While written accounts of delirium date back centuries, these older descriptions often depict the condition in a fatalistic light—as the harbinger of imminent death. Modern medicine allows for a more nuanced view of the diagnosis, treatment, and overall course of delirium.
Although ubiquitous across all medical specialties, delirium plays a prominent role in oncology. Patients are exposed to multiple modalities of treatment, such as chemotherapy and immunotherapy, surgery, and radiation, all of which can influence cognition in a fluctuating pattern. Chronic conditions often seen in cancer patients, such as pain, nausea, and anxiety, are also treated with potentially deliriogenic agents. While delirium is typically considered a condition of the acute medical setting, cancer patients may report it in the outpatient setting as well. Incidence estimates range from 43% in the general cancer population to 85% in patients in the terminal stages of their illness, making delirium one of the most common cancer comorbidities, although it often goes unrecognized.
The commonly accepted criteria for delirium, found in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), have remained relatively stable over time. These include an alteration in attention and awareness (Criterion A) that occurs within a span of hours to days, fluctuating in severity several times in the course of a day (Criterion B). There are also disturbances in other aspects of the patient’s mental state, which can include, but are not limited to, aphasia, amnesia, disorientation, visuospatial changes, and hallucinations (Criterion C). Finally, there should be clinical evidence that this presentation is directly related to some physiologic insult, including medication or withdrawal syndromes, as opposed to being due to a preexisting neurocognitive condition (Criteria D and E, respectively). In a phenomenological study of 100 palliative care patients with delirium, the most common disturbance was in attention (97%), followed by long- and short-term memory impairment (89% and 88%). Less common were disturbances in orientation (76%) or perception (50%). Thus, if physicians rely on the presence of hallucinations or disorientation, they can miss potentially treatable cases.
Of note, the DSM-5 criteria do not mention disruption in sleep cycle or changes in motor activity—frequent hallmarks of delirium—although these are described in the International Classification of Diseases, Tenth Revision (ICD-10) criteria. Furthermore, the DSM-5 criteria lack specifiers, such as the hyperactive subtype (characterized by disinhibition and often violent activity), the hypoactive subtype (a withdrawn, almost catatonic, state), and the mixed subtype. Despite these limitations, the DSM-5 criteria remain useful for their high inter-rater reliability.
Commonly used instruments for delirium screening include the 10-question Confusion Assessment Method (CAM), which is notable for its versatility: the CAM is available in a shortened four-item algorithm; there is a family-administered version, referred to as FAM-CAM, which makes it possible for families to screen for delirium; and finally, CAM-ICU has been specifically developed for delirium screening of patients in intensive care units who are unable to speak. The Memorial Delirium Assessment Scale (MDAS) is a rating instrument commonly used to monitor the progression of delirium, but it can also be employed for screening. The Short Blessed Test is a sensitive series of four weighted questions that can assess attention and orientation quickly and in multiple settings, although it is not specific enough to rule out other neurocognitive disorders.
In addition to understanding the criteria for a diagnosis of delirium, oncologists must maintain strong clinical vigilance. In one study that followed 771 cancer patients referred to palliative care for consultation, 33% met criteria for delirium when seen by a consultant, but the majority of these (61%) had not been diagnosed by the referring team. Similarly, in a case series of 60 cancer patients seen by consulting psychiatrists and ultimately diagnosed with delirium, 37% of the diagnoses had initially been missed.
Diagnosis of delirium in the cancer population can be challenging for several reasons. Cancer-related cognitive impairment is a common complaint among patients. It can be difficult to distinguish delirium from the more chronic alterations in attention, executive function, and energy associated both with cancer treatment and with the disease itself. Accordingly, it is useful to obtain collateral information from caretakers and family members to provide a clear chronology for events such as losing items in the house, getting lost, having difficulty with language and directions, displaying alterations in sleep, etc. Particular focus should be put on acuity and fluctuation in these symptoms, as well as on possible precipitating factors (eg, medications, constipation/urinary retention, abrupt changes in environment).
Mood and anxiety symptoms are also common comorbidities in cancer patients and can obfuscate the diagnosis of delirium. Major depressive disorder itself can impact cognition and concentration, particularly when it presents in its most severe form. However, even in patients with major depressive disorder, high clinical suspicion should be maintained for delirium, particularly in those without any significant psychiatric history prior to their cancer diagnosis. Psychiatrists are consulted frequently for depression when a patient appears to lose interest in his or her self-care or treatment, but they often find that the patient’s withdrawal is secondary to a hypoactive delirium.[9-11] Distinguishing between depression and hypoactive delirium is a particular challenge with older cancer patients.
1. de la Cruz M, Fan J, Yennu S, et al. The frequency of missed delirium in patients referred to palliative care in a comprehensive cancer center. Support Care Cancer. 2015;23:2427-33.
2. Breitbart W, Alici Y. Agitation and delirium at the end of life: “We couldn’t manage him.” JAMA. 2008;300:2898-910.
3. Meagher DJ, Moran M, Raju B, et al. Phenomenology of delirium: assessment of 100 adult cases using standardised measures. Br J Psychiatry. 2007;190:135-41.
4. Sepulveda E, Franco JG, Trzepacz PT, et al. Delirium diagnosis defined by cluster analysis of symptoms versus diagnosis by DSM and ICD criteria: diagnostic accuracy study. BMC Psychiatry. 2016;16:167.
5. Fadul N, Kaur G, Zhang T, et al. Evaluation of the Memorial Delirium Assessment Scale (MDAS) for the screening of delirium by means of simulated cases by palliative care health professionals. Support Care Cancer. 2007;15:1271-6.
6. Carpenter CR, Bassett ER, Fischer GM, et al. Four sensitive screening tools to detect cognitive dysfunction in geriatric emergency department patients: brief Alzheimer’s Screen, Short Blessed Test, Ottawa 3DY, and the caregiver-completed AD8. Acad Emerg Med. 2011;18:374-84.
7. Wada T, Wada M, Wada M, Onishi H. Characteristics, interventions, and outcomes of misdiagnosed delirium in cancer patients. Palliat Support Care. 2010;8:125-31.
8. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26:102-13.
9. Nicholas LM, Lindsey BA. Delirium presenting with symptoms of depression. Psychosomatics. 1995;36:471-9.
10. Marchington KL, Carrier L, Lawlor PG. Delirium masquerading as depression. Palliat Support Care. 2012;10:59-62.
11. Hosker C, Ward D. Hypoactive delirium. BMJ. 2017;357:j2047.
12. Farrell KR, Ganzini L. Misdiagnosing delirium as depression in medically ill elderly patients. Arch Intern Med. 1995;155:2459-64.
13. National Institute for Health and Care Excellence (NICE). Delirium: diagnosis, prevention and management (full guideline). July 2010. https://www.nice.org.uk/guidance/cg103. Accessed August 10, 2017.
14. Korc-Grodzicki B, Sun SW, Zhou Q, et al. Geriatric assessment as a predictor of delirium and other outcomes in elderly patients with cancer. Ann Surg. 2015;261:1085-90.
15. Kayser MS, Kohler CG, Dalmau J. Psychiatric manifestations of paraneoplastic disorders. Am J Psychiatry. 2010;167:1039-50.
16. Bentea G, Sculier C, Grigoriu B, et al. Autoimmune paraneoplastic syndromes associated to lung cancer: a systematic review of the literature: Part 3: neurological paraneoplastic syndromes, involving the central nervous system. Lung Cancer. 2017;106:83-92.
17. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15:391-404.
18. Schwarzbach CJ, Schaefer A, Ebert A, et al. Stroke and cancer: the importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke. 2012;43:3029-34.
19. Isenberg-Grzeda E, Alici Y, Hatzoglou V, et al. Nonalcoholic thiamine-related encephalopathy (Wernicke-Korsakoff syndrome) among inpatients with cancer: a series of 18 cases. Psychosomatics. 2016;57:71-81.
20. Isenberg-Grzeda E, Rahane S, DeRosa AP, et al. Wernicke-Korsakoff syndrome in patients with cancer: a systematic review. Lancet Oncol. 2016;17:e142-e148.
21. Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatry. 1996;153:231-7.
22. Hu H, Deng W, Yang H, Liu Y. Olanzapine and haloperidol for senile delirium: a randomized controlled observation. Chin J Clin Rehabil. 2006;10:188-90.
23. Tahir TA, Eeles E, Karapareddy V, et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. 2010;69:485-90.
24. Agar MR, Lawlor PG, Quinn S, et al. Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Intern Med. 2017;177:34-42.
25. Breitbart W, Alici Y. Evidence-based treatment of delirium in patients with cancer. J Clin Oncol. 2012;30:1206-14.
26. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Distress management. Version 1.2017. http://www.nccn.org/professionals/physician_gls/pdf/distress.pdf. Accessed July 24, 2017.