Perhaps the most challenging task in addressing depression and anxiety in seriously ill patients is to be able to distinguish among the many different conditions that are marked by these symptoms. For example, while depressed mood is the hallmark of MDD, this symptom may also characterize a variety of other conditions, including adjustment disorder, dysthymia, grief, and demoralization syndrome. The features that distinguish these conditions are described in detail later and summarized in Table 6.1. Since treatment approaches may differ, it can be important to distinguish one condition from another.

Major depression is the condition against which others are compared [10]. The disorder is characterized by the presence of a major depressive episode,¹ which occurs when a patient experiences either a depressed mood or anhedonia (loss of interest in pleasurable activity), nearly every day, over a period of at least 2 weeks.² In addition, in major depression, the depressed mood or anhedonia is accompanied by a number of cognitive or somatic symptoms. Cognitive changes may include poor concentration or indecision, as well as thoughts of worthlessness, hopelessness, guilt, or death. Somatic symptoms may include changes in appetite or weight, changes in sleep, decreased energy, or changes in psychomotor activity. As with all psychiatric illnesses, significant functional impairment—major problems in relationships, at work, or in self-care—needs to be present in order for the condition to be considered pathological.

Particularly in patients with serious illness and perhaps even more so in the acute care setting, differentiating normal states of sadness from major depression can be quite challenging, even for experienced clinicians. Patients with advanced illness will commonly experience episodes of intense sadness; many endure periods of anhedonia, low motivation, and even hopelessness; and it should be expected that seriously ill patients will also contemplate death. Taken individually, none of these phenomena should be assumed to indicate the presence of pathological depression. Similarly, the somatic dimensions of major depression (e.g., changes in sleep, low energy, changes in weight and appetite) frequently overlap with the physical symptoms seen in advanced medical illnesses, and so these alone are not reliable indicators of depression in this population. Instead, experts in palliative care psychiatry give greater weight to the emotional and cognitive symptoms of depression, as well as changes in mood from baseline, and the intensity and time course of symptoms [12]. Thus, feelings of worthlessness, hopelessness, guilt, or thoughts of suicide are likely to indicate major depression, whereas changes in appetite or level of energy may represent symptoms of the underlying medical illness. Similarly, true anhedonia, in which the patient is disinterested in the things that once gave pleasure (and not simply unable to engage in those activities due to physical limitations), helps to identify major depression.

While major depression is the illness most clinicians have in mind when they refer to a patient as being “clinically depressed,” several other important conditions may overlap with, or may be mistaken for, MDD. Adjustment disorder occurs in the context of an identifiable stressor, in which the patient experiences marked distress (in the form of depression, anxiety, or behavioral disturbances) to a degree in excess of the intensity of the stressor. In theory, the approach to “treatment” in adjustment disorder is nonpharmacologic, aimed at bolstering coping strategies or resolving/removing the stressor. Grief, the emotional experience associated with a significant loss, is also a distinct experience from major depression, though the two conditions have in common the experience of a depressed mood [13]. Of note, in the most recent iteration of the Diagnostic and Statistic Manual of Mental Disorders (DSM), the “bereavement exception” was removed from the diagnosis of MDD, so that even in the setting of bereavement, MDD should be diagnosed (and treatment considered) if criteria are met [10]. This distinction is important because the general approach to addressing grief, in the absence of major depression, should be with supportive therapeutic interventions and not drug therapy, though medication for specific symptoms, such as insomnia, can be helpful for brief periods. Demoralization syndrome captures a suite of psychological phenomena commonly seen in patients with advanced, serious illnesses, which may overlap with major depression [11]. At the core of demoralization syndrome is a sense of subjective incompetence, arising from the loss of purpose and meaning that may result from a serious medical illness. As distinct from depression, in which anhedonia robs patients of the ability to experience pleasure, demoralization syndrome is marked by profound hopelessness, robbing patients of the ability to imagine a fulfilling future. Also, the demoralized patient retains the reactivity of mood (i.e., they can experience happiness in relation to positive events), which is frequently lost in depression. There is considerable debate, beyond the scope of this chapter, as to whether or not demoralization syndrome can be reliably distinguished from major depression.

Finally, two common neurocognitive disorders, delirium and dementia, may also sometimes be mistaken for depression, particularly when marked by social withdrawal, psychomotor retardation, and abulia (diminished motivation). In both conditions, however, the predominant symptom is a significant cognitive disturbance, with an onset that is generally insidious (in the case of dementia), or acute/subacute (in the case of delirium). While cognitive deficits are seen in major depression, these tend to arise only after the emergence of changes in mood or the development of anhedonia.