Depression is a comorbid, disabling syndrome that affects up to approximately 25% of cancer patients.[1-3] This prevalence significantly exceeds the prevalence in the general population.[4] However, most patients do not receive potentially effective treatments, and only 5% see a mental health professional.[2]

In contrast to depression in the general population, depression in people with cancer is believed to affect men and women equally.[5] Individuals and families who face a diagnosis of cancer experience varying levels of stress and emotional upset. Depression in patients with cancer not only affects the patients themselves, but also has a major negative impact on their families.

Definitions: Depression is suspected when a number of specific symptoms such as low affect, sleep disturbance, and distorted thought patterns are observed. These are specified in the categorization of psychiatric/behavioral disorders in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition.[6]

Normally, a patient’s initial emotional response to a diagnosis of cancer is brief, extending over several days to weeks, and may include feelings of disbelief, denial, or despair. This normal response is part of a spectrum of depressive symptoms that range from normal sadness to adjustment disorder with depressed mood to major depression.[6] Other syndromes described include the following:

  • Dysthymia: a chronic mood disorder in which a depressed mood is present on more days than not for at least 2 years.
  • Subsyndromal depression (also called minor depression or subclinical depression): an acute mood disorder that is less severe (some, but not all, diagnostic symptoms present) than major depression.

Possible Causes of Depressive Symptoms in People With Cancer

  • Experience of loss or anticipated loss.
  • Uncontrolled pain.[7][Level of evidence: II]
  • Metabolic abnormalities:
    • Hypercalcemia.
    • Sodium/potassium imbalance.
    • Anemia.
    • Vitamin B12 or folate deficiency.
    • Fever.
  • Primary or metastatic central nervous system tumors.
  • Disruption of sleep due to medical treatments.
  • Endocrine abnormalities:
    • Hyperthyroidism or hypothyroidism.
    • Adrenal insufficiency.
  • Medications:[8];[9][Level of evidence: II];[10]
    • Steroids.
    • Endogenous and exogenous cytokines, i.e., interferon-alfa and aldesleukin (interleukin-2 [IL-2]).[11]
    • Methyldopa.
    • Reserpine.
    • Barbiturates.
    • Propranolol.
    • Some antibiotics (e.g., amphotericin B).
    • Some chemotherapeutic agents (e.g., procarbazine, asparaginase).
    • Hormone therapy (e.g., androgen deprivation therapy).[12][Level of evidence: III]

A survey in England of women with breast cancer showed that among several factors, depression was the strongest predictor of emotional and behavioral problems in their children.[13] Fear of death, disruption of life plans, changes in body image and self-esteem, changes in social role and lifestyle, and financial and legal concerns are significant issues in the life of any person with cancer, yet not everyone who is diagnosed with cancer experiences serious depression or anxiety. However, many patients with cancer can experience moderately severe depression and anxiety. For example, in a study of 256 women who underwent chemotherapy treatment for early breast cancer, 26% and 41% of study participants reported moderately severe depression and anxiety, respectively. This treatment phase warrants close monitoring of patients’ psychological well-being.[14]

The use of hormone therapy or second-generation antiandrogen therapy is also associated with increased risk of depression. In a retrospective study of 210,804 patients with prostate cancer identified from the Surveillance, Epidemiology, and End Results–Medicare (SEER-Medicare) and Texas Cancer Registry–Medicare linked databases, 3% of patients received second-generation antiandrogen therapy.[12][Level of evidence: III] Using a multivariable Cox proportional hazards model, patients who received second-generation antiandrogen therapy had a greater increased risk of depression, compared with a no-hormone-therapy group (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.79–2.59; P < .001) and with a traditional-hormone-therapy group (HR, 2.26; 95% CI, 1.88–2.73; P < .001).[12][Level of evidence: III] While this secondary analysis was a limitation of this study, the large sample size merits consideration for monitoring for depression in patients undergoing hormone therapy, particularly second-generation antiandrogen therapy.

In a study of 149 women with nonmetastatic breast cancer, 40% reported at least mild depression at the end of chemotherapy.[15] Up to 5.6 years postchemotherapy, 23% had received a new psychiatric diagnosis, 62% were prescribed a psychotropic medication, and 21% engaged in mental health specialty care.

Just as patients require ongoing evaluation for depression and anxiety throughout their course of treatment, so do family caregivers. In a study of family caregivers of patients in the palliative phase of illness, both male and female caregivers experienced significantly more anxiety than did a sample of noncaregivers, while there was an increased incidence of Hospital Anxiety and Depression Scale–defined depression among women.[16]

Some people may have more difficulty adjusting to the diagnosis of cancer than others do and will vary in their responses to the diagnosis. Sadness and grief are normal reactions to the crises faced during cancer. All people will experience these reactions periodically. Because sadness is common, it is important to distinguish between normal degrees of sadness and depressive disorders. An end-of-life care consensus panel review article describes details regarding this important distinction and illustrates the major points using case vignettes.[17] A critical part of cancer care is the recognition of the levels of depression present and determination of the appropriate level of intervention, ranging from brief counseling or support groups to medication and/or psychotherapy. For example, relaxation and counseling interventions have been shown to reduce psychological symptoms in women with a new diagnosis of gynecological cancer.[18]

Major depression, which is more common in cancer patients than in the general population,[3] has recognizable symptoms whose diagnosis and treatment are essential because they have an impact on quality of life.[19] Major depression may also impact survival. In a large study of 20,582 patients treated for breast, colorectal, gynecological, and prostate cancers across Scotland, United Kingdom, across all cancer diagnoses, having major depression was associated with worse survival (pooled HR, 1.41; 95% CI, 1.29–1.54; P < .001).[20][Level of evidence: II] Similarly, in a population-based study of 13,244 individuals with diffuse large B-cell lymphoma identified through the SEER-Medicare database,[21][Level of evidence: III] compared with patients with no mental health disorders, those with depression had the highest 5-year mortality rate (HR, 1.37; 95% CI, 1.28–1.47), followed by those with co-occurring depression and anxiety (HR, 1.23; 95% CI, 1.08–1.41) and those with anxiety alone (HR, 1.17; 95% CI, 1.06–1.29).

Further, disparities in cancer care have been identified among individuals who have preexisting major depression and/or other severe mental illnesses. A large systematic review and meta-analysis (N = 299,193) [22][Level of evidence: III] found that individuals with breast cancer with preexisting major depression, schizophrenia, and/or bipolar disorder received delayed and discordant care, compared with individuals with cancer without these disorders. Given the high prevalence of depression among patients with cancer, this health care disparity warrants attention.

Depression is also an underdiagnosed disorder in the general population. Symptoms evident at the time of a cancer diagnosis may represent a preexisting condition and warrant separate evaluation and treatment.

Depression and anxiety disorders are common among patients receiving palliative care and contribute to a greatly diminished quality of life in these patients.[23] In the Canadian National Palliative Care Survey, patients receiving palliative care for cancer (N = 381) were evaluated for depressive and anxiety disorders and for the impact of these disorders on quality of life. The primary assessment tool was a modified version of the Primary Care Evaluation of Mental Disorders. A significant number of participants (24.4%; 95% CI, 20.2%–29.0%) were found to fulfill diagnostic criteria for at least one depressive or anxiety disorder (20.7% prevalence for depressive disorder and 13.1% for anxiety disorder).

Participants diagnosed with a depressive or anxiety disorder had the following characteristics:

  • Were significantly younger than the other participants (P = .002).
  • Had lower performance status (P = .017).
  • Had smaller social networks (P = .008).
  • Participated less in organized religious services (P = .007).

They also reported more severe distress about physical symptoms, social concerns, and existential issues, suggesting significant negative impact on other aspects of their quality of life.[23]

The importance of psychological issues was underscored by another study conducted in terminally ill cancer patients (n = 211) with life expectancies of less than 6 months.[24] Investigators evaluated patient “sense of burden to others” and its correlation with physical, psychological, and existential issues, using specific validated psychometrics (e.g., visual analog scale). The variables most highly correlated with sense of burden to others included:

  • Depression (r = 0.460, P < .0001).
  • Hopelessness (r = 0.420, P < .0001).
  • Outlook (r = 0.362, P < .0001).

In multiple regression analysis, four variables predicted perception of burden to others:

  • Depression.
  • Hopelessness.
  • Level of fatigue.
  • Current quality of life.

No association between sense of burden to others and actual degree of physical dependency was found, implying that this perception is mainly mediated through psychological distress and existential issues. A subanalysis of patient groups from different settings suggested that these findings were consistent across the inpatient and outpatient settings, with some minor variations.[24]

The emotional response to a diagnosis of cancer (or cancer relapse) may begin as a dysphoric period marked by increasing turmoil. The individual will experience sleep and appetite disturbance, anxiety, ruminative thoughts, and fears about the future. Epidemiological studies, however, suggest that at least one-half of all people diagnosed with cancer will successfully adapt.

Strategies to promote psychological adjustment to a diagnosis of cancer and other chronic diseases include the following:[25]

  • Remaining as active and engaged in life as possible.
  • Expressing emotions in a way that helps to achieve insight.
  • Self-management (including healthy diet and exercise).
  • Focusing on potential positive outcomes of illness.

Some studies suggest an association between maladaptive coping styles and higher levels of depression, anxiety, and fatigue symptoms.[26,27] Examples of maladaptive coping behaviors include the following:

  • Avoidant or negative coping.
  • Negative self-coping statements.
  • Preoccupation with physical symptoms.
  • Catastrophizing.

One study conducted in a group of 86 mostly late-stage cancer patients suggested that maladaptive coping styles and higher levels of depressive symptoms are potential predictors of the timing of disease progression.[27] Another study examining coping strategies in women with breast cancer (n = 138) concluded that patients with better coping skills such as positive self-statements have lower levels of depressive and anxiety symptoms.[26] The same study found racial differences in the use of coping strategies, with African American women reporting and benefiting more from the use of religious coping strategies such as prayer and hopefulness than did White women.[26]

Preliminary data suggest a beneficial impact of spirituality on associated depression, as measured by the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being questionnaire and the Hamilton Depression Rating Scale.[28]

The following indicators may suggest a need for early intervention:

  • A history of depression.
  • A weak social support system (not married, few friends, a solitary work environment).
  • Evidence of persistent irrational beliefs or negativistic thinking regarding the diagnosis.
  • A more serious prognosis.
  • Greater dysfunction related to cancer.

As shown by a study of adult cancer patients (n = 48) and their adult relatives (n = 99), family functioning is an important factor that impacts patient and family distress. Families that were able to act openly, express feelings directly, and solve problems effectively had lower levels of depression, and direct communication of information within the family was associated with lower levels of anxiety.[29] Depressive symptoms in spouses of patients with cancer can also have a negative impact on their marital communication. A preliminary study investigated 19 potential predictors of depression in spouses (n = 206) of women with nonmetastatic breast cancer.[30] Spouses were more likely to experience depressive symptoms if they:

  • Were older.
  • Were less well-educated.
  • Were more-recently married.
  • Reported heightened fears about their spouse’s well-being.
  • Worried about their job performance.
  • Were more uncertain about their future.
  • Were in marriages that were less well-adjusted.

Risk factors may be different, especially pain and other physical symptoms.[31] When the clinician begins to suspect that a patient is depressed, he or she will assess the patient for symptoms. Mild or subclinical levels of depression that include some, but not all, of the diagnostic criteria for a major depressive episode can cause considerable distress and may warrant interventions such as supportive individual or group counseling, either by a mental health professional or through participation in a self-help support group.[32]

Evidence-based recommendations have described various approaches to the problems of cancer-related fatigue, anorexia, depression, and dyspnea.[33] Even in the absence of any symptoms, many patients express interest in supportive counseling; clinicians can accommodate these patients with referrals to qualified mental health professionals. However, when symptoms are more intense, longer lasting, or recurrent after apparent resolution, treatment to alleviate symptoms is essential.[19,34,35] Anxiety and depression in early treatment are good predictors of these same problems at 6 months.[36] In a study of older women with breast cancer, a recent diagnosis of depression was associated with both a greater likelihood of not receiving definitive cancer treatment and poorer survival.[37]

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

References
  1. Krebber AM, Buffart LM, Kleijn G, et al.: Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments. Psychooncology 23 (2): 121-30, 2014. [PUBMED Abstract]
  2. Walker J, Hansen CH, Martin P, et al.: Prevalence, associations, and adequacy of treatment of major depression in patients with cancer: a cross-sectional analysis of routinely collected clinical data. Lancet Psychiatry 1 (5): 343-50, 2014. [PUBMED Abstract]
  3. Mitchell AJ, Chan M, Bhatti H, et al.: Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol 12 (2): 160-74, 2011. [PUBMED Abstract]
  4. Pitman A, Suleman S, Hyde N, et al.: Depression and anxiety in patients with cancer. BMJ 361: k1415, 2018. [PUBMED Abstract]
  5. Miller S, Lo C, Gagliese L, et al.: Patterns of depression in cancer patients: an indirect test of gender-specific vulnerabilities to depression. Soc Psychiatry Psychiatr Epidemiol 46 (8): 767-74, 2011. [PUBMED Abstract]
  6. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Association, 2013.
  7. Ciaramella A, Poli P: Assessment of depression among cancer patients: the role of pain, cancer type and treatment. Psychooncology 10 (2): 156-65, 2001 Mar-Apr. [PUBMED Abstract]
  8. Drugs that cause psychiatric symptoms. Med Lett Drugs Ther 31 (808): 113-8, 1989. [PUBMED Abstract]
  9. Capuron L, Ravaud A, Neveu PJ, et al.: Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 7 (5): 468-73, 2002. [PUBMED Abstract]
  10. Rogers D, Pies R: General medical with depression drugs associated. Psychiatry (Edgmont) 5 (12): 28-41, 2008. [PUBMED Abstract]
  11. Menzies H, Chochinov HM, Breitbart W: Cytokines, cancer and depression: connecting the dots. J Support Oncol 3 (1): 55-7, 2005 Jan-Feb. [PUBMED Abstract]
  12. Nowakowska MK, Lei X, Wehner MR, et al.: Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer. JAMA Netw Open 4 (12): e2140803, 2021. [PUBMED Abstract]
  13. Watson M, St James-Roberts I, Ashley S, et al.: Factors associated with emotional and behavioural problems among school age children of breast cancer patients. Br J Cancer 94 (1): 43-50, 2006. [PUBMED Abstract]
  14. Nakamura ZM, Deal AM, Nyrop KA, et al.: Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer. Oncologist 26 (2): 147-156, 2021. [PUBMED Abstract]
  15. Nakamura ZM, Damone EM, Herrick HP, et al.: Anticipating mental health needs after chemotherapy in early-stage breast cancer using patient-reported symptom screening. Support Care Cancer 30 (5): 3933-3941, 2022. [PUBMED Abstract]
  16. Grov EK, Dahl AA, Moum T, et al.: Anxiety, depression, and quality of life in caregivers of patients with cancer in late palliative phase. Ann Oncol 16 (7): 1185-91, 2005. [PUBMED Abstract]
  17. Block SD: Assessing and managing depression in the terminally ill patient. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians - American Society of Internal Medicine. Ann Intern Med 132 (3): 209-18, 2000. [PUBMED Abstract]
  18. Petersen RW, Quinlivan JA: Preventing anxiety and depression in gynaecological cancer: a randomised controlled trial. BJOG 109 (4): 386-94, 2002. [PUBMED Abstract]
  19. Lynch ME: The assessment and prevalence of affective disorders in advanced cancer. J Palliat Care 11 (1): 10-8, 1995 Spring. [PUBMED Abstract]
  20. Walker J, Mulick A, Magill N, et al.: Major Depression and Survival in People With Cancer. Psychosom Med 83 (5): 410-416, 2021. [PUBMED Abstract]
  21. Kuczmarski TM, Tramontano AC, Mozessohn L, et al.: Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: a population-based study. Lancet Haematol 10 (7): e530-e538, 2023. [PUBMED Abstract]
  22. Kisely S, Alotiby MKN, Protani MM, et al.: Breast cancer treatment disparities in patients with severe mental illness: A systematic review and meta-analysis. Psychooncology 32 (5): 651-662, 2023. [PUBMED Abstract]
  23. Wilson KG, Chochinov HM, Skirko MG, et al.: Depression and anxiety disorders in palliative cancer care. J Pain Symptom Manage 33 (2): 118-29, 2007. [PUBMED Abstract]
  24. Chochinov HM, Kristjanson LJ, Hack TF, et al.: Burden to others and the terminally ill. J Pain Symptom Manage 34 (5): 463-71, 2007. [PUBMED Abstract]
  25. de Ridder D, Geenen R, Kuijer R, et al.: Psychological adjustment to chronic disease. Lancet 372 (9634): 246-55, 2008. [PUBMED Abstract]
  26. Reddick BK, Nanda JP, Campbell L, et al.: Examining the influence of coping with pain on depression, anxiety, and fatigue among women with breast cancer. J Psychosoc Oncol 23 (2-3): 137-57, 2005. [PUBMED Abstract]
  27. Beresford TP, Alfers J, Mangum L, et al.: Cancer survival probability as a function of ego defense (adaptive) mechanisms versus depressive symptoms. Psychosomatics 47 (3): 247-53, 2006 May-Jun. [PUBMED Abstract]
  28. Nelson CJ, Rosenfeld B, Breitbart W, et al.: Spirituality, religion, and depression in the terminally ill. Psychosomatics 43 (3): 213-20, 2002 May-Jun. [PUBMED Abstract]
  29. Edwards B, Clarke V: The psychological impact of a cancer diagnosis on families: the influence of family functioning and patients' illness characteristics on depression and anxiety. Psychooncology 13 (8): 562-76, 2004. [PUBMED Abstract]
  30. Lewis FM, Fletcher KA, Cochrane BB, et al.: Predictors of depressed mood in spouses of women with breast cancer. J Clin Oncol 26 (8): 1289-95, 2008. [PUBMED Abstract]
  31. Patrick DL, Ferketich SL, Frame PS, et al.: National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002. J Natl Cancer Inst 95 (15): 1110-7, 2003. [PUBMED Abstract]
  32. Meyer TJ, Mark MM: Effects of psychosocial interventions with adult cancer patients: a meta-analysis of randomized experiments. Health Psychol 14 (2): 101-8, 1995. [PUBMED Abstract]
  33. Dy SM, Lorenz KA, Naeim A, et al.: Evidence-based recommendations for cancer fatigue, anorexia, depression, and dyspnea. J Clin Oncol 26 (23): 3886-95, 2008. [PUBMED Abstract]
  34. Massie MJ, Holland JC: Overview of normal reactions and prevalence of psychiatric disorders. In: Holland JC, Rowland JH, eds.: Handbook of Psychooncology: Psychological Care of the Patient With Cancer. Oxford University Press, 1989, pp 273-82.
  35. Massie MJ, Shakin EJ: Management of depression and anxiety in cancer patients. In: Breitbart W, Holland JC, eds.: Psychiatric Aspects of Symptom Management in Cancer Patients. American Psychiatric Press, 1993, pp 470-91.
  36. Nordin K, Glimelius B: Predicting delayed anxiety and depression in patients with gastrointestinal cancer. Br J Cancer 79 (3-4): 525-9, 1999. [PUBMED Abstract]
  37. Goodwin JS, Zhang DD, Ostir GV: Effect of depression on diagnosis, treatment, and survival of older women with breast cancer. J Am Geriatr Soc 52 (1): 106-11, 2004. [PUBMED Abstract]