Depressive spectrum disorders in cancer: prevalence, risk factors and screening for depression: a critical review

Figures & data

Table 1. Main reviews/meta-analysis relative to depressive spectrum disorders in cancer.

Authors	Type of study	Sample	Results
Mitchell et al. [72]	Meta-analysis	56 diagnostic validity studies 10 009 patients	Case finding: 1 stem question, 2 stem questions and the BDI-II = Level 2 evidence (2a, 2b and 2c respectively) (grade B recommendation). Screening: 2 stem questions Level 1b evidence; BDI-II Level 2c evidence
Mitchell et al. [44]	Review and meta-analysis	43 studies 51 381 cancer survivors 217 630 healthy controls	Prevalence of depression 11.6% in cancer and 10.2% in healthy controls
Mitchell et al. [25]		24 studies, 4007 patients in palliative caresettings 70 studies, 10 071 patients in oncological/hematological settings	DSM = 16.5%; ICD = 14.3% major depression 9·6% minor depression; 15.4% adjustment disorder All types of depression = 24.6%; all types of mood disorder = 29%). DSM or ICD 16.3% 14.9% major depression; 19.2% minor depression; 19.4% adjustment disorder; 2.7% dysthymia All types of depression 20.7%; depression or adjustment disorder = 31.6%; any mood disorder = 38.2%
Walker et al. [17]	Review	66 relevant studies, only 15 (23%) met quality criteria	Prevalence of depression: 5–16% in outpatients; 4–14% in inpatients; 4–11% in mixed out/inpatient; 7–49% in palliative care. Expert interviewers (psychiatrists or clinical psychologists)=lower prevalence estimates
Krebber et al. [16]	Meta-analysis	211 studies (during or after treatment)	HADS-depression subscale (HADS-D) ≥ 8, HADS-D ≥11, Center for Epidemiologic Studies ≥16, and (semi-)structured diagnostic interviews were used to define depression in 66, 53, 35 and 49 studies, respectively. Respective mean prevalence of depression was 17% (95% CI 16–19%), 8% (95% CI 7–9%), 24% (95% CI 21–26%), and 13% (95% CI 11–15%) (p < 0.001). Prevalence of depression ranged from 3% in patients with lung cancer to 31% in patients with cancer of the digestive tract, on the basis of diagnostic interviews. Prevalence of depression was highest during treatment 14% (95% CI 11–17%), measured by diagnostic interviews, and 27% (95% CI 25–30%), measured by self-report instruments. In the first year after diagnosis, prevalence of depression measured with diagnostic interviews and self-report instruments were 9% (95% CI 7–11%) and 21% (95% CI 19–24%), respectively, and they were 8% (95% CI 5–12%) and 15% (95% CI 13–17%) ≥ 1 year after diagnosis
Robinson et al. [27]	Review	25 studies (33 articles); 4545 patients	Demoralization is prevalent in patients with progressive disease or cancer and clinically significant in 13–18%
Hotopf et al. [12]	Review	46 eligible studies on prevalence of depression; 4 studies on case finding	HADS: 29% median prevalence of 'definite depression' (score on the depression subscale >10) Psychiatric interviews: MDD = 5–26% (median 15%)
Mitchell et al. [94]	Meta-analysis	50 analyses testing HADS- depression subscale	In the identification of depression the HADS-T, HADS-D and HADS-A had a pooled sensitivity and specificity of 82.0%, 77.0%; 71.6%, 82.6% and 80.5%, 77.8%, respectively. All versions performed poorly in case finding but well in a screening capacity
Yang et al. [24]	Review and meta-analysis	17 eligible studies; 3497 Chinese adults with cancer	Depression = 54.90% in cancer patents vs. 17.50% in healthy subjects (OR = 7.85, 95% CI 5.56–11.07)

DSM: Diagnostic and Statistical Manual of Mental Disorders; HADS: Hospital Anxiety and Depression Scale; ICD: International Classification of Diseases; MDD: Major Depressive Disorder.

Table 3. Common assessment methods for depressive spectrum disorders in cancer settings.

Tools	Characteristics	Clinical use	Notes
Interviews
Structured Clinical Interview forDSM - SCID	Clinician Version and Standardresearch version to be used in research and clinical settings	Designed to be administered by aclinician or trained mental health professional	Assessment of current psychiatric patients, lifetime psychiatricdiagnoses in medical patients, family members, community samples
World Health Organization World Mental Health Composite International Diagnostic Interview (WHO WMH-CIDI)	Comprehensive, fully structured interview	Designed to be used by trained lay interviewers	Assessment of mental disorders according to the definitions and criteria of ICD-10 and DSM-IV in epidemiological and cross-cultural studies and for clinical and research purposes
Diagnostic Criteria for Psychosomatic Research (DCPR)	Clinical interview	Set of 12 psychosocial syndromes demoralization, disease phobia, health anxiety thanatophobia, illness denial, persistent somatization,functional somatic symptomssecondary to a psychiatric disorder, conversion symptoms, anniversary reaction, irritable mood, type A behavior, and alexithymia	Research evidence accumulated inseveral clinical settings (cardiology, oncology, gastroenterology, endocrinology, primary care, consultation psychiatry, nutrition, and community)
Short psychometric questionnaires
Hospital Anxiety Depression scale (HADS)	14 items (7 for anxiety;7 for depression) plus total score	Score HADS-D: 0–7 = normal; 8–10 = borderline case; 11–21 = case; HADS Total ≥15 Adjustment Disorders; ≥19 MDD	In oncology best thresholds for screening =15 for the HADS total (sensitivity 0.87; specificity 0.88), =7 for the HADS-D subscale (sensitivity 0.86; specificity 0.81 disorders [96]). Caution in any case in using thresholds [97] and in use for screening rather than case finding
Center for Epidemiologic Studies Depression Scale (CESD)	20 items 0–3 Likert scale	Scores ≥16: risk for clinical depression; ≥22: clinically relevant depression; ≥25: MDD	CESD-R (Revised version) also available, reflecting DSM5 diagnosis of MDD [98]
Beck depression Inventory II (BDI-II)	21 questions, each answerbeing scored on a scalevalue of 0–3	Score 14–19: mild depression; 20–28: moderate depression; 29–63: severe depression Sensitivity: 81%; Specificity: 92%
Profile of Mood States (POMS)	65 adjectives (5–point scale):	6 factors (Anger-Hostility; Confusion-Bewilderment; Depression-Dejection; Fatigue-Inertia; Tension-Anxiety; Vigor-Activity)	Short version available for cancersettings [99]
Patient Health Questionnaire PHQ-9	9 items (scored 0– 3, range 0–27)covering DSM criteria for MDD	Score 5–9: mild depression; 10–14 moderate depression; 15–19 moderately severe depression; 20–27 severe depression	Score ≥8: sensitivity 93%, specificity 81% PPV 25%, NPV 99% in cancer settings [100]
Demoralization scale (DS) Demoralization scale II (DS-II)	24 items on a 5-point Likert scale16 items on a 3-point Likert scale	Scores ≥30 high demoralization Scores 0–3: low demoralization; 4–10 middle demoralization; ≥11 high demoralization	DS and DS-II validation studies inprogress in cancer settings(e.g. Germany, Italy, Spain)
Subjective Incompetence Scale (SI)	12 items on a 0–3 Likert scale	Studies on threshold scores in progress	SI validation studies in progress incancer settings

Table 2. Main risk factors for depression in cancer patients.

Individual factors

• Family history of mood disorders [92]

• Personal psychiatric history (mood disorders, alcohol or drug addiction) [92]

• Personality traits (Type D, external locus of control, emotional repression, poor coping mechanisms, such as hopelessness-helplessness traits) [66–68]

Interpersonal and social risk factors:

• History of stressful life events (especially losses) [92]

• Loneliness (single, divorced, separated, widowed) [65]

• Social isolation [65]

• Low socio-economic status [5,7]

• Lack of social support [92]

Biological factors

• Type of cancer (e.g. lung, pancreas, head and neck, brain) [16,33,37,39]

• Advanced stage or metastatic disease [17,41,42]

• Uncontrolled physical symptoms (e.g. pain, nausea, vomiting, fatigue) [4]

• Inflammation factors (IL-interleukin 2; IL-6, TNF-α, and proinflammatory cytokines) [53,57]

• Treatment-related factors [5,7]

^ Immunological therapy (interferon-α)

^ Drugs [corticosteroids, methyldopa, β-blockers, antibiotics, clonidine, angiotensin-converting enzyme (ACE) inhibitors]

^ Anticonvulsants (phenytoin, levetiracetam)

^ Chemotherapy agents (vinblastine, vincristine, procarbazine, ciproterone)

Mitchell AJ, Meader N, Davies E, et al. Meta-analysis of screening and case finding tools for depression in cancer: evidence based recommendations for clinical practice on behalf of the Depression in Cancer Care consensus group. J Affect Disord. 2012;140:149–160.

 PubMed Web of Science ®Google Scholar

Mitchell AJ, Ferguson DW, Gill J, et al. Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis. Lancet Oncol. 2013;14:721–732.

 PubMed Web of Science ®Google Scholar

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. 2011;12:160–174.

 PubMed Web of Science ®Google Scholar

Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24:895–900.

 PubMed Web of Science ®Google Scholar

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. 2014;23:121–130.

 PubMed Web of Science ®Google Scholar

Robinson S, Kissane DW, Brooker J, et al. A systematic review of the demoralization syndrome in individuals with progressive disease and cancer: a decade of research. J Pain Symptom Manage. 2015;49:595–610.

 PubMed Web of Science ®Google Scholar

Rayner L, Price A, Hotopf M, et al. The development of evidence-based European guidelines on the management of depression in palliative cancer care. Eur J Cancer. 2011;47:702–712.

 PubMed Web of Science ®Google Scholar

Grassi L, Malacarne P, Maestri A, et al. Depression, psychosocial variables and occurrence of life events among patients with cancer. J Affect Disord. 1997;44:21–30.

 PubMed Web of Science ®Google Scholar

Yang Y-L, Liu L, Wang Y, et al. The prevalence of depression and anxiety among Chinese adults with cancer: a systematic review and meta-analysis. BMC Cancer. 2013;13:393.

 PubMed Web of Science ®Google Scholar

Vodermaier A, Millman RD. Accuracy of the Hospital Anxiety and Depression Scale as a screening tool in cancer patients: a systematic review and meta-analysis. Support Care Cancer. 2011;19:1899–1908.

 PubMed Web of Science ®Google Scholar

Carey M, Noble N, Sanson-Fisher R, et al. Identifying psychological morbidity among people with cancer using the Hospital Anxiety and Depression Scale: time to revisit first principles?. Psychooncology. 2012;21:229–238.

 PubMed Web of Science ®Google Scholar

Eaton WW, Smith C, Ybarra M, et al. : Center for Epidemiologic Studies Depression Scale: review and revision (CESD and CESD-R), in: M.E. Maruish (Ed.), The Use of Psychological Testing for Treatment Planning and Outcomes Assessment, Instruments for Adults (3rd ed.), 3, Lawrence Erlbaum, Mahwah, NJ, 2004, pp. 363–377.

 Google Scholar

Baker F, Denniston M, Zabora J, et al. A POMS short form for cancer patients: psychometric and structural evaluation. Psychooncology. 2002;11:273–281.

 PubMed Web of Science ®Google Scholar

Thekkumpurath P, Walker J, Butcher I, et al. Screening for major depression in cancer outpatients: the diagnostic accuracy of the 9-item patient health questionnaire. Cancer. 2011;117:218–227.

 PubMed Web of Science ®Google Scholar

Grassi L, Nanni MG, Caruso R. Emotional distress in cancer: screening policy, clinical limitations and educational needs. J Med Person. 2010;8:51–59.

 Google Scholar

Brandão T, Schulz MS, Matos PM. Psychological adjustment after breast cancer: A systematic review of longitudinal studies. Psychooncology. 2016;20: doi: 10.1002/pon.4230.

 Web of Science ®Google Scholar

Smith H. Depression in cancer patients: Pathogenesis, implications and treatment. Oncology Letters. 2015;9:1509–1514.

 PubMed Web of Science ®Google Scholar

Dauchy S, Dolbeault S, Reich M. Depression in cancer patients. EJC Suppl. 2013;11:205–215.

 PubMedGoogle Scholar

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. 2014;1:343–350.

 PubMed Web of Science ®Google Scholar

Lydiatt WM, Moran J, Burke WJ. A review of depression in the head and neck cancer patient. Clin Adv Hematol Oncol. 2009;7:397–403.

 PubMedGoogle Scholar

Boyd AD, Riba M. Depression and pancreatic cancer. J Natl Compr Canc Netw. 2007;5:113–116.

 PubMedGoogle Scholar

Hotopf M, Chidgey J, Addington-Hall J, et al. Depression in advanced disease: a systematic review Part 1. Prevalence and case finding. Palliat Med. 2002;16:81–97.

 PubMed Web of Science ®Google Scholar

Janberidze E, Hjermstad MJ, Haugen DF, EURO IMPACT, et al. How are patient populations characterized in studies investigating depression in advanced cancer? Results from a systematic literature review. J Pain Symptom Manage. 2014;48:678–698.

 PubMed Web of Science ®Google Scholar

Pasquini M, Biondi M. Depression in cancer patients: a critical review. Clin Pract Epidemiol Ment Health. 2007;3:2.

 PubMedGoogle Scholar

Reich M. Depression and cancer: recent data on clinical issues, research challenges and treatment approaches. Curr Opin Oncol. 2008;20:353–359.

 PubMed Web of Science ®Google Scholar

Myers JS. Proinflammatory cytokines and sickness behavior: implications for depression and cancer-related symptoms. Oncol Nurs Forum. 2008;35:802–807.

 PubMed Web of Science ®Google Scholar