Background Diagnosing and providing treatment for a major depressive episode in patients with advanced cancer can improve quality of life. However, diagnosing major depression in advanced cancer can be complicated by the fact that many cancer symptoms overlap with the somatic symptoms of depression. Concerned family members might project their own anticipatory grief onto the patient or misinterpret cancer-associate clinical signs such as loss of appetite or functional decline as depression and label patients as depressed when they may not be. Furthermore, although depressive thoughts and symptoms may be present in up to 15-50% of cancer patients, only 5% to 20% will meet diagnostic criteria for major depressive disorder. Clinical dilemma in determining when it is appropriate to add pharmacotherapies for depressive symptoms or whether reflective listening and exploration of the patient’s concerns may be the only needed intervention are common.

Assessment Clinicians often rely more on the psychological or cognitive symptoms of depression (worthlessness, hopelessness, excessive guilt, and suicidal ideation) than the physical/somatic signs (weight loss, sleep disturbance) when making a diagnosis of major depressive disorder in patients with advanced cancer. Endicott has proposed substituting somatic criteria with affective criteria when evaluating depression in advanced cancer patients:

Physical/somatic symptoms…

1. Change in appetite/weight
2. Sleep disturbance
3. Fatigue, loss of energy
4. Diminished ability to think or concentrate

…are replaced by psychological symptoms

1. Tearfulness, depressed appearance
2. Social withdrawal, decreased talkativeness
3. Brooding, self-pity, pessimism
4. Lack of reactivity, blunting

Screening tools The Association of Palliative Medicine Science Committee performed a thorough assessment of available screening tools and rating scales for depression in palliative care. While they found that commonly used tools such as the Edinburgh Depression Scale and the Hospital Anxiety and Depression Scale have validated cut-off thresholds for palliative care patients, the depression screening tool with the highest sensitivity, specificity and positive predictive value was the single question: “Are you feeling down, depressed, or hopeless most of the time over the last two weeks?” Adding a second question regarding the presence of anhedonia may slightly improve sensitivity and specificity: “Have you experienced loss of interest in things or activities you would normally enjoy?”

Other etiologies Medication side effects from commonly used therapeutics in this patient population, like chemotherapeutic agents, opioids, benzodiazepines or glucocorticoids, can mimic the symptoms and signs of depression. Clinicians should be especially aware of hypoactive delirium in the differential diagnosis of depressive symptoms in cancer patients since its prevalence may reach up to 90% of terminally ill patients with cancer.

Summary: Symptoms of depression can overlap with normal aspect of the dying process. See Fast Fact #43 for a complete description of anticipatory grief and how to differentiate from major depression. See Fast Fact #146 on screening for depression in palliative care.

Teaching point: The key indicators of depression in the terminally ill are patient self-report of:

• Pervasive depressive feelings,
• Persistent feelings of hopelessness and worthless;
• Anhedonia;
• Suicidal ideation.

References

1. Endicott J. Measurement of depression patients with cancer. Cancer. 1983; 53:2243-8.
2. Block SD. Assessing and managing depression in the terminally ill. Ann Inter Med. 2000; 132:209-217.
3. Chochinov H, et al. Prevalence of depression in the terminally ill: effects of diagnostic criteria and symptom threshold judgments. Am J Psychiatry 1994;151:537-40.
4. Spiller JA, Keen JC. Hypoactive delirium: assessing the extent of the problem for inpatient specialist palliative care. Palliative Med 2006;20:17-23.
5. Williams ML, Spiller J. Which depression screening tools should be used in palliative care. Pall Med 2003;17:40-43.
6. Chochinov HM, et al. “Are you depressed?” Screening for depression in the terminally ill. Am J Psychiatry 1997;154:674-6.
7. Mitchell AJ, 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 Disorders 2012 Oct; 140(2): 149-60.
8. Grassi L, et al. Anxiety and Depression in adult cancer patients: European Society for Medical Oncology Clinical Practice Guideline. ESMO Open. 2023 April; 8(2):101155.
9. Meyer Z, et al. The Utility of the Brief Edinburgh Depression Scale in assessing severity of depression in advanced cancer patients. BJPsych 2021 June; 7(suppl):S42.

Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published July 2005; 3rd Edition May 2015; 4th Edition reviewed and updated by Kerry A Case MD in June 2024.
Conflicts of Interest: None to report.