Depression in cancer patients: Pathogenesis, implications and treatment (Review)

  • Authors:
    • Hamish R. Smith
  • View Affiliations

  • Published online on: February 9, 2015     https://doi.org/10.3892/ol.2015.2944
  • Pages: 1509-1514
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Depression is a common comorbidity in cancer cases, affecting >10% of patients. A cancer diagnosis is life‑changing, and is a source of considerable psychological and emotional stress. Non‑pathological sadness may be a normal response to a cancer diagnosis, however, stress beyond the coping mechanisms of patients may result in major depressive disorder. The current review, in addition to the obvious psychosocial elements of depression, explores its biological mechanisms, including tissue damage, inflammatory mediators and the chronic stress response, and how these immune and endocrine pathways may underlie depression in cancer. Possible iatrogenic causes of depression in cancer are also explored. There is a strong need to identify and treat depression in cancer patients in order to increase quality of life and reduce mortality. The most popular clinical and potential future biochemical screening tools for depression in cancer are briefly discussed. The interventions used will vary for every patient, but may include psychosocial therapies or pharmacotherapy; however, a paucity of research on the most effective management of depression in cancer means the optimal combination of therapies is unknown. Selection of antidepressants should be carefully considered, given the common side effects of chemotherapy (such as nausea), and the necessity to avoid serious interactions, including reducing the effectiveness of chemotherapeutic drugs. The possible link between the chronic stress response, which may predispose patients to depression, and the risk of mortality from cancer is also explored. The complex interactions between the endocrine, nervous and immune systems, which continue to be elucidated, may offer the opportunity for the development of more rapid and efficacious treatments for depression in cancer in the future.

References

1 

Mishel MH, Hostetter T, King B and Graham V: Predictors of psychosocial adjustment in patients newly diagnosed with gynecological cancer. Cancer Nurs. 7:291–299. 1984. View Article : Google Scholar : PubMed/NCBI

2 

Linden W, Vodermaier A, Mackenzie R and Greig D: Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 141:343–351. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Brintzenhofe-Szoc KM, Levin TT, Li Y, Kissane DW and Zabora JR: Mixed anxiety/depression symptoms in a large cancer cohort: prevalence by cancer type. Psychosomatics. 50:383–391. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Colleoni M, Mandala M, Peruzzotti G, et al: Depression and degree of acceptance of adjuvant cytotoxic drugs. Lancet. 356:1326–1327. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Pinquart M and Duberstein PR: Depression and cancer mortality: a meta-analysis. Psychol Med. 40:1797–1810. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Satin JR, Linden W and Phillips MJ: Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer. 115:5349–5361. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Lemon J, Edelman S and Kidman AD: Perceptions of the “Mind-Cancer” Relationship Among the Public, Cancer Patients, and Oncologists. J Psychosoc Oncol. 21:43–58. 2004. View Article : Google Scholar

8 

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edition. American Psychiatric Publishing; Arlington, VA: 2013

9 

Sneeuw KCA, Aaronson NK, van Wouwe MCC, et al: Prevalence and screening of psychiatric disorder in patients with early stage breast cancer. Qual Life Res. 2:50–51. 1993.

10 

Okamura M, Yamawaki S, Akechi T, et al: Psychiatric disorders following first breast cancer recurrence: prevalence, associated factors and relationship to quality of life. Jpn J Clin Oncol. 35:302–309. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Ciaramella A and Poli P: Assessment of depression among cancer patients: the role of pain, cancer type and treatment. Psychooncology. 10:156–165. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Ng CG, Boks MP, Zainal NZ and de Wit NJ: The prevalence and pharmacotherapy of depression in cancer patients. J Affect Disord. 131:1–7. 2011. View Article : Google Scholar

13 

Allen R, Newman SP and Souhami RL: Anxiety and depression in adolescent cancer: findings in patients and parents at the time of diagnosis. Eur J Cancer. 33:1250–1255. 1997. View Article : Google Scholar : PubMed/NCBI

14 

von Essen L, Enskär K, Kreuger A, et al: Self-esteem, depression and anxiety among Swedish children and adolescents on and off cancer treatment. Acta Paediatr. 89:229–236. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Boyes AW, Girgis A, Zucca AC and Lecathelinais C: Anxiety and depression among long-term survivors of cancer in Australia: results of a population-based survey. Med J Aust. 190:S94–S98. 2009.PubMed/NCBI

16 

Spiegel D, Sands S and Koopman C: Pain and depression in patients with cancer. Cancer. 74:2570–2578. 1994. View Article : Google Scholar : PubMed/NCBI

17 

Akechi T, Nakano T, Akizuki N, et al: Somatic symptoms for diagnosing major depression in cancer patients. Psychosomatics. 44:244–248. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Pasquini M, Speca A, Mastroeni S, et al: Differences in depressive thoughts between major depressive disorder, IFN-alpha-induced depression, and depressive disorders among cancer patients. J Psychosom Res. 65:153–156. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Musselman DL, Miller AH, Porter MR, et al: Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry. 158:1252–1257. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Nadjar A, Bluthé RM, May MJ, et al: Inactivation of the cerebral NFkappaB pathway inhibits interleukin-1beta-induced sickness behavior and c-Fos expression in various brain nuclei. Neuropsychopharmacology. 30:1492–1499. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Zigmond AS and Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 67:361–370. 1983. View Article : Google Scholar : PubMed/NCBI

22 

Jehn CF, Kuehnhardt D, Bartholomae A, et al: Biomarkers of depression in cancer patients. Cancer. 107:2723–2729. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Bianchi ME: DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 81:1–5. 2007. View Article : Google Scholar

24 

Aggarwal BB, Shishodia S and Sandur SK: Inflammation and cancer: how hot is the link? Biochem Pharmacol. 72:1605–1621. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Bierhaus A, Wolf J, Andrassy M, et al: A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci USA. 100:1920–1925. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Szabo S, Gould TD and Manji HK: Introduction to neurotransmitters, receptors, signal transduction, and second messengers in psychiatric disorders. The American Psychiatric Publishing Textbook of Psychopharmacology. Schatzberg AF and Nemeroff CB: 3rd edition. American Psychiatric Publishing; Washington DC: pp. 3–51. 2004

27 

Raison CL, Capuron L and Miller AH: Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 27:24–31. 2006. View Article : Google Scholar

28 

Zhu CB, Carneiro AM, Dostmann WR, Hewlett WA and Blakely RD: p38 MAPK activation elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process. J Biol Chem. 280:15649–15658. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Holsboer F and Ising M: Central CRH system in depression and anxiety - evidence from clinical studies with CRH1 receptor antagonists. Eur J Pharmacol. 583:350–357. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Duman RS and Monteggia LM: A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 59:1116–1127. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Felger JC, Mun J, Kimmel HL, Nye JA, et al: Chronic interferon-α decreases dopamine 2 receptor binding and striatal dopamine release in association with anhedonia-like behaviour in nonhuman primates. Neuropsychopharmacology. 38:2179–2187. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Felger JC, Li L, Marvar PJ, et al: Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine concentrations. Brain Behav Immun. 31:153–160. 2013. View Article : Google Scholar :

33 

Dantzer R, O’Connor JC, Freund GG, et al: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 9:46–56. 2008. View Article : Google Scholar

34 

DeMyer MK, Shea PA, Hendrie HC and Yoshimura NN: Plasma tryptophan and five other amino acids in depressed and normal subjects. Arch Gen Psychiatry. 38:642–646. 1981. View Article : Google Scholar : PubMed/NCBI

35 

Myint AM and Kim YK: Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses. 61:519–525. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Sapolsky RM: The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry. 48:755–765. 2000. View Article : Google Scholar : PubMed/NCBI

37 

Pace TW, Hu F and Miller AH: Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun. 21:9–19. 2007. View Article : Google Scholar

38 

Pavlov VA and Tracey KJ: The cholinergic anti-inflammatory pathway. Brain Behav Immun. 19:493–499. 2005. View Article : Google Scholar : PubMed/NCBI

39 

Besedovsky HO and del Rey A: Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev. 17:64–102. 1996. View Article : Google Scholar : PubMed/NCBI

40 

Wang X: Interleukin 1alpha (IL-1alpha) induced activation of p38 mitogen-activated kinase inhibits glucocorticoid receptor function. Mol Psychiatry. 9:65–75. 2004. View Article : Google Scholar

41 

Raison CL and Miller AH: When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. 160:1554–1565. 2003. View Article : Google Scholar : PubMed/NCBI

42 

Patten SB and Barbui C: Drug-induced depression: a systematic review to inform clinical practice. Psychother Psychosom. 73:207–215. 2004. View Article : Google Scholar : PubMed/NCBI

43 

Fann JR, Thomas-Rich AM, Katon WJ, et al: Major depression after breast cancer: a review of epidemiology and treatment. Gen Hosp Psychiatry. 30:112–126. 2008. View Article : Google Scholar : PubMed/NCBI

44 

Liu L, Fiorentino L, Natarajan L, et al: Pre-treatment symptom cluster in breast cancer patients is associated with worse sleep, fatigue and depression during chemotherapy. Psychooncology. 18:187–194. 2009. View Article : Google Scholar :

45 

Koenig HG, Shelp F, Goli V, et al: Survival and health care utilization in elderly medical inpatients with major depression. J Am Geriatr Soc. 37:599–606. 1989.PubMed/NCBI

46 

Misono S, Weiss NS, Fann JR, et al: Incidence of suicide in persons with cancer. J Clin Oncol. 26:4731–4738. 2008. View Article : Google Scholar : PubMed/NCBI

47 

Michael Maes M, Meltzer HY, Stevens W, et al: Natural killer cell activity in major depression: relation to circulating natural killer cells, cellular indices of the immune response, and depressive phenomenology. Prog Neuropsychopharmacol Biol Psychiatry. 18:717–730. 1994. View Article : Google Scholar

48 

Lutgendorf SK, Lamkin DM, DeGeest K, et al: Depressed and anxious mood and T- cell cytokine expressing populations in ovarian cancer patients. Brain Behav Immun. 22:890–900. 2008. View Article : Google Scholar : PubMed/NCBI

49 

Saul AN, Oberyszyn TM, Daugherty C, et al: Chronic stress and susceptibility to skin cancer. J Natl Cancer Inst. 97:1760–1767. 2005. View Article : Google Scholar : PubMed/NCBI

50 

Feng Z, Liu L, Zhang C, et al: Chronic restraint stress attenuates p53 function and promotes tumorigenesis. Proc Natl Acad Sci USA. 109:7013–7018. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Hassan S, Karpova Y, Baiz D, et al: Behavioral stress accelerates prostate cancer development in mice. J Clin Invest. 123:874–886. 2013.PubMed/NCBI

52 

Giese-Davis J, Collie K, Rancourt KM, et al: Decrease in depression symptoms is associated with longer survival in patient with metastatic breast cancer: a secondary analysis. J Clin Oncol. 29:413–420. 2011. View Article : Google Scholar :

53 

Li M, Fitzgerald P and Rodin G: Evidence-based treatment of depression in patients with cancer. J Clin Oncol. 30:1187–1196. 2012. View Article : Google Scholar : PubMed/NCBI

54 

Norman TR: The new antidepressants - mechanisms of action. Aust Prescr. 22:106–108. 1999.

55 

Laoutidis ZG and Mathiak K: Antidepressants in the treatment of depression/depressive symptoms in cancer patients: a systematic review and meta-analysis. BMC Psychiatry. 13:1402013. View Article : Google Scholar : PubMed/NCBI

56 

Lloyd-Williams M, Payne S, Reeve J and Kolamunnage Dona R: Antidepressant medication in patients with advanced cancer - an observational study. QJM. 106:995–1001. 2013. View Article : Google Scholar : PubMed/NCBI

57 

Olin J and Masand P: Psychostimulants for depression in hospitalized cancer patients. Psychosomatics. 37:57–62. 1996. View Article : Google Scholar : PubMed/NCBI

58 

Stefanczyk-Sapieha L, Oneschuk D and Demas M: Intravenous ketamine “burst” for refractory depression in a patient with advanced cancer. J Palliat Med. 11:1268–1271. 2008. View Article : Google Scholar : PubMed/NCBI

59 

Berman RM, Cappiello A, Anand A, et al: Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 47:351–354. 2001. View Article : Google Scholar

60 

Caraci F, Crupi R, Drago F and Spina E: Metabolic drug interactions between antidepressants and anticancer drugs: focus on selective serotonin reuptake inhibitors and hypericum extract. Curr Drug Metab. 12:570–577. 2011. View Article : Google Scholar : PubMed/NCBI

61 

Borges S, Desta Z, Li L, et al: Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implications for optimization of breast cancer treatment. Clin Pharmacol Ther. 80:61–74. 2006. View Article : Google Scholar : PubMed/NCBI

62 

Whitten DL, Myers SP, Hawrelak JA and Wohlmuth H: The effect of St John’s wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 62:512–526. 2006. View Article : Google Scholar : PubMed/NCBI

63 

Yap KY, Tay WL, Chui WK and Chan A: Clinically relevant drug interactions between anticancer drugs and psychotropic agents. Eur J Cancer Care (Engl). 20:6–32. 2011. View Article : Google Scholar

64 

Sloman R: Relaxation and imagery for anxiety and depression control in community patients with advanced cancer. Cancer Nurs. 25:432–435. 2002. View Article : Google Scholar : PubMed/NCBI

65 

Osborn RL, Demoncada AC and Feuerstein M: Psychosocial interventions for depression, anxiety, and quality of life in cancer survivors: meta-analyses. Int J Psychiatry Med. 36:13–34. 2006. View Article : Google Scholar : PubMed/NCBI

66 

Hopko DR, Armento ME, Robertson SM, et al: Brief behavioural activation and problem-solving therapy for depressed breast cancer patients: randomized trial. J Consult Clin Psychol. 79:834–849. 2011. View Article : Google Scholar : PubMed/NCBI

67 

Feroes DL, Lane L, Ciarrochi J and Blackledge JT: Acceptance and Commitment Therapy (ACT) for improving the lives of cancer patients: a preliminary study. Psychooncology. 22:459–464. 2013.

68 

Barsevick AM, Sweeney C, Haney E and Chung E: A systematic qualitative analysis of psychoeducational interventions for depression in patients with cancer. Oncol Nurs Forum. 29:73–87. 2002. View Article : Google Scholar : PubMed/NCBI

69 

Craft LL, Vanlterson EH, Helenowski IB, et al: Exercise effects on depressive symptoms in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 21:3–19. 2012. View Article : Google Scholar :

Related Articles

Journal Cover

April 2015
Volume 9 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Smith, H.R. (2015). Depression in cancer patients: Pathogenesis, implications and treatment (Review). Oncology Letters, 9, 1509-1514. https://doi.org/10.3892/ol.2015.2944
MLA
Smith, H. R."Depression in cancer patients: Pathogenesis, implications and treatment (Review)". Oncology Letters 9.4 (2015): 1509-1514.
Chicago
Smith, H. R."Depression in cancer patients: Pathogenesis, implications and treatment (Review)". Oncology Letters 9, no. 4 (2015): 1509-1514. https://doi.org/10.3892/ol.2015.2944