Incidence and temporal trends of depression and anxiety following cancer diagnosis in Japan: Insights from the LIFE study.

Abbreviations

anatomical therapeutic chemical

International Statistical Classification of Diseases, 10th Revision

incidence rate ratios

longevity improvement and fair evidence

BACKGROUND

Depression and anxiety are frequent complications of cancer. 1 Cancer patients who develop depression have shown lower adherence to cancer treatment and poorer survival outcomes, 2 , 3 , 4 , 5 and are at a higher risk of suicide. 6 Similarly, anxiety has been reported to negatively affect treatment adherence and quality of life in cancer patients. 1 , 7

The prevalence of depression and anxiety in cancer patients has been widely reported, with estimates of approximately 20% and 10%, respectively. 1 In contrast, the incidence of these disorders is less documented. Research suggests that the risk of developing mental disorders is highest within the first 12 months after cancer diagnosis. 1 , 8 , 9 In particular, the period immediately following diagnosis has been reported as having the highest overall risk for mental disorders. At present, the detailed temporal trends in depression and anxiety, as well as their associations with treatment‐related factors, remain unclear. The prevalence of depression and anxiety in the general population varies by country, 10 but there is scarce information on their occurrence among cancer patients in Japan. Identifying the incidence of these mental disorders and elucidating the time points with the highest risk of occurrence could help to determine the optimal timing for interventions to support the mental health of newly diagnosed cancer patients.

This study aimed to clarify the incidence and temporal trends of depression and anxiety following cancer diagnosis in Japan.

MATERIALS AND METHODS

Study design

This study was designed as a cohort study with a primary focus on descriptive epidemiology. An overview of the study design is presented in Figure S1 . The primary outcomes were depression incidence and anxiety incidence within 2 years after cancer diagnosis in newly diagnosed cancer patients. The secondary outcomes included (i) temporal trends in depression and anxiety incidence, and (ii) incidence and trends stratified by sex, age, cancer type, and treatment modality. The enrolment period for study participants was from fiscal year 2018 to 2020 (fiscal years in Japan run from April until March of the following year). The follow‐up period was set as 24 months after cohort entry or until the last available claims record, whichever came first. This duration of 24 months was determined based on previous studies indicating that the first year after cancer diagnosis is a high‐risk period for developing mental disorders, 1 , 8 , 9 as well as with consideration to the cancer treatment period and data collection time frame.

Study setting

All data used in this study were retrospectively extracted from the Longevity Improvement and Fair Evidence (LIFE) Study database, which contains data from approximately 30 municipalities. The LIFE Study is a longitudinal database project led by Kyushu University (Fukuoka, Japan) that collects various health and welfare‐related data from participating municipalities, with a focus on inpatient and outpatient medical claims data. 11 These data, which are integrated at the individual level using unique anonymized identifiers, are collected from persons enrolled in either of Japan's public medical insurance systems: National Health Insurance (which covers the self‐employed, irregularly employed, unemployed, and those working in primary industries aged ≤74 years) and the Latter‐Stage Older Persons Health Care System (which covers individuals aged ≥75 years). Municipal governments serve as insurers under these systems. Further details about the LIFE Study have been reported elsewhere. 12 For this study, we focused on 14 municipalities that had data available during the study period from April 2017 to March 2023 (corresponding to fiscal years 2017 to 2022).

Study cohort

The study cohort comprised patients who received one or more diagnoses of cancer during the enrolment period. Cancer diagnoses were identified using International Statistical Classification of Diseases, 10th Revision (ICD‐10) codes D00‐D09 and C00‐C97. The cancer types and their corresponding ICD‐10 codes are listed in Table S1 . In individuals with multiple cancer codes, the earliest registered code with the smallest numerical value was selected. Each patient's month of cancer diagnosis was set as his/her cohort entry month.

Several exclusion criteria were applied. First, patients aged <15 years were excluded, as we sought to focus on non‐paediatric cancer cases. Second, patients in which the first medical claims record appeared within 12 months before their cohort entry month were excluded to ensure a sufficient look‐back period. Third, patients previously diagnosed with cancer within 12 months before their cohort entry month were excluded, based on a previous study that used a similar look‐back period. 13 Fourth, patients previously diagnosed with depression or anxiety within 12 months before their cohort entry month were excluded. Fifth, patients without any cancer treatment within the first 12 months after their cohort entry month were excluded to increase the specificity of cancer patient identification. Lastly, patients with diagnoses of carcinoma in situ were excluded, as the small number of such cases could complicate the interpretation of the results. Ultimately, patients with newly diagnosed cancer, as defined by the above criteria, were included in the analysis.

Outcomes

The study outcomes were depression incidence and anxiety incidence during the 2‐year follow‐up period. Depression was defined using the ICD‐10 codes F32 and F33. Anxiety was defined using the ICD‐10 code F41, excluding specific phobia subtypes.

Covariates

The sex of each subject was determined based on the information recorded in the database at the time of entry, meaning that we adopted the legally designated sex under Japanese law. Age was analyzed as a categorical variable because the study database provided age in 5‐year intervals instead of exact values as part of the anonymization process. For this study, we categorized patients into those aged 15–64 years and ≥65 years. Cancer treatment was categorized into the following three modalities: surgical treatment (e.g., surgical and endoscopic resection, radiofrequency ablation, and laser ablation), radiotherapy, and chemotherapy. Surgical treatment was identified using K codes assigned to surgical procedures in the Japanese insurance claims system (Table S2 ). Radiotherapy was defined based on the presence of certain M codes, which are radiotherapy‐related codes in the Japanese insurance claims system. Chemotherapy was identified using Japanese drug codes and the corresponding Anatomical Therapeutic Chemical (ATC) Classification System codes (Table S3 ).

Statistical analysis

First, the crude incidence rates of depression and anxiety were calculated as the number of events divided by the total person‐months at risk; these rates were expressed per 1000 person‐months. In addition to calculating the overall incidence rates, we also calculated the incidence rates for subgroups defined by sex, age group (15–64 or ≥65 years), use or non‐use of each treatment modality, and cancer type. The same analysis was also performed for different combinations of treatment modalities. Furthermore, to examine the associations between mental disorder incidence and various patient and treatment factors, Poisson regression was used to estimate the adjusted incidence rate ratios (IRRs) according to sex, age, and treatment modality. As information on surgical treatment and radiotherapy was only available for solid tumours, all related analyses were limited to patients with solid cancers.

Next, we estimated the temporal changes in the incidence rates of depression and anxiety using a previously described method. 14 Incidence rates were estimated by aggregating monthly patient and event counts, applying Poisson regression with the number of patients as an offset, and converting the estimated events into rates per 1000 person‐months. A natural spline function (degrees = 3, degrees of freedom = 7) was used for smoothing. Cumulative risk was calculated as 1 − exp.(−cumulative rate) for the follow‐up period. The same analyses were repeated after stratification by sex, age, and treatment modality. For the cancer type–specific analysis, we focused on the following major cancers with high incidence and mortality rates in Japan: breast, colorectal, liver, lung, pancreatic, prostate, and stomach cancer. 15 Additionally, cancers with particularly high risks for depression and anxiety were analysed separately. These were defined as cancers with a crude depression or anxiety incidence rate of ≥5 per 1000 person‐months, a sample size of ≥300 cases, and ≥50 events.

To examine the potential relationships between cancer‐related examinations and the temporal trends in outcomes, we calculated the numbers of patients who underwent examinations per month. Using the D codes and E codes from the Japanese insurance claims system, we identified the following examinations: ultrasonography (D215), plain radiography (E001, E002), computed tomography (E200), magnetic resonance imaging (E202), and nuclear medicine, which included scintigraphy (E100) and positron emission tomography (E101).

Furthermore, since previous studies have reported that the incidence of depression and anxiety can increase even before a cancer diagnosis, 8 , 9 the incidence rates and their temporal trends were also evaluated from 2 months before diagnosis (study design overview presented in Figure S2 ). With the entry point set at −2 months, the look‐back period for depression and anxiety was redefined as −12 to −3 months before the cancer diagnosis month.

All data processing and statistical analyses were performed using R version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

Patient characteristics

A total of 22,863 newly diagnosed cancer patients were included in the analysis (Figure 1 ), and their characteristics are summarized in Table 1 . Female patients accounted for 45.2% of the study cohort. The majority of patients (96.3%) were aged ≥65 years, with a particularly high proportion aged 70–79 years. During the 2‐year follow‐up period, depression was diagnosed in 1,520 patients (6.6%), and anxiety was diagnosed in 1,402 patients (6.1%). Surgical treatment was performed in 75.5% of patients, radiotherapy in 20.1%, and chemotherapy in 38.5%. Stomach cancer was the most prevalent cancer type (20.9%), followed by lung cancer (11.3%), prostate cancer (10.1%), breast cancer (9.1%), and colorectal cancer (7.8%).

Crude incidence rates of depression and anxiety

The crude incidence rates of depression are shown in Table S4 , with an overall rate of 3.36 per 1000 person‐months. The incidence rate was higher in female patients than in male patients, but was similar between patients aged 15–64 years and ≥65 years. Patients who underwent chemotherapy had higher depression incidence rates than those who underwent other treatments, and the highest rate was observed in those who received a combination of chemotherapy and radiotherapy (Figure S3 ). Among the cancer types, pancreatic cancer had the highest depression incidence rate, followed by brain/central nervous system tumours and other malignant neoplasms (Figure 2 A and Table S5 ).

The overall crude incidence rate of anxiety was 3.11 per 1000 person‐months (Table S4 ). The sex‐based trend was similar to that of depression. However, the anxiety incidence rate was notably higher in patients aged 15–64 years compared to those aged ≥65 years, with a greater difference than that observed for depression. Patients who underwent chemotherapy had higher anxiety incidence rates than those who underwent other treatments, and the highest rate was observed in those who received a combination of chemotherapy, radiotherapy, and surgical treatment (Figure S3 ). Among the cancer types, pancreatic cancer had the highest anxiety incidence rate, followed by oesophageal cancer and gallbladder/biliary tract cancer (Figure 2B and Table S6 ). Among all cancers, prostate cancer had the lowest incidence rates for both depression and anxiety.

Adjusted incidence rate ratios according to patient and treatment factors

Table S7 shows the adjusted IRRs of depression and anxiety during the two‐year follow‐up period. We observed significantly higher IRRs for both disorders in female patients (vs. male patients) and patients who received radiotherapy or chemotherapy (vs. those who did not receive these therapies). Additionally, older patients aged ≥65 years had a significantly lower IRR for anxiety than younger patients aged 15–64 years.

Temporal trends in incidence rates according to patient and treatment factors

The dynamic changes in depression incidence rates are illustrated in Figure 3 . The incidence of depression increased immediately after cancer diagnosis, peaked around the second month, and subsequently declined from the 3rd month (Figure 3A–L ). However, a smaller peak was observed around the 10th month after diagnosis. Between the age groups, patients aged 15 to 64 years had higher incidence rates during the month of diagnosis and the following month compared to patients aged ≥65 years (Figure 3E,F ). Next, patients who did not undergo surgical treatment had higher and more fluctuating incidence rates than those who underwent surgery (Figure 3G,H ). Patients who received chemotherapy consistently had a higher incidence rate than those who did not throughout the entire follow‐up period (Figure 3I,J ). In contrast, the incidence rates were higher in patients who received radiotherapy than those who did not until approximately 10 months after diagnosis, after which no major differences were observed (Figure 3K,L ).

For anxiety, unlike depression, the highest incidence rate was observed in the month of cancer diagnosis, followed by a sharp decline thereafter (Figure 4A–L ). Female patients had a notably higher incidence rate than male patients, especially in the early period after diagnosis (Figure 4C,D ). While the age‐related difference in incidence rates was more pronounced for anxiety than depression during the early post‐diagnosis period, no clear differences were observed thereafter (Figure 4E,F ). Patients who did not undergo surgical treatment tended to have higher incidence rates, although the differences were not as large as those observed for depression (Figure 4G,H ). The trends for radiotherapy and chemotherapy were generally similar to those observed for depression (Figure 4I–L ). Overall, the fluctuations in incidence rates of anxiety were smoother than those of depression.

Temporal trends in incidence rates according to cancer type

The temporal trends in incidence rates of depression and anxiety were observed to vary among the cancer types (Figure 5 ). For depression, pancreatic cancer patients generally had the highest incidence rates, followed by liver and lung cancer patients (Figure 5A ). A common peak in incidence was observed around 10 to 11 months after diagnosis. Although not classified as major cancers in our study, oesophageal cancer and lip, oral cavity, and pharyngeal cancer showed high incidence rates comparable to those of pancreatic cancer.

For anxiety, pancreatic cancer patients generally had the highest incidence rates, but breast cancer patients had the highest incidence rates during the first 3 months following cancer diagnosis (Figure 5B ). Among the non‐major cancers, oesophageal cancer exhibited incidence trends similar to pancreatic cancer.

Potential influence of cancer‐related examinations

Because fluctuations were observed in depression incidence over time, we conducted an analysis to examine whether these variations could be influenced by cancer‐related examinations (Figure S4 ). The analysis showed increases in the number of patients undergoing examinations approximately 1 year after diagnosis (Figure S4A–E ). This trend was particularly pronounced for computed tomography (which is frequently used for whole‐body screening in cancer treatment) (Figure S4C ) and nuclear medicine examinations (which are relatively specific to cancer) (Figure S4E ).

Incidence rates and temporal trends beginning from the pre‐diagnosis period

In the analysis that included the 2 months before cancer diagnosis, the temporal trends in the incidence rates of depression (Figure S5A–L ) and anxiety (Figure S6A–L ) after diagnosis were similar to those observed in the main analysis. Although the increase in incidence rates before cancer diagnosis was modest, anxiety showed a slightly steeper increase when compared to depression.

DISCUSSION

This cohort study clarified the incidence rates and temporal trends of depression and anxiety among newly diagnosed cancer patients in Japan. Depression incidence peaked within the first 3 months after cancer diagnosis, whereas the highest incidence for anxiety was observed in the month of diagnosis. The temporal patterns of incidence varied depending on patient factors, treatment factors, and cancer types. Pancreatic cancer patients consistently exhibited the highest incidence rates for both disorders.

Approximately one in two Japanese individuals will be diagnosed with cancer during their lifetime, and the overall 5‐year survival rate is estimated to be 64%. 15 Accordingly, cancer is a disease that many people must learn to coexist with. Although cancer patients commonly experience depression and anxiety, 1 , 16 , 17 , 18 , 19 , 20 mental health issues are often overlooked in cancer treatment despite evidence of their negative impact on treatment adherence, quality of life, and survival. 1 , 2 , 3 , 4 , 5 , 7 There is little in the existing literature on the prevalence of depression and anxiety among Japanese cancer patients. 13 However, the prevalence of these mental disorders in the general Japanese population is reportedly lower than in Western countries, which may suggest ethnic or cultural differences. 10 , 21 , 22 In our search of the literature, we found only one study that examined the incidence of mental disorders before and after cancer diagnosis. 8 Understanding when these mental disorders are most likely to occur could facilitate the timely and efficient implementation of preventive measures.

There are two primary mechanisms through which depression and anxiety can occur in cancer patients. The first involves the interplay of biological, psychological, and social factors in what is described as the biopsychosocial model; and the second involves the neuropsychiatric effects induced by specific cancers and their treatments. 1 Although the risk factors for depression and anxiety in cancer patients have not been comprehensively identified, 1 younger age and female sex have been established as potential risk factors. 13 , 23 Furthermore, age‐ and sex‐related differences have been reported to be particularly pronounced in the period immediately following diagnosis. 8 In the present study, we observed differences in the incidence of both target outcomes according to age and sex during the first few months after diagnosis. These variations are likely attributable to the biopsychosocial model.

On the other hand, differences in incidence rates according to treatment modality are likely to be influenced by both the biopsychosocial model and the neuropsychiatric effects of cancers and their treatments. Certain treatments, such as chemotherapy including corticosteroid therapy, have been reported to be associated with depression, 1 suggesting that the treatments themselves may have contributed to the higher incidence rates of depression and anxiety in patients who underwent chemotherapy or radiotherapy. At the same time, treatment modality may also reflect cancer severity and its associated psychological distress, which could be explained by the biopsychosocial model. In our study, the incidence of depression was lower in the surgical treatment group, which may be attributable to the lower proportion of advanced cancer cases with limited curative treatment options.

Differences in incidence rates by cancer type can also be explained by both mechanisms. Certain cancers may release biochemicals that contribute to the development of depression, such as severe cytokine‐mediated depression in pancreatic cancer and endocrine paraneoplastic syndromes in lung cancer. 1 Similarly, thyroid dysfunction caused by thyroid cancer has been linked to depression. 24 In addition, cancers with poor prognoses (e.g., pancreatic cancer, lung cancer, brain tumours, and haematologic malignancies) have been reported to have higher risks of depression and anxiety, whereas cancers with relatively favourable prognoses (e.g., prostate and skin cancer) have lower risks of these disorders. 8 , 13 , 17 Furthermore, our study revealed that anxiety incidence was particularly high in breast cancer patients immediately after diagnosis. We posit that this could be attributed to the impact on female identity. Additionally, the consistently high incidence rates of depression and anxiety throughout the follow‐up period in oesophageal cancer and lip, oral cavity, and pharyngeal cancer may be due to the psychological stress associated with visible disfigurement of the face and neck region. These findings align with the biopsychosocial model.

Our observations that the incidence rates of depression and anxiety peaked shortly after cancer diagnosis support previous findings that suicide rates are elevated during the early post‐diagnosis period. 25 , 26 , 27 , 28 , 29 On the other hand, the increase in the incidence of mental disorders just before cancer diagnosis is believed to result from the psychological distress associated with the cancer diagnostic workup. 1 , 29 , 30 , 31 This study also identified a small peak in depression incidence around the 10th month after diagnosis. Given that the number of examinations increased approximately 12 months after diagnosis, it is possible that the anticipation of follow‐up evaluations contributed to this peak. This suggests that the same psychological processes experienced at the time of cancer diagnosis may play a role at this later stage.

The only study in the published literature that has clarified the temporal patterns of depression and anxiety among cancer patients is a cohort study conducted in Sweden. 8 While that study focused on the trends in hazard ratios compared to non‐cancer patients, our present study aimed to characterize the trends in direct incidence. Additionally, our study examined the potential influence of cancer treatments on mental health outcomes. Both these studies showed generally consistent trends with higher incidence rates of depression and anxiety among female patients, younger patients, and patients with poor‐prognosis cancers, as well as a rapid decline in incidence following diagnosis. However, our higher‐resolution monthly analysis newly revealed that the peak incidence of depression was not immediate, but instead occurred approximately 2 months after diagnosis. It has been well documented that anxiety often precedes depression. 32 Anxiety is an immediate response to unknown threats, whereas depression can develop later due to organic factors such as hormonal imbalance, chronic inflammation, and changes in neurotransmitters triggered by cancer and its treatment. These factors could explain why depression tends to manifest after some time following a cancer diagnosis.

This study has several limitations. First, no validation studies on the accuracy of depression and anxiety diagnoses in claims data have been conducted in Japan. However, the diagnostic threshold of mental disorders in Japan may be higher than in many other countries, 21 suggesting that the specificity of these diagnoses may be relatively high. Second, the accuracy of cancer diagnosis remains uncertain. Previous studies using Japanese claims data have defined cancer based solely on ICD‐10 codes. 13 However, we identified and excluded a substantial proportion of patients who received no cancer treatments after being diagnosed, which could indicate a potentially high rate of false positives with this approach. To improve the specificity of identification, we incorporated treatment history in our definition of cancer patients. We consider that relatively few patients would choose to forgo treatment after diagnosis, and that these patients are likely to have unique characteristics that preclude standard treatment. Thus, our incorporation of cancer treatments in the exclusion criteria likely produced a study cohort comprising more typical cancer patients undergoing standard care. Third, this study could not fully account for disease recurrence. Specifically, our cohort may include some patients who experienced a recurrence of cancer or mental disorder after an interval exceeding 12 months, which could introduce survival bias. Fourth, due to the nature of the database, the proportion of younger patients was relatively small. However, the results of this study were consistent with previous findings, thereby mitigating concerns about this limitation. Fifth, the dataset did not contain information on cancer characteristics such as stage or grade. Therefore, we could not fully disentangle the psychological impact of being diagnosed with a potentially severe cancer from the effects of treatment modalities such as chemotherapy or radiotherapy. Finally, the limited number of cases and events made it difficult to conduct detailed analyses of certain cancer subtypes. Nonetheless, our study covered the major cancer types and offers valuable insights for most healthcare providers and cancer patients.

CONCLUSION

This study clarified the incidence rates and temporal trends of depression and anxiety among newly diagnosed cancer patients in Japan, providing important insights into the appropriate timing for mental health interventions. By characterizing the epidemiological dynamics of these mental disorders according to age, sex, cancer type, and treatment modality, we identified at‐risk groups who may benefit from targeted interventions. These findings are expected to contribute to the enhancement of mental health support in cancer care, promotion of personalized medicine, and improvement of clinical practice guidelines. Future efforts should focus on establishing more effective support strategies and further advancing the field of psycho‐oncology.

AUTHOR CONTRIBUTIONS

Kengo Kawaguchi: Conceptualization; data curation; formal analysis; investigation; methodology; visualization; writing – original draft. Megumi Maeda: Data curation; resources; writing – review and editing. Fumiko Murata: Data curation; resources; writing – review and editing. Makoto Endo: Writing – review and editing. Yasuharu Nakashima: Writing – review and editing; supervision. Haruhisa Fukuda: Conceptualization; funding acquisition; supervision; writing – review and editing.

FUNDING INFORMATION

This study was supported by a grant from the Japan Science and Technology Agency's FOREST programme (Grant number: JPMJFR205J).

CONFLICT OF INTEREST STATEMENT

The authors have no relevant financial or non‐financial interests to disclose.

ETHICS STATEMENT

This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Kyushu University (Approval number 22114‐09). This study adopted an opt‐out approach for participant enrollment, and individual informed consent was not obtained.

Supporting information

DATA S1. Supporting information.

Kawaguchi K, Maeda M, Murata F, Endo M, Nakashima Y, Fukuda H. Incidence and temporal trends of depression and anxiety following cancer diagnosis in Japan: Insights from the LIFE study. Int J Cancer. 2026;158(3):621‐632. doi: 10.1002/ijc.70118

DATA AVAILABILITY STATEMENT

All source code is publicly available on GitHub ( https://github.com/Kawaken-KU/Psycho-Oncology_LIFE_Study ). Further information is available from the corresponding author upon request.

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Associated Data

Supplementary Materials

DATA S1. Supporting information.

Data Availability Statement

All source code is publicly available on GitHub ( https://github.com/Kawaken-KU/Psycho-Oncology_LIFE_Study ). Further information is available from the corresponding author upon request.