Cumulative burden of psychiatric disorders and self-harm across 26 adult cancers

Abstract

Cancer is a life-altering event causing considerable psychological distress. However, information on the total burden of psychiatric disorders across all common adult cancers and therapy exposures has remained scarce. Here, we estimated the risk of self-harm after incident psychiatric disorder diagnosis in patients with cancer and the risk of unnatural deaths after self-harm in 459,542 individuals. Depression was the most common psychiatric disorder in patients with cancer. Patients who received chemotherapy, radiotherapy and surgery had the highest cumulative burden of psychiatric disorders. Patients treated with alkylating agent chemotherapeutics had the highest burden of psychiatric disorders, whereas those treated with kinase inhibitors had the lowest burden. All mental illnesses were associated with an increased risk of subsequent self-harm, where the highest risk was observed within 12 months of the mental illness diagnosis. Patients who harmed themselves were 6.8 times more likely to die of unnatural causes of death compared with controls within 12 months of self-harm (hazard ratio (HR), 6.8; 95% confidence interval (CI), 4.3-10.7). The risk of unnatural death after 12 months was markedly lower (HR, 2.0; 95% CI, 1.5-2.7). We provide an extensive knowledge base to help inform collaborative cancer-psychiatric care initiatives by prioritizing patients who are most at risk.

Fig. 1. Cumulative burden of psychiatric disorders in patients with cancer.

a–c, Distribution of cumulative burden by 26 cancer diagnostic groups (a), 10 cancer treatment modalities (b) and 11 chemotherapy drug classes (c). All data and 95% CIs are provided in the supplementary tables.

Fig. 1. Cumulative burden of psychiatric disorders in patients with cancer.

a–c, Distribution of cumulative burden by 26 cancer diagnostic groups (a), 10 cancer treatment modalities (b) and 11 chemotherapy drug classes (c). All data and 95% CIs are provided in the supplementary tables.

Fig. 2. Temporal variation in the first diagnosis of psychiatric disorder in relation to the time of the first occurrence of self-harm.

a, By cancer type. b, By age group. c, By index of multiple deprivation (IMD) status. d, By the number of prevalent noncancer comorbidities. Bars on the left side of the graphs indicate the proportion of individuals who were diagnosed with a psychiatric disorder before the first self-harm event. Bars on the right side of the graphs indicate the proportion of individuals who were diagnosed with a psychiatric disorder after the first self-harm event. Prevalence ratios (prevalence of psychiatric disorder diagnosis before self-harm divided by prevalence of psychiatric disorder after self-harm) are shown, alongside 95% CIs.

Fig. 3. Total burden and risk of self-harm after diagnosis of psychiatric disorders in patients with cancer.

Case (with psychiatric disorder) and control (no psychiatric disorder) groups were obtained via propensity score matching (Extended Data Fig. 1). Controls were matched by age at cancer diagnosis, cancer type, sex, IMD and primary care practice ID. a, Cumulative burden of all self-harm events in cases and controls. b, Cumulative incidence of the first self-harm event in cases and controls. Gray’s test was used to assess statistical significance. c, HRs for risk of self-harm for each psychiatric disorder were further adjusted for noncancer comorbidities, cancer treatment and presence of other psychiatric disorders. The numbers of patients with psychiatric disorder were as follows: depression, 21,609; anxiety disorder, 20,070; schizophrenia, 7,679; bipolar disorder, 557; personality disorder, 194; substance abuse, 115,868. The numbers of matched controls for each psychiatric disorder were as follows: depression, 75,087; anxiety disorder, 67,887; schizophrenia, 23,130; bipolar disorder, 1,636; personality disorder, 628; and substance abuse, 126,057. Self-harm risks during the first 12 months and subsequent years of follow-up are shown. Strata with low event numbers (n < 10) were not analyzed. Data are presented as HRs, and error bars represent 95% CIs. Numbers in the graphs in panel c represent P values. The likelihood ratio test was used. Full data and 95% CIs are provided in the supplementary tables.

Fig. 4. Cumulative incidence of all-cause mortality and YLL after diagnosis of psychiatric disorders in patients with cancer.

Case (with psychiatric disorder) and control (no psychiatric disorder) groups were obtained via propensity score matching (Extended Data Fig. 1). Controls were matched by age at cancer diagnosis, cancer type, sex, IMD and primary care practice ID. a, Cumulative incidence curves for all-cause mortality after psychiatric disorder diagnosis in matched case and control groups. The log-rank test was used. b, Excess YLL attributable to psychiatric disorders in patients with cancer. Radar plots depict the difference in YLL between matched cases and controls. Excess YLL was estimated based on the age of onset of a psychiatric disorder. All data and 95% CIs are provided in Supplementary Table S7.

Fig. 5. Risk of suicide and other causes of death following self-harm in patients with cancer.

Case (self-harm) and control (no self-harm) groups were obtained via propensity score matching (Extended Data Fig. 2). Controls were matched by age at cancer diagnosis, cancer type, sex, IMD and primary care practice ID. a, HRs for risk of suicide and other causes of death were further adjusted for noncancer comorbidities, cancer treatment and presence of psychiatric disorders. Mortality risks during the first 12 months and subsequent years of follow-up are shown. We identified 5,683 individuals with incident self-harm and 18,407 matched controls. Data are presented as HRs, and error bars represent 95% CIs. The likelihood ratio test was used. Numbers in the graphs represent P values. b, Cumulative incidence curves of death due to all causes, natural causes and unnatural causes after self-harm in matched case and control groups. Gray’s test was used. *The results for natural deaths are adjusted for competing risk of unnatural deaths. The results for unnatural deaths are adjusted for competing risk of natural deaths.

Extended Data Fig. 1. Flow diagram of case and control identification via propensity score matching for analyses on risk of self-harm after the diagnosis of psychiatric disorders in patients with cancer.

Psychiatric disorders diagnostic groups are as follow: (a) depression, (b) anxiety disorders, (c) schizophrenia, schizotypal and delusional disorders, (d) bipolar affective disorder and mania (e) personality disorders and (f) substance abuse. Patients can be included in more than one diagnostic group for cases. Controls were matched by age at cancer diagnosis, cancer type, sex, Index of Multiple Deprivation and primary care practice ID.

Extended Data Fig. 2. Flow diagram of case and control identification via propensity score matching for analysis on the risk of suicide and other causes of death following self-harm in patients with cancer.

Controls were matched by age at cancer diagnosis, cancer type, sex, Index of Multiple Deprivation and primary care practice ID.