What Treatments Are Effective for Depression in Palliative Care Settings?

Defining Depression in Advanced Illness

Psychological distress of any kind is a major cause of suffering among patients with advanced, life-threatening illness and is highly associated with decreased quality of life. More than 60% of cancer patients report experiencing distress. Understanding the causes of this normative distress associated with illness and differentiating it from distress associated with psychiatric disorders requires an appreciation of the clinical characteristics and prevalence of psychiatric disorders. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) outlines criteria for the spectrum of depressive illnesses palliative care clinicians may encounter. Patients diagnosed with a serious illness may experience adjustment disorders, which are emotional or behavioral symptoms that develop over a 3-month period. This can be characterized by depressed mood, anxiety, or conduct disturbances. The source of the stress can be identified and leads to clinically significant behavioral and emotional changes that are out of proportion to the severity or intensity of the stressor and causes significant impairment in functioning. The symptoms often resolve within a six-month period or once the stressor is removed, though this does not typically apply in the palliative care setting.

A major depressive disorder is diagnosed when a person has at least five of the following symptoms daily, almost all day, over a minimum of a two-week period, and at least one of the symptoms is a depressed mood or loss of interest or pleasure: significant unintentional weight loss or gain, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness or guilt, diminished ability to think or concentrate, and suicidal ideation. The symptoms must also cause impairment in daily functioning and not be attributable to another medical condition or substance to meet these diagnostic criteria, and these episodes may be defined as a single episode or a recurrent disorder.

For palliative care patients, it is important to distinguish recurrent thoughts of death or dying from the desire to actively hasten death and whether or not either is driven by depression versus an interest in end-of-life options to avoid what the patient defines as unacceptable suffering. As many as 59% of patients requesting medical aid in dying meet criteria for depression. Lloyd-Williams carried out a prospective study to evaluate incidence of suicidal ideation in a palliative care population, mostly with very late-stage disease, and found that 3% had such thoughts often, 10% experienced them sometimes, 17% hardly ever experienced them, and 70% never had thoughts of self-harm. Younger patients were more likely to report suicidal thoughts.

Differentiation between these types of distress, as well as addressable underlying medical causes (e.g., hypothyroidism), is critical for deciding upon beneficial interventions that target the causes of this distress. For some patients, there is a clear relationship between their medical condition (or its treatments) and the development of depressive symptoms, such as Huntington’s disease, Parkinson’s disease, hypothyroidism, Cushing’s disease, and cerebrovascular accidents. Thus a wide approach to differential diagnosis that includes psychiatric, medication, and physiological causes should be taken. There exists a wide variability in reported rates of depression in this population explained by the lack of agreement on appropriate criteria for the diagnosis of depression in medically ill populations, differences in patient populations evaluated (both in relation to disease and staging), and variation in types and quality of assessment methods used. However, studies using structured (gold-standard) psychiatric interviews suggest prevalence ranges of 5% to 26% for major depression, and recent reviews suggest that the median prevalence of major depression in patients with “advanced disease” is about 15%. Research by Derogatis and colleagues which used the DSM-III diagnostic system showed that 47% of patients with cancer (all types, all stages) fulfilled diagnostic criteria for a psychiatric disorder. Of those 47%, 68% had adjustment disorders with depressed or anxious mood, 13% had major depression, and 8% had organic mental disorders such as dementia. Akechi and colleagues, in a prospective study using the Structured Clinical Interview for DSM-IIIR in a Japanese palliative care setting, found that 16% of patients had an adjustment disorder and 7% had major depression. More recent data using the Structured Clinical Interview for DSM-IV and including diverse patient populations with advanced cancer showed that 12% of the patients met criteria for a major psychiatric disorder: 7% major depression and 11% minor depression (defined as meeting two to four impairment criteria, one of which was depressed mood or lack of interest/pleasure in activities). More than one-third of patients with a psychiatric diagnosis met criteria for two or more diagnoses.

Prevalence rates and intervention outcomes of depression in palliative care patients range widely, depending on diagnostic criteria used and patient population studied. Ranges of up to 42% of major depression have been reported in palliative medicine settings, and rates of major depression range as high as 38% among cancer patients. Among those with cancer, the highest rates are reported in patients with cancers of the pancreas, oropharynx, and breast, though no causative relationships have been established.

The prevalence of depression in patients with advanced cancer, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and other end-organ failure tend to be more alike than different. Like cancer patients, those with other medical illnesses have elevated rates of major depression. Patients seeking to stop dialysis have rates of major depression between 5% and 25%; those with end-stage heart disease are reported to have prevalence rates of 36% for major depression and 22% for minor depression. Patients with CHF and COPD were found to have higher rates of depression than a population of cancer patients with similar estimated survival estimates. Similar rates of depression prevalence and worsening are found in youth awaiting or receiving organ transplants with higher life-time psychotropic usage compared to general youth populations. Patients with lung transplants have high rates of depressive symptoms, and inadequately treated depression has been found to be independently associated with decreased survival times.

Prevalence rates of depression appear to increase as patients become more ill. In a longitudinal study of patients with heart failure, worsening symptoms of depression were associated with hospitalizations for heart disease and death. Several studies suggest that the prevalence of depression in cancer has declined over the past 20 years, perhaps related to improvements in medical care, outcomes, and destigmatization of the diagnosis of cancer.

Rates of Mental Health Service Use and Intervention

A small number of studies have examined how clinicians assess and manage mental health issues in patients with advanced disease. Data suggest that palliative care clinicians and oncologists tend to under-recognize and underestimate the severity of patients’ depression. An older study reported that only about 3% of end-stage cancer patients were receiving antidepressant medications. One study of more than 1,000 patients receiving palliative care demonstrated that only 10% of patients received an antidepressant, and of those, 76% of antidepressants were prescribed during the last two weeks of life. Lottick and colleagues found that nearly half of patients with advanced cancer who met criteria for psychiatric illness did not receive mental health services, and that non-White patients were significantly less likely to receive mental health care than White patients. Fewer than half of depressed patients with advanced heart disease receive treatment for depression. Although major depression is still untreated or undertreated in patients with advanced illness, there are indications that palliative care physicians are becoming more aware of the need to screen and treat patients for depression. Lawrie and colleagues found that 73% of palliative care physicians routinely assess patients for depression, 75% prescribed selective serotonin reuptake inhibitors (SSRIs), 25% prescribed tricyclic antidepressants, 6% prescribed psychostimulants, and 3% prescribed St. John’s wort. When asked whether they would prescribe complementary or psychological therapies for depression, 35% reported that they would refer patients for aromatherapy, and only 8% would refer for counseling.