Risk of major depressive disorder in adolescent and young adult cancer patients in Japan.

OBJECTIVE: To estimate the risk of major depressive disorder (MDD) in adolescent and young adult (AYA) patients with cancer in Japan and identify risk factors for MDD among these patients. METHODS: This was a matched cohort study using a large claims database in Japan. Included patients were aged 15-39 years, newly diagnosed with cancer during 2012-2017 and assessable for a follow-up period of 12 months. Kaplan-Meier estimates and Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for MDD in the AYA patients with cancer versus age-, sex- and working status-matched cancer-free controls. A subgroups analysis of the AYA patients with cancer was performed to explore MDD risk factors. RESULTS: A total of 3559 AYA patients with cancer and 35,590 matched controls were included in the analysis. Adolescent and young adult patients with cancer had a three-fold higher risk for MDD compared with cancer-free controls (HR, 3.12; 95% CI, 2.64-3.70). Among cancer categories with >100 patients, patients with multiple cancer categories, including those with metastatic cancer (HR, 6.73, 95% CI, 3.65-12.40) and leukemia (HR, 6.30; 95% CI, 3.75-10.58), had the greatest MDD risk versus matched controls. Patients who received inpatient chemotherapy as initial treatment had a higher risk for MDD than patients without chemotherapy (HR, 0.43; 95% CI, 0.30-0.62). CONCLUSIONS: Adolescent and young adult patients in Japan with cancer are at high risk for MDD. Particularly, those with multiple cancer categories, leukemia, and those who receive aggressive anticancer treatments should be monitored closely for symptoms of MDD.

Risk of major depressive disorder in Japanese cancer patients: A matched cohort study using employer-based health insurance claims data.

OBJECTIVE: Patients with cancer are at high risk of depression. However, the risk of major depressive disorder (MDD) after cancer diagnosis has not been studied in a population setting in Japan. This cohort study used a Japanese medical claims database to examine time to MDD in cancer patients and the risk of MDD (hazard ratio; HR) compared with matched cancer-free controls. METHODS: Primary endpoint was time to MDD (starting 6 months before cancer diagnosis) in adult (18-74 years) cancer patients; secondary endpoint was time to MDD (6 months before to 12 months after cancer diagnosis) in a matched cohort of cancer patients and cancer-free controls. Multivariate analyses were performed to determine HRs for all cancers and for each cancer site. RESULTS: Of 35 008 cancer patients (mean age, 53.3 years), 2201 (6.3%) were diagnosed with MDD within 66 months. Matched cancer patients (n = 30 372) had an elevated risk of MDD compared with cancer-free controls (n = 303 720; HR [95% confidence interval] 2.96 [2.77-3.16]). MDD risk was highest in patients with multiple cancers, pancreatic cancer, and brain cancer. Compared with middle-aged patients, risk was higher in patients <40 years old and lower in patients ≥65 years old; risk tended to be higher in women than in men. CONCLUSIONS: Compared with cancer-free individuals, Japanese patients with cancer, mostly <65 years old, had an almost threefold higher risk of developing MDD within 12 months of cancer diagnosis. Physicians should watch for MDD in cancer patients and treat when necessary.

Pre-emptive skin treatments to prevent skin toxicity caused by anti-EGFR antibody: the real-world evidence in Japan.

AIM: Clinically managing skin toxicity associated with anti-EGFR antibody usage to treat colorectal cancer improves quality of life for colorectal cancer patients. This study assesses trends of pre-emptive skin treatments and their impact on subsequent dermatologist visits in Japanese colorectal cancer patients. PATIENTS & METHODS: Pre-emptive treatment status and dermatologist visit data were investigated for 9461 colorectal cancer patients who experienced anti-EGFR antibody treatment. Data were collected from an electronic hospital-based claims database. RESULTS: Pre-emptive treatments increased around 2013. Furthermore, subsequent dermatologist visits decreased significantly among the pre-emptive treatment group (p < 0.05). CONCLUSION: Pre-emptive skin treatments seem to be related to reducing subsequent dermatologist visits by severe skin toxicity prevention and gained popularity in Japan.

Minimum Cost Estimation of a Baseline Survey for a Molecular Epidemiology Cohort Study: Collecting Participants in a Model Region in Japan.

BACKGROUND: Some recent molecular epidemiology studies of the effects of genetic and environmental factors on human health have required the enrollment of more than 100 000 participants and the involvement of regional study offices across the country. Although regional study office investigators play a critical role in these studies, including the acquisition of funds, this role is rarely discussed. METHODS: We first differentiated the functions of the regional and central study offices. We then investigated the minimum number of items required and approximate cost of a molecular epidemiology study enrolling 7400 participants from a model region with a population of 100 000 for a 4-year baseline survey using a standard protocol developed based on the protocol of Japan Public Health Center-based Prospective Study for the Next Generation. RESULTS: The functions of the regional study office were identified, and individual expenses were itemized. The total cost of the 4-year baseline survey was 153 million yen, excluding consumption tax. Accounting difficulties in conducting the survey were clarified. CONCLUSIONS: We investigated a standardized example of the tasks and total actual costs of a regional study office. Our approach is easy to utilize and will help improve the management of regional study offices in future molecular epidemiology studies.

Impact of Depression Onset and Treatment on the Trend of Annual Medical Costs in Japan: An Exploratory, Descriptive Analysis of Employer-Based Health Insurance Claims Data.

INTRODUCTION: We aimed to clarify medical expenses in Japanese individuals before and after major depressive disorder (MDD) diagnosis, and to determine whether MDD treatment also reduces medical costs for comorbid physical conditions. METHODS: This was an exploratory, descriptive, retrospective analysis of insurance claims data from JMDC Inc. Cohort A included individuals aged 18-64 years between January 2015 and December 2019. Cohorts B and C included Cohort A individuals with diabetes/hypertension ('chronic disease'), and sleep/anxiety disorders ('high depression risk'), respectively. Individuals in Cohorts A-C with an MDD diagnosis were analyzed by year of MDD onset (Cohorts A-CMDD2015-2019). Diagnoses and median medical costs were derived from International Classification of Diseases 10 codes. RESULTS: Total medical and non-neuropsychiatric drug costs in MDD onset years were 170,390-182,120 and 8480-9586 yen higher, respectively, for Cohorts AMDD2015-2019 than for Cohort A. In Cohort AMDD2019, total medical and non-neuropsychiatric drug costs increased incrementally from 2015 to 2019 (total changes: + 165,130 and + 7365 yen, respectively), to a greater degree than in Cohort A (+ 10,510 and + 1246 yen, respectively). Neuropsychiatric drug costs increased in the year of MDD onset only and decreased thereafter. After MDD onset, decreases in total medical and non-neuropsychiatric drug costs were observed (Cohorts AMDD2015-2019). Non-neuropsychiatric drug costs also decreased after MDD onset in the chronic disease groups (Cohorts CMDD2015-2019), but not in patients with MDD recurrence. CONCLUSION: Treating MDD reduces medical costs for comorbid physical conditions and may be a useful strategy for improving healthcare efficiency in Japan.

Diseases prevalent before major depressive disorder diagnosis: an exploratory nested case-control study using health insurance-based claims data.

OBJECTIVES: Major depressive disorder (MDD) is often comorbid with other chronic and/or serious diseases. However, little is known about the prevalence of various diseases that are present before MDD onset. We examined the prevalence of all pre-existing diseases in the 12 months before an MDD diagnosis. DESIGN: Exploratory nested case-control study. SETTING: Data, including diagnoses based on International Statistical Classification of Diseases and Related Health Problems, 10th revision codes, were from a Japanese health insurance database (JMDC). PARTICIPANTS: Adults newly diagnosed with MDD during 2015, 2016 or 2017 (but not the preceding year) (cases) were matched (exact) 1:10 to controls by age, sex, index date and working status. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of patients in each group with each pre-existing disease during the 12 months before the index date (ie, before MDD diagnosis in cases). Odds ratios (ORs) for onset of MDD were calculated for each pre-existing disease. A post hoc multivariate analysis examined interactions of metabolic risk factors (diabetes, hypertension, dyslipidaemia), psychiatric disorders (sleep disorders, psychiatric disorders other than depression) and MDD-related symptoms (headache, pain, autonomic nerve imbalance) on MDD diagnosis. RESULTS: There were 13 420 cases and 134 200 controls (mean age 41.9 years; 66.5% male). The prevalence of almost all pre-existing diseases was higher in cases than in controls. The highest ORs (5.8-21.0) were for psychiatric diseases and sleep disorders. Insomnia (21.1% of patients; OR 8.7) and neurosis (9.7%; OR 10.6) were particularly prevalent in the case group. The odds of MDD increased in the presence of metabolic risk factors, psychiatric disorders and/or MDD-related symptoms. CONCLUSIONS: There is a high prevalence of pre-existing diseases in Japanese patients who develop MDD compared with matched controls without MDD. These results suggest that patients with chronic and/or serious diseases should be actively monitored for depression.

Health-Related Quality of Life Over 6 Months in Patients With Major Depressive Disorder Who Started Antidepressant Monotherapy.

OBJECTIVES: Major depressive disorder (MDD) is increasing worldwide and is associated with impaired quality of life (QOL). This study aimed to assess the QOL and its association with cognitive symptoms in patients with MDD who started antidepressant monotherapy. METHODS: Data from the PERFORM (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder) study were analyzed. A descriptive epidemiological analysis on EQ-5D-5L utility score, the level of each dimension, and the EuroQoL visual analog scale value was conducted at 4 visits during 6 months' follow-up. The association between cognitive complaints and changes in QOL measures was analyzed using multivariate linear regression analysis. RESULTS: The median EQ-5D-5L utility score improved from 0.67 at baseline to 0.82 at month 6. Although the proportion of patients reporting level 1 (no problem) in every dimension of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression increased over time, less than half of the patients achieved level 1 in pain/discomfort and depression/anxiety, which were closely related to depression and usual activities at month 6. Patients with no cognitive complaints or no history of MDD at baseline showed greater improvement in EQ-5D-5L utility scores and EuroQoL visual analog scale value for measuring QOL than those with these characteristics. CONCLUSIONS: Treatment over 6 months improved QOL in patients with MDD although there remained room for improvement in dimensions of usual activities, pain/discomfort, and depression/anxiety. Cognitive complaints or history of MDD at baseline predicted less improvement in QOL at 6 months. Any history of MDD might delay improvement in QOL after treatment.

Prediction of residual cognitive disturbances by early response of depressive symptoms to antidepressant treatments in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) frequently retain cognitive disturbances after recovery from mood symptoms. We investigated the relationship between early response of mood symptoms and/or remission, and residual cognitive disturbances after 6 months of antidepressant treatment. METHODS: 518 patients with MDD were followed up for 6 months after antidepressant treatment initiation (first-line or switch from a previous drug). Subjective and objective cognitive disturbances were assessed by the Perceived Deficits Questionnaire - Depression (PDQ-D) and digit symbol substitution test (DSST), respectively. Depressive symptoms, as well as remission and early response to treatment, were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Multivariable linear and logistic regression models were used to adjust for confounders. RESULTS: Early response of depressive mood (≥50% reduction in MADRS score at month 1) was related with fewer residual subjective cognitive symptoms, as evaluated by the PDQ-D at month 6 (p<0.001). Likewise, early remission status at month 2 was inversely associated with PDQ-D scores at month 6 (p<0.001). Among patients with baseline DSST scores of ≥1 standard deviation below the norm, early response/remission was associated with better performance on the DSST at month 6 (p<0.05). LIMITATIONS: The cohort may not be representative of the general MDD patient population, and the possible influence of concomitant medications was not evaluated. CONCLUSIONS: These findings suggest that early improvements in depressive symptoms predict better cognitive outcomes in patients with MDD. Grouping of patients by mood and cognition status in early stages of antidepressant treatments may facilitate efforts to improve long-term functional outcomes.

Treatment of Major Depressive Disorder in Japanese Patients with Cancer: A Matched Cohort Study Using Employer-Based Health Insurance Claims Data.

BACKGROUND AND OBJECTIVE: Patients with cancer are at high risk of major depressive disorder (MDD), but little is known about their MDD treatment. We investigated the use of antidepressants and other drugs for MDD after cancer diagnosis, and patient characteristics associated with their use. METHODS: Adults with a new cancer diagnosis were matched to cancer-free patients using a Japanese employee health insurance database (JMDC); this exploratory analysis included only cohort patients diagnosed with MDD between 6 months before and 12 months after the cancer diagnosis index month. Initial prescription frequencies of antidepressants and other MDD medications were compared between cancer and cancer-free groups and analyzed according to age, sex, and hospital characteristics. RESULTS: Compared with the cancer-free group (n = 4097), significantly fewer patients in the cancer group (n = 1199) were prescribed antidepressants {622 (51.9%) [95% CI 49.0-54.7] vs 2385 (58.2%) [95% CI 56.7-59.7]}, particularly selective serotonin reuptake inhibitors. In contrast, prescription of other medications, especially antipsychotics and anxiolytics (tandospirone, hydroxyzine), was more frequent in the cancer group than in the cancer-free group. In the cancer group, women were prescribed antidepressants (mostly selective serotonin reuptake inhibitors) and other medications (mostly benzodiazepines) more than men. Antidepressant prescription decreased with age; patients aged < 40 years had the highest selective serotonin reuptake inhibitor and the lowest conventional antidepressant prescription rate compared with patients aged 40-64 years and ≥ 65 years. Lower selective serotonin reuptake inhibitor and benzodiazepine prescription rates were seen in large (≥ 100 beds) hospitals and in hospitals where patients received their cancer diagnosis. CONCLUSIONS: These results suggest Japanese patients with cancer may be undertreated for MDD compared with cancer-free patients. However, when prescribed, medications may be chosen according to patient needs, including avoiding adverse effects and drug-drug interactions.