Abstract
Introduction
Cancer diagnoses are associated with considerable psychological distress and increased incidence of new mental health disorders (MHDs). Our aim was to identify patterns and differences in the emergence of new MHDs within the first year following a cancer diagnosis, using data from a diverse, multi‐institutional cancer cohort including more than half a million patients within a statewide academic health system.
Methods
The University of California Data Discovery Platform was used, which aggregates data of all patients at University of California–affiliated hospitals. We identified a cohort consisting of all adult patients with a cancer diagnosis and no documented MHDs before cancer diagnosis between 2013 and 2023. Multivariable adjusted time‐partitioned hazard ratios for overall all‐cause mortality were constructed using epochs of 12 through 35, 36 through 59, and 60 through 120 months.
Results
A total of 371,897 patients (mean age, 62.1 years) did not have a diagnosis. Following an incident cancer diagnosis, 39,687 patients (10.6%) developed a new MHD within a year. Of these, 13,904 (35.0%) were newly prescribed one or more oral psychotropic medications. After adjusting for covariates, early MHD was found to be linked to increased all‐cause mortality in the initial 12 through 35 months (hazard ratio, 1.51; 95% CI, 1.47–1.56), which diminished over time, observed as 1.17 (95% CI, 1.11–1.24) for 36 through 59 months and 0.95 (95% CI, 0.89–1.01) for 60 through 120 months.
Conclusions
Patients with cancer who experience a mental health condition are at an increased risk of all‐cause mortality. This reinforces and emphasizes existing recommendations for prompt screening and management of distress and mental health following a cancer diagnosis.
Keywords: anxiety disorders, cancer, depression, mental health disorders, mortality
Short abstract
In a cohort of more than 371,000 patients, early MHD was associated with higher mortality in the first 12 through 35 months after diagnosis, but this risk decreased over time. The findings highlight the importance of early screening and intervention for mental health conditions following a cancer diagnosis to potentially reduce mortality risks.
INTRODUCTION
Patients with cancer frequently face psychological distress, with approximately one third experiencing mental health disorders (MHDs). 1 Psychological reactions and even the development of MHDs in the context of cancer are a key source of increased morbidity and mortality. The profound stress of receiving a cancer diagnosis significantly amplifies the difficulty of managing cancer. An excessively strong or prolonged psychological reaction to the diagnosis may result in additional severe health issues, including depression, anxiety, and, in severe instances, suicide following a cancer diagnosis. 2 , 3 In addition, in the past decade, growing evidence has highlighted the adverse effect that newly diagnosed MHDs, including mood, anxiety, and substance abuse disorders, can have on cancer management, outcomes and cancer‐related mortality. 4 , 5 Several studies found an association between MHDs and higher mortality rates, whether from all‐ or cancer‐specific causes. 6 , 7
Nonetheless, previous studies often have limited applicability because of small sample sizes and the reliance on unverified self‐reported symptoms rather than clinically documented mental health diagnoses. 8 , 9 Few large‐scale studies have focused on clinically verified mental disorders, especially those that develop after a cancer diagnosis, and their association with mortality. Moreover, the specific effects of newly identified mental health conditions and the role of psychotropic medication on patients with cancer’s survival have not been extensively explored.
In a previous study, 10 we identified an association between newly diagnosed MHDs after receiving a cancer diagnosis and early mortality at a single academic medical center. The objective of our current study was to identify patterns and differences in the emergence of new MHDs within the first year after a cancer diagnosis, using data from a diverse, multi‐institutional cancer cohort within a statewide academic health system. Furthermore, we sought to investigate the relationship between these newly identified MHDs and overall mortality rates.
METHODS
Study population
We identified a cohort of adult patients (aged 18 years and older) who were newly diagnosed with cancer at University of California–affiliated hospitals from January 2013 to January 2023. This study used the University of California Data Discovery Platform and University of California Health Data Warehouse, which compile anonymized electronic health records (EHRs) using the Observational Medical Outcome Partnership's common data model. Patients were eligible if they had a minimum of two encounters spaced at least 30 days apart. We identified new cancer cases based on diagnosis codes from both outpatient and inpatient records. The study was exempt from institutional review board approval because of exclusive use of deidentified data.
Clinical variables
Cancer diagnoses and MHD were identified using the International Classification of Diseases, 10th Revision, codes. Cancer types were categorized by anatomic site. We also collected other clinical data, including age at cancer diagnosis, sex, race, ethnicity, and the modified Charlson comorbidity score, 11 excluding malignancy. Data on psychotropic medication use for patients with MHDs, including the first prescription and total number of prescriptions, were gathered from electronic medical record medication orders by health care providers. The psychotropic medications studied included selective serotonin receptor inhibitors (SSRIs), tricyclic antidepressants, non‐SSRI antidepressants, antipsychotics, nonbenzodiazepine anxiolytics, benzodiazepines, and lithium.
Exposures and outcomes
All documented mental health disorders were identified throughout the medical record. Early MHDs after a first cancer diagnosis were considered the primary exposure, defined as psychotic (F20–29), mood (F30–39), or anxiety (F40–48) disorders newly identified within 12 months after cancer diagnosis. We also examined early MHD cases that required medication, defined as the initiation of a new psychotropic medication within 12 months of cancer diagnosis. The main outcome we investigated was all‐cause mortality. We determined the time to death calculating from the date the incident cancer diagnosis code first appeared, using the California Death Certificate Registry.
Statistical analysis
Descriptive statistics were used to describe the cohort and are presented in means and SDs or counts and percentages. To estimate median follow‐up time, we used the Kaplan–Meier method. To determine the association between MHDs and all‐cause and cancer‐specific mortality, we calculated multivariable adjusted mortality hazard ratios using time‐partitioned epochs of 12 through 35, 36 through 59, and 60 through 120 months. These were selected a priori to correspond to early, intermediate, and long‐term survivorship phases, respectively, and to account for potential nonproportional hazards over time. All models were adjusted for age, sex, race, the baseline modified Charlson comorbidity score, cancer site, and MHD diagnosis. The hazard ratios (HR) and odds ratios (OR) presented here are based on these multivariate adjusted models, unless specified differently. We conducted all statistical tests as two‐tailed, considering p ≤ .05 as statistically significant. All analyses were performed using Python 3.9 and R 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
Cohort characteristics
A total of 371,897 patients (mean age being 62.1 years [SD 14.2]) who did not have a diagnosis of MHD predating cancer diagnosis were included (see Table 1). A total of 49.6% of the patients were female; 61.6% were White, 10.2% Asian, 3.5% Black, and 12.0% Hispanic/Latino. The median follow‐up time after the first documented cancer diagnosis was 28.2 months (interquartile range, 9–66). Among these patients, 85,792 died during the study period (23.1%, 5‐year overall survival: 72%); the overall survival curves by cancer site are presented in Supplementary Figure 1.
TABLE 1.
Clinical and demographic characteristics of all patients and those with early MHDs.
| All patients (n = 371 897) | MHD (n = 39 687) | |
|---|---|---|
| Age, mean (SD) | 62.1 (14.2) | 59.2 (14.6) |
| Gender, n (%) | ||
| Female | 184 395 (49.6) | 23 664 (59.6) |
| Male | 187 409 (50.4) | 16 021 (40.4) |
| Race, n (%) | ||
| American Indian or Alaska Native | 1310 (0.4) | 186 (0.5) |
| Asian | 38 084 (10.2) | 3086 (7.8) |
| Black or African American | 13 005 (3.5) | 1583 (4.0) |
| Multiracial | 6794 (1.8) | 920 (2.3) |
| Native Hawaiian | 1727 (0.5) | 154 (0.4) |
| White | 229 149 (61.6) | 25 988 (65.5) |
| Unknown | 37 373 (10.0) | 2414 (6.1) |
| Other race | 44 455 (12.0) | 5356 (13.5) |
| Ethnicity, n (%) | ||
| Hispanic or Latino | 44 766 (12.0) | 6061 (15.3) |
| Not Hispanic or Latino | 293 021 (78.8) | 31 716 (79.9) |
| Unknown | 34 110 (9.2) | 1910 (4.8) |
| Modified Charlson Score, n (%) | ||
| 0 | 281 277 (75.6) | 27 966 (70.5) |
| 1 | 25 587 (6.9) | 3131 (7.9) |
| 2 | 15 382 (4.1) | 1884 (4.7) |
| 3 | 5516 (1.5) | 717 (1.8) |
| 4 | 4434 (1.2) | 564 (1.4) |
| 5+ | 39 701 (10.7) | 5425 (13.7) |
| Cancer subtype, n (%) | ||
| Bladder and ureter | 9403 (2.5) | 1033 (2.6) |
| Bone soft tissue and sarcoma | 10 949 (2.9) | 1443 (3.6) |
| Breast | 53 628 (14.4) | 6577 (16.6) |
| Central nervous system | 12 675 (3.4) | 1782 (4.5) |
| Colorectal | 19 177 (5.2) | 2408 (6.1) |
| Gastrointestinal, other | 6688 (1.8) | 922 (2.3) |
| Gynecologic | 20 298 (5.5) | 2697 (6.8) |
| Head and neck | 12 647 (3.4) | 1851 (4.7) |
| Hematologic | 41 954 (11.3) | 5260 (13.3) |
| Kidney and renal pelvis | 8039 (2.2) | 760 (1.9) |
| Liver and bile duct | 11 869 (3.2) | 1476 (3.7) |
| Lung | 14 711 (4.0) | 1776 (4.5) |
| Melanoma | 18 448 (5.0) | 1361 (3.4) |
| Metastatic | 13 319 (3.6) | 1663 (4.2) |
| Other | 30 206 (8.1) | 3157 (8.0) |
| Pancreatic | 7678 (2.1) | 1161 (2.9) |
| Prostate | 44 195 (11.9) | 2319 (5.8) |
| Skin other | 36013 (9.7) | 2041 (5.1) |
Abbreviation: MHDs, mental health disorders.
Prevalence of cancer sites, mental health diagnoses, and psychotropic medications
The most prevalent sites of cancer were breast (14.4%), prostate (11.9%), and hematologic (11.3%). Following an incident cancer diagnosis, 39,687 patients (10.6%) developed a new MHD within a year. Of these, 13,904 (35.0%) were newly prescribed one or more oral psychotropic medications. The most frequently diagnosed early MHDs were generalized anxiety disorder (43.0%, Table 2), major depressive disorder (35.5%), and reactive/adjustment disorder (10.5%). After diagnosis, 24.6% of patients with cancer were prescribed an oral benzodiazepine, 9.4% received a non‐SSRI antidepressant, and 8.9% were prescribed an SSRI (Table 3). The specific indications for or impact of these prescriptions was not available in this dataset.
TABLE 2.
Types of new‐onset early MHDs.
| MHD patients (n = 39 687) | |
|---|---|
| Bipolar disorder | 664 (1.7%) |
| Depressive disorders | 14 107 (35.5%) |
| Manic disorder | 21 (0.1%) |
| Reactive and adjustment disorder | 4172 (10.5%) |
| Psychotic disorder | 1211 (3.1%) |
| Generalized anxiety | 17 080 (43.0%) |
| Other neurotic stress or anxiety disorder | 1269 (3.2%) |
| Other | 1163 (2.9%) |
Note: If a patient had multiple documented MHDs, the first diagnosis chronologically recorded was included in this table.
Abbreviation: MHD, mental health disorders.
TABLE 3.
Types of new‐onset psychotropic medications.
| All patients with cancer (n = 371 897) | |
|---|---|
| Antipsychotic | 12 829 (3.4%) |
| Nonbenzodiazepine anxiolytic | 1794 (0.4%) |
| Benzodiazepine | 91 440 (24.6%) |
| Lithium | 241 (0.1%) |
| Non‐SSRI antidepressant | 35 066 (9.4%) |
| SSRI | 32 905 (8.9%) |
| Tricyclic antidepressant | 7539 (2.0%) |
Abbreviation: SSRI, selective serotonin reuptake inhibitor.
Timing of onset of mental health diagnoses, and psychotropic medications after a cancer diagnosis
In patients who received an early MHD diagnosis, the most frequently observed cancers were breast cancer (16.6%) and hematologic cancers (13.3%). The likelihood of a new MHD diagnosis increased starting from three months before a cancer diagnosis, reaching a significant peak in the first six months following the diagnosis, as illustrated in Figure 1. This increase showed an early peak shortly after the cancer diagnosis. Cancers with lower survival rates were found to be more strongly associated with the likelihood of a new MHD diagnosis when compared to prostate cancer, which was used as a baseline. For instance, pancreatic cancer had an OR of 3.2 (95% CI, 2.98–3.46), in contrast to nonmelanoma skin cancers with an OR of 1.1 (95% CI, 1.0–1.2).
FIGURE 1.
Timeline of mental health diagnoses (MHDs) among patients with cancer. This figure displays the distribution of MHD diagnoses in relation to the timing of cancer diagnoses across various cancer types. Each graph shows MHD incidence over time, with day 0 (marked by a red dashed line) representing the date of cancer diagnosis. Peaks in MHD diagnoses around day 0 indicate a high incidence of new mental health conditions shortly after cancer diagnosis across most cancer types. The figure illustrates that new MHDs diagnosis began to increase approximately three months before cancer diagnosis and peaked during the first six months afterward. This prediagnosis rise is shown for context but was not included in the analytic definition of early MHD.
Mortality over time associated with new‐onset mental health diagnoses
Because of the highest increase in the probability of MHD occurring within the first 12 months after a cancer diagnosis, and to minimize the impact of immortal time bias, the study then focused on the effects of a new, early MHDs during this period, with or without new psychotropic medication, on all‐cause mortality. This was analyzed using multivariable models that adjusted for covariates as detailed in the Methods section. After adjusting for covariates, early MHDs were found to be linked to increased all‐cause mortality in the initial 12 through 35 months (HR, 1.51; 95% CI, 1.47–1.56), which diminished over time, observed as 1.17 (95% CI, 1.11–1.24) for 36 through 59 months and 0.95 (95% CI, 0.89–1.01) for 60 through 120 months, as shown in table 4. Similar trends were noted for early MHDs with psychotropic medications, where it was associated with higher all‐cause mortality in the first 12 through 35 months (HR, 2.67; 95% CI, 2.52–2.83), which decreased to 1.25 (95% CI, 1.07–1.46) in 36 through 59 months and stabilized to 1.01 (95% CI, 0.82–1.25) in 60 through 120 months (Supplementary Figure 2).
TABLE 4.
Time‐stratified hazard ratios for MHD exposures.
| 12–36 months | 36–60 months | 60–120 months | |
|---|---|---|---|
| Early MHD | 1.51 (1.47–1.56) a | 1.17 (1.11–1.24) a | 0.95 (0.89–1.01) |
| Early MHD + PM | 2.67 (2.52–2.83) a | 1.25 (1.07–1.46) a | 1.01 (0.82–1.25) |
Note: Models adjusted for age, sex, race, and the baseline modified Charlson comorbidity score and cancer site.
Abbreviations: MHD, mental health disorder; PM, psychotropic medications.
p < .01.
DISCUSSION
In a large multi‐institutional cohort, our study found that, after an incident cancer diagnosis, 10.6% of patients developed an early MHD, and most within 6 months of cancer diagnosis. Among these individuals, 35.0% were prescribed one or more oral psychotropic medications. The likelihood of receiving a new MHD diagnosis and the initiation of new psychotropic medication treatment increased starting from three months before a cancer diagnosis and peaking within the first six months after diagnosis. Furthermore, diagnosis of an early MHD was associated with an increased all‐cause mortality in the initial 12 through 35 months. This association diminished over time, highlighting the temporal dynamics between mental health issues and mortality following a cancer diagnosis.
The likelihood of early MHDs varied across different sites of cancer, with a more pronounced association seen in patients with cancers characterized by lower survival rates. Specifically, individuals with pancreatic cancer, which has a 5‐year overall survival rate of ∼11%, 12 exhibited a significantly higher probability of an early MHD diagnosis, with an OR of 3.2. This contrasted with the marginally higher risk of early MHDs observed in cancers with a more favorable prognosis, such as prostate cancer when adjusted for age, sex, race, and the baseline modified Charlson comorbidity score. This underscores the critical need for mental health screening and psychological support, particularly for cancers with poor prognoses, as the presence of MHDs can negatively impact survival outcomes, through mechanisms still under investigation, affecting both the progression of the disease and the response to treatment. 13
The observed increase in incidence of new MHDs in this study, beginning just before and then spiking immediately following a cancer diagnosis, could indicate the onset of cancer‐related symptoms at a population level, consistent with previously noted increases in sickness absence prior to a cancer diagnosis. 14 Moreover, this rise in risk may be attributed to both psychological factors, such as distress and uncertainty surrounding the diagnostic process, and biological mechanisms, including systemic inflammation, hypothalamic‐pituitary‐adrenal axis dysregulation, and adverse effects of medications used during cancer workup and initial treatment. 15 A notable limitation of our research is the reliance on diagnostic codes within EHR, where the observed surge in MHDs might be influenced by documentation bias. Nevertheless, by integrating data on both clinical diagnoses and medication prescriptions, we aimed to capture the full spectrum of mental health burden faced during the period surrounding a cancer diagnosis. This approach allowed for a more nuanced evaluation of the relationship between early MHDs and patient survival.
In our cohort, 10.6% of patients developed a new MHD within 12 months of cancer diagnosis, which is modestly higher than the 8.2% incidence reported in a large single‐institution U.S. EHR study by Chen et al., and comparable to the 11 457 cases (4.7%) reported by Zhu et al. in a Swedish nationwide registry when restricting to mood‐, anxiety‐, and substance‐related disorders. 5 , 10 Among patients with early MHDs in our analysis, 35% received a psychotropic prescription, which is lower than the 53% reported by Chen et al., yet higher than the 20.9% of patients with cancer who regularly used psychotropic medication in the first 180 days reported by Wang et al. using the Taiwanese National Health Insurance database. 10 , 15 These cross‐study differences likely reflect variations in health care systems, thresholds for psychiatric referral, and definitions of regular medication use. Importantly, our cohort was demographically and culturally diverse, with 38.4% identifying as non‐White and 12.0% as Hispanic/Latino (greater diversity than reported in comparable registry or institutional cohorts), which supports the generalizability of our findings and underscores the need to ensure equitable screening and treatment of cancer‐related mental health conditions across populations.
Our observation that all‐cause mortality is higher in the short term for patients diagnosed with an early MHD and who received a prescription for psychotropic medication aligns with findings from previous research, 7 , 9 , 16 including a previous study conducted by our team. 10 The higher HRs observed among patients with early MHDs who received psychotropic medications may reflect a more severe or clinically significant mental health burden, as pharmacologic treatment is often initiated for moderate to severe symptomatology. These patients may also experience overlapping behavioral and biological vulnerabilities, including reduced treatment adherence, social withdrawal, or medication side effects, which could contribute to poorer survival outcomes. Alternatively, the observed association could be partly influenced by indication, whereby patients with more advanced disease or higher symptom burden are more likely to be prescribed psychotropic medications.
In our cohort, benzodiazepines were prescribed more frequently than other classes of psychotropic medications, even though SSRIs are generally recommended as first‐line therapy for anxiety and depressive disorders. This pattern could be concerning, as benzodiazepine use has been linked to higher mortality risk and potential adverse interactions, particularly in medically complex patients with cancer. These findings emphasize the importance of early identification and management of mental health disorders, as well as appropriate referral for psychiatric or behavioral health consultation to ensure evidence‐based psychotropic medication management.
Our study has limitations. The data used do not have accurate information on severity of MHDs, the stage of cancer, or treatment modalities received. Our dataset does not include information about the indications for the prescription of psychotropic medications identified. The precise reason for the prescription of these medications is not known but could include non–mental health indications (e.g., the use of an SNRI for pain management, rather than to treat depression or anxiety). Furthermore, although prior research has suggested that some MHD subtypes may have a particularly stronger association with mortality, our sample size limited our ability to perform robust stratified analyses by MHD subtype. Additionally, we do not have detailed cause of death data. To mitigate this, we adjusted for the site of cancer, recognizing the substantial differences in overall prognosis between cancer sites, such as pancreas versus prostate cancer. The incidence of early MHDs identified in this study likely represents an underestimation of the actual prevalence of psychological distress and mental health issues among patients with cancer when compared with estimates derived from interviews and direct assessments. However, the recording of an MHD in EHR may offer a closer reflection of how psychological distress and mental health symptoms are recognized or treated in the context of real‐world cancer care.
CONCLUSION
Patients with cancer who experience a mental health condition and are prescribed psychotropic medication after their diagnosis are at an increased risk of all‐cause mortality. Our study's generalizability is noteworthy, as it involves one of the largest cohorts by examining patients from University of California–affiliated hospitals that serve populations with diverse demographics. These findings reinforce and emphasize existing recommendations for prompt screening and management of distress and mental health following a cancer diagnosis.
AUTHOR CONTRIBUTIONS
Amir Ashraf Ganjouei: Conceptualization; investigation; writing—original draft; methodology; validation; visualization; writing—review and editing; software; formal analysis; project administration; data curation; supervision; resources. Travis Zack: Conceptualization; methodology; writing—review and editing; data curation; resources; writing—original draft. Isabel Friesner: Writing—original draft; writing—review and editing; software; resources; conceptualization. William C. Chen: Conceptualization; writing—original draft; writing—review & editing; formal analysis; resources. Lauren Boreta: Conceptualization; writing—original draft; writing—review & editing; methodology; resources. Steve E. Braunstein: Conceptualization; writing—original draft; writing—review and editing; validation; resources. Michael W. Rabow: Conceptualization; writing—original draft; writing—review & editing; resources; project administration. Maria E. Garcia: Conceptualization; writing—original draft; writing—review and editing; project administration; resources. Julian C. Hong: Conceptualization; investigation; funding acquisition; writing—original draft; writing—review and editing; visualization; validation; methodology; software; formal analysis; resources; supervision; data curation; project administration.
CONFLICT OF INTEREST STATEMENT
None.
Supporting information
Supplementary Material
Supplementary Material
Supplementary Material
ACKNOWLEDGMENTS
The authors thank the Center for Data‐Driven Insights and Innovation (CDI2) at the University of California Health (UCH) for its analytical and technical support related to the use of the UC Health Data Warehouse (UCHDW) and related data assets, including the UC COVID Research Data Set (CORDS).
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
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Supplementary Materials
Supplementary Material
Supplementary Material
Supplementary Material
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.