity was significantly greater for semistructured vs fully structured interviews. Specificity was not significantly different across the types of interviews. The area under the receiver operating characteristic curve was 0.88 (0.86-0.89) for semistructured interviews, 0.82 (0.81-0.84) for fully structured interviews, and 0.87 (0.85-0.88) for the MINI. There were no significant subgroup differences. For semistructured interviews, sensitivity for PHQ-2 scores of 2 or greater followed by PHQ-9 scores of 10 or greater (0.82 [0.76-0.86]) was not significantly different than PHQ-9 scores of 10 or greater alone (0.86 [0.80-0.90]); specificity for the combination was significantly but minimally higher (0.87 [0.84-0.89] vs 0.85 [0.82-0.87]). The area under the curve was 0.90 (0.89-0.91). The combination was estimated to reduce the number of participants needing to complete the full PHQ-9 by 57% (56%-58%). Conclusions and relevance In an individual participant data meta-analysis of studies that compared PHQ scores with major depression diagnoses, the combination of PHQ-2 (with cutoff ≥2) followed by PHQ-9 (with cutoff ≥10) had similar sensitivity but higher specificity compared with PHQ-9 cutoff scores of 10 or greater alone. Further research is needed to understand the clinical and research value of this combined approach to screening.

Objectives: Depression symptom questionnaires are not for diagnostic classification. Patient Health Questionnaire-9 (PHQ-9) scores >= 10 are nonetheless often used to estimate depression prevalence. We compared PHQ-9 >= 10 prevalence to Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) major depression prevalence and assessed whether an alternative PHQ-9 cutoff could more accurately estimate prevalence. Study Design and Setting: Individual participant data meta-analysis of datasets comparing PHQ-9 scores to SCID major depression status. Results: A total of 9,242 participants (1,389 SCID major depression cases) from 44 primary studies were included. Pooled PHQ-9 >= 10 prevalence was 24.6% (95% confidence interval [CI]: 20.8%, 28.9%); pooled SCID major depression prevalence was 12.1% (95% CI: 9.6%, 15.2%); and pooled difference was 11.9% (95% CI: 9.3%, 14.6%). The mean study-level PHQ-9 >= 10 to SCID-based prevalence ratio was 2.5 times. PHQ-9 >= 14 and the PHQ-9 diagnostic algorithm provided prevalence closest to SCID major depression prevalence, but study-level prevalence differed from SCID-based prevalence by an average absolute difference of 4.8% for PHQ-9 >= 14 (95% prediction interval: -13.6%, 14.5%) and 5.6% for the PHQ-9 diagnostic algorithm (95% prediction interval: -16.4%, 15.0%). Conclusion: PHQ-9 >= 10 substantially overestimates depression prevalence. There is too much heterogeneity to correct statistically in individual studies. (C) 2020 Elsevier Inc. All rights reserved.

Objective Whether or not depression affects the control or severity of asthma is unclear. We performed a cluster analysis of asthma patients with depressive symptoms to clarify their characteristics. Methods Multiple medical institutions in Niigata Prefecture, Japan, were surveyed in 2014. We recorded the age, disease duration, body mass index (BMI), medications, and surveyed asthma control status and severity, as well as depressive symptoms and adherence to treatment using questionnaires. A hierarchical cluster analysis was performed on the group of patients assessed as having depression. Results Of 2,273 patients, 128 were assessed as being positive for depressive symptoms [DS(+)]. Thirty-three were excluded because of missing data, and the remaining 95 DS[+] patients were classified into 3 clusters (A, B, and C). The patients in cluster A (n=19) were elderly, had severe, poorly controlled asthma, and demonstrated possible adherence barriers; those in cluster B (n=26) were elderly with a low BMI and had no significant adherence barriers but had severe, poorly controlled asthma; and those in cluster C (n=50) were younger, with a high BMI, no significant adherence barriers, well-controlled asthma, and few were severely affected. The scores for depressive symptoms were not significantly different between clusters. Conclusion About half of the patients in the DS[+] group had severe, poorly controlled asthma, and these clusters were able to be distinguished by their Adherence Starts with Knowledge (ASK)-12 score, which reflects adherence barriers. The control status and severity of asthma may also be related to the age, disease duration, and BMI in the DS[+] group.

BackgroundItem 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.MethodsWe conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.Results16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).ConclusionsPHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22–0.24 lower compared to fully structured interviews and 0.06–0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82–0.92) and 0.86 (0.82–0.88). Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.

The Patient Health Questionnaire-9 (PHQ-9) is commonly used to screen for depressive disorder and for monitoring depressive symptoms. However, there are mixed findings regarding its factor structure (i.e., whether it has a unidimensional, two-dimensional, or bi-factor structure). Furthermore, its measurement invariance between non-clinical and clinical populations and that between patients with major depressive disorder (MDD) and MDD with comorbid anxiety disorder (AD) is unknown. Japanese adults with MDD (n = 406), MDD with AD (n = 636), and no psychiatric disorders (non-clinical population; n = 1,163) answered this questionnaire on the Internet. Confirmatory factor analyses showed that the bi-factor model had a better fit than the unidimensional and two-dimensional factor models did. The results of a multi-group confirmatory factor analysis indicated scalar invariance between the non-clinical and only MDD groups, and that between the only MDD and MDD with AD groups. In conclusion, the bi-factor model with two specific factors was supported among the non-clinical, only MDD, and MDD with AD groups. The scalar measurement invariance model was supported between the groups, which indicated the total or sub-scale scores were comparable between groups.

Objective To assess the performance of the Japanese version of the Patient Health Questionnaire-9 (J-PHQ-9) for depression in primary care. Methods Participants in both phases completed the J-PHQ-9, while patients in the second phase also completed the SF-8 (the short form for the health-related QOL scale SF-36). Subjects (n = 284; male = 107, female = 177) had to return the questionnaires to their health care professional within 48 hours and undergo a diagnostic evaluation interview based on the Japanese version of M.I.N.I-Plus. Results 93 patients were diagnosed as having major depressive disorder (MDD). In the J-PHQ-9, the optimal cutpoint ≥ 10 had sensitivity of 90.5% and specificity of 76.6%. As for the categorical algorithms, the sensitivity was 80.6%; specificity was 89.5%, and a positive likelihood ratio of 7.7. The Stratum-specific likelihood ratios (SSLRs) of the J-PHQ-9 scores of 0-9, 10-14, 15-19, and 20-27 for major depression were 0.10 (95% CI: 0.05-0.20), 1.67 (95% CI: 1.02-2.76), 5.41 (95% CI: 2.87-10.22), and 11.98 (95% CI: 5.39-26.63), respectively. The relationship between the severity of J-PHQ-9 and the MCS of SF-8 was significant (χ 2 ＝ 85.72, df = 4, P ≤ 0.0001). Conclusions This study has validated the J-PHQ-9 as a useful tool for the assessment of MDD in primary care in Japan.

Background Depression has been linked to poorer asthma control in asthmatic patients. Although the Japanese version of the Asthma Control Test (ACT-J) is frequently used as a simple, practical evaluation tool in clinical care settings in Japan, knowledge regarding its efficacy for assessing asthma control in asthmatic patients with depression is limited. Thus, we retrospectively investigated cut-off values of the ACT-J for well- controlled asthma, and explored depression's influence on the test with a questionnaire survey. Methods Data were analyzed on 1,962 adult asthmatic patients who had completed both the ACT-J and the Japanese version of the Patient Health Questionnaire-9 (J-PHQ-9) in 2008 questionnaire survey conducted by the Niigata Asthma Treatment Study Group. Patients were classified into low (LD: J-PHQ-9 score of 0-4) or high depression (HD: J-PHQ-9 score of 5-27) groups. In both groups, the efficacy of the ACT-J was confirmed. We then compared the optimal cut-off points for uncontrolled asthma in both groups by performing a receiver operating characteristic (ROC) analysis, using the original classification referred to the GlNA classification as the "true" classification. Results Cronbach's alpha in the LD and HD group was 0.808 and 0.740 respectively. In both groups, the subgroup with existence of work absenteeism or frequent attacks during the previous 12 months scored lower on the ACT-J. The area under the curve and optimal cut-off point for patients with LD and HD were 0.821 and 0.846, and 23 and 20 respectively. Conclusions The efficacy of the ACT-J was confirmed in depressive patients with asthma. Because asthma control as evaluated with the ACT-J can be worse than actual control under depressive states, physicians should also pay attention to a patient's depressive state at evaluation. Further investigations focus on the association between the ACT-J and depression are required.

Objective In Europe and the US, primary care has been anticipated in identifying untreated depression. Findings show a high prevalence of depression in such settings. However, the prevalence of depression in an internal medicine clinic in a rural area of Japan, which has a role in primary care, is unclear. Method The prevalence of depression and comorbid psychiatric disorders among outpatients of an internal medicine clinic in a rural general hospital was measured by a structured interview using the Mini International Neuropsychiatric Interview. Outpatients were recruited consecutively and stratified by Patient Health Questionnaire-9 (PHQ-9) scores. Among 598 outpatients, we interviewed 75 randomly selected patients and 29 whose results of the PHQ-9 were positive. We estimated prevalence of depressive episode using age, sex, physical findings by internal medical doctors and PHQ-9 scores as covariates. Results The estimated prevalence of major and minor depressive episodes were 7.4% [95% confidence interval (CI): 3.4%–11.4%] and 6.8% (95% CI: 2.6%–10.9%), respectively. Among major depressed patients, 71.4% had current suicidal ideation. Conclusion Given the high rate of depression and suicidality, identification of depression and collaboration between internal medical doctors in a rural area of Japan and mental health professionals are needed.

Objective Two depression screening tools, Patient Health Questionnaire (PHQ)-9 and PHQ-2, have not had their validity examined in general internal medicine settings in Japan. We examined the validity of these screening tools. Methods A total of 598 outpatients of an internal medicine clinic in a rural general hospital were enrolled consecutively and stratified by PHQ-9 score. Seventy-five patients randomly selected and 29 patients whose results from the PHQ-9 were considered to be positive for depressive disorder were then interviewed with a semistructured interview, the Mini International Neuropsychiatric Interview. We calculated diagnostic accuracy of the PHQ-9 and PHQ-2 to detect major depression and that of the suicidality item of the PHQ-9 to detect suicidality using sampling weights with multiple imputations. Results Sensitivity and specificity for depression were 0.86 and 0.85, respectively, for the PHQ-9 with cutoff points of 4/5, and 0.77 and 0.95, respectively, for the PHQ-2 with cutoff points of 2/3. Sensitivity and specificity of the suicidality item of the PHQ-9 were 0.70 and 0.97, respectively. Conclusion In internal medicine clinics in Japanese rural hospitals, the PHQ-2 with an optimal cutoff point for each setting plus the suicidality item of the PHQ-9 can be recommended to detect depression without missing suicidality.

Background Previous studies show that depression plays an important role in asthma. However, the association between asthma control and severity, and depression is inconclusive. Methods To investigate the association between asthma control and severity, and depression, we assessed differences in asthma control and asthma severity between groups with various grades of depressive state as defined by the PHQ-9 score using data from the Japanese version of Patient Health Questionnaire-9 (J-PHQ-9) and a questionnaire survey including the Asthma Control Test (ACT). Results The ACT scores in the symptom-screen positive (SP) and major/other depressive disorder (MDD/ ODD) group were significantly lower than those in the symptom-screen negative (SN) and non-MDD/ODD groups, respectively. The rate of step1 and of step 3 and 4 in the SP group were significantly lower and higher than those in the SN group, respectively. When the SP group was divided into three, that is minimal, mild, and more than mild (MTM) depressive state subgroups, the ACT scores in the mild and MTM depressive state subgroups were significantly lower than those in the minimal depressive state subgroup. When the MTM subgroup was divided into moderate, moderate-severe and severe depressive state groups, however, there was no significant variation in ACT score and asthma severity among these three depressive state groups. Conclusions This study is the first, large-scale investigation of the use of the J-PHQ-9 in asthma patients. Using the J-PHQ-9 and the questionnaire, there was a clear association between asthma control and severity, and depression. As the depression became more severe, the existence of other depression-associated factors unrelated to asthma control and severity might be assumed, although further investigation will be required.

Background A general internist has an important role in primary care, especially for the elderly in rural areas of Japan. Although effective intervention models for depressed patients in general practice and primary care settings have been developed in the US and UK medical systems, there is little information regarding even the recognition rate and prescription rate of psychotropic medication by general internists in Japan. The present study surveyed these data cross-sectionally in a general internal medicine outpatient clinic of a Japanese rural hospital. Methods Patients were consecutively recruited and evaluated for major depressive disorder or any mood disorder using the Patient Health Questionnaire (PHQ). Physicians who were blinded to the results of the PHQ were asked to diagnose whether the patients had any mental disorders, and if so, whether they had mood disorders or not. Data regarding prescription of psychotropic medicines were collected from medical records. Results Among 312 patients, 27 (8.7%) and 52 (16.7%) were identified with major depressive disorder and any mood disorder using the PHQ, respectively. Among those with major depressive disorder, 21 (77.8%) were recognized by physicians as having a mental disorder, but only three (11.1%) were diagnosed as having a mood disorder. Only two patients with major depressive disorder (7.4%) had been prescribed antidepressants. Even among those (n = 15) whom physicians diagnosed with a mood disorder irrespective of the PHQ results, only four (26.7%) were prescribed an antidepressant. Conclusions Despite a high prevalence of depression, physicians did not often recognize depression in patients. In addition, most patients who were diagnosed by physicians as having a mood disorder were not prescribed antidepressants. Multiple barriers to providing appropriate care for depressed patients exist, such as recognizing depression, prescribing appropriate medications, and appropriately referring patients to mental health specialists.