The Assessment of Depressive Syndromes Adriana P. Hermida and William M. McDonald

THE SYNDROME OF LATE-LIFE DEPRESSION

To accurately assess the depressed older adult, the clinician must consider the range of depressive disorders from the more severe major depression to the subsyndromal depressive disorders. Depressive disorders include the mood disorders outlined in the Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV): major depressive disorder, dysthymic disorder, mood disorder due to a general medical condition, substance-induced mood disorder, bipolar disorder, mood disorder not otherwise specified (which include the minor and subsyndromal depression) and adjustment disorder.

Major depression is distinguished from the other mood disorders by the severity and persistence of symptoms, which by definition have lasted for at least two weeks and are associated with significant impairment in an individual’s social, occupational or other

important areas of functioning. Symptoms of major depression comprise depressed mood and/or anhedonia and associated neurovegetative and cognitive symptoms, including significant weight loss/weight gain or decreased/increased appetite, insomnia or hypersomnia, psy- chomotor agitation or retardation, diminished ability to think or concentrate, feelings of worthlessness or excessive inappropriate guilt, and recurrent thoughts of death or suicide.

Specifiers describing the quality of the current episode include melancholic, atypical and catatonic features. Melancholic features consist of lack of mood reactivity to pleasurable stimuli, diurnal variation in mood (i.e. depression worse in the morning), early morning awakening, psychomotor retardation or agitation, significant weight loss or anorexia and excessive or inappropriate guilt. A melancholic depression may be associated with specific neuroanatomic changes¹⁷, and may affect response to antidepressants^18-21, electroconvulsive therapy (ECT)^22,23 and psychotherapy^24,25. Atypical features include mood reactivity, increased appetite or weight gain, hypersomnia, leaden paralysis and extreme sensitivity to interpersonal rejection. Atypical depression in the elderly has been shown to respond preferentially to monoamine oxidase inhibitors (MAOIs) although the MAOIs may be more difficult to use in this population^15,26. The specifier catatonic features is appropriate when the clinical picture is characterized by marked psychomotor disturbances that involve motoric immobility, excessive motor activity, extreme negativism, mutism, peculiarities of voluntary movements, echolalia and echopraxia. Motoric immobility can be manifested by cataplexy or stupor. Catatonic states have been found to occur in 5-9% of psychiatric inpatients. Among inpatients, 25 -50% of catatonic states occur in association with mood disorders, 10-15% in association with schizophrenia, and the remainder in association with other mental disorders and a wide variety of medical conditions²⁷.

An additional specifier of major depression in the DSM-IV criteria is a seasonal pattern, which is associated with the onset and remission of major depressive episodes at characteristic times of the year. This pattern of onset and remission of episodes must have occurred during the past two years.

In the DSM-IV, depression is subtyped according to whether the mood disturbance is associated with psychotic symptoms. Psychotic symptoms in major depression are more likely to be mood-congruent (i.e. delusions or hallucinations of a depressive nature). Psychotic depression may be more common in late life. Many elderly patients with psychosis develop delusions of poverty, somatic delusions or persecutory ideations^28,29. Hallucinations of derogatory voices are rare. Known precipitants of psychotic symptoms in the elderly include personal trauma, physical illness and certain medications such as corticosteroids and anti-parkinsonian medications.

Subsyndromal depressions (SSDs) include minor depression, dys- thymia and syndromal depression that does not meet the criteria for major depression. SSDs are characterized by depressive symptoms that do not meet full criteria for a major depression but are associated with depressed mood and significant disability³⁰. SSD is common and associated with significant impairment in a number of areas of social and occupational functioning and an increased risk of developing syndromal major depression^31,32. Minor depression is a mood disorder that does not meet full criteria for major depressive disorder but which is associated with at least two depressive symptoms that are sustained for a period of two weeks (although not necessarily every day) without the degree of impairment in major depression. Technically a patient with minor depression would be coded as ‘Depression, not otherwise specified’ or NOS since minor depression is a research diagnosis. Research, much of it in primary care clinics, supports the validity of minor depression as a distinct clinical entity³¹. Dysthymic disorder (dysthymia) is defined as a chronic low-grade depression, which lasts for at least two years. Personality styles and the individual’s ability to cope with changing life situations may predispose the individual to develop a dysthymic disorder (see Chapter 104) and older adults with changing roles and life conditions may be particularly prone to dysthymia. Additionally, dysthymic disorder may develop secondary to a medical disorder, anxiety disorder or somati- zation disorder. Dysthymia preceding a major depressive episode has been shown to predict a poor outcome to treatment³³. Phenomenolog- ically, SSD is the ‘grey’ zone between syndromal major depression and depressive symptoms. In geriatric psychiatry, depression is often defined as a spectrum rather than a dichotomy. There is increasing evidence that elderly subjects meeting the criteria for SSD have levels of cognitive and functional impairment intermediate between elders who are not depressed and those with major depression³⁴. Nevertheless, patients with SSD demonstrate significant disability, are more likely to have persistent depressive symptoms which worsen over a year, be at a higher risk of developing major depression, and benefit from somatic treatments and psychotherapy^25,35. Clearly, future research is needed to clarify the prevalence and treatment response of SSD in order to target appropriate treatments.

Substance-induced mood disorder is a prominent and persistent disturbance in mood that is judged to be due to the direct physiological effects of a substance such as excessive alcohol use. Alcohol abuse in older adults is common and may go for years misdiagnosed³⁶. The elderly are particularly prone to substance-induced mood disorders because of chronic and often excessive use of over-the-counter medications mixed with prescription medications^37,38. Increasingly the elderly are using herbal medications and often the effects of herbal medications are unknown, particularly in combination with other drugs³⁹.

The diagnosis of adjustment disorder with depressed mood is appropriate for an elderly patient adjusting to severe changes in lifestyle and the loss of loved ones. In the DSM-IV, the patient is not classified with an adjustment disorder unless his/her reaction is considered maladaptive and the level of impairment is significantly severe, and greater than what would be normally expected. Whether the elderly subject’s reaction to these stressors is classified as a disorder is a clinical judgement. Several common life events that may prove to be stressors in the elderly include retirement, financial problems, living in high crime areas, physical illness, the death of a spouse and moving to an institutional setting. Yet older adults also may also be protected from stress as those who survive into old age are more likely to have relatively more socioeconomic security and the benefit of the wisdom that can come with older age⁴⁰. Regardless, the clinician should observe the patient diagnosed with adjustment disorder longitudinally for the development of symptoms of a major depression if the individual’s reaction to stress is persistent or severe.

The symptom profile of older patients with depression has also been described as qualitatively distinct from that of younger adults. Depressed elderly patients are more likely to show cognitive changes, somatic symptoms, fatigue and loss of interest as opposed to depressed mood and guilt^41,42. Other researchers emphasize that these differing presentations are the result of accompanying cognitive changes with ageing and co-morbid medical illness, which are more likely to occur in older depressed patients, and that depressed elderly patients without concomitant medical illnesses have presentations similar to younger subjects⁴³. Support for this latter view has been provided by Blazer and his colleagues⁴⁴, who compared depressive symptoms in a group of middle-aged (35-50-year-old) and older (60-year-old) inpatients with melancholic depression. The symptom profiles of these patients were markedly similar to the elderly, differing only in their more frequent reporting of weight loss and less frequent suicidal thoughts. Finally, Blazer discusses some of the misconceptions of depression in the elderly, pointing out that, as discussed above, symptomatically there is little difference when compared to adult early-onset depression.

CO-MORBID MEDICAL DISEASE

A variety of medical illnesses are associated with depressive symptoms. Mood disorder due to a general medical condition is a persistent disturbance in mood due to the direct physiological effect of a general medical condition. In the geriatric population the differentiation between mood disorder due to a general medical condition and depression as a psychological reaction to the disability due to the medical illness is challenging.

There are basically two different approaches to defining depression in medically ill patients. The inclusive approach counts a symptom if it is present without considering whether it is due to the underlying medical condition. Using the inclusive approach, a patient with Parkinson’s disease and insomnia would be counted as having insomnia as a depressive symptom if they stated that they could not fall asleep for two hours regardless of whether they said the insomnia was due to dyskinesias or guilty ruminations. The aetiological approach counts a symptom towards a diagnosis of depression only if the rater determines that it is not due to the underlying medical disorder. In the example given above the clinician would try to determine if the insomnia was due to depression or dyskinesias. Clearly this distinction can be difficult, particularly because patients, their families and clinicians tend to discount many depressive symptoms because they are felt to be a symptom of the medical illness.

However, the research in this area would support the use of the inclusive approach as more reliable in diagnosing depression in patients with co-morbid medical illnesses⁴⁵ and medical conditions such as post-stroke depression⁴⁶. The inclusive approach is more objective, whereas the aetiological approach is subject to the judgement of the clinician and is inherently less reliable. The danger in using the inclusive approach is a loss of specificity and an over-diagnosis of depression. However, the real danger in evaluating medically ill patients with depression is a loss of sensitivity and missing patients who could potentially benefit from somatic treatments. As described below, co-morbid medical illnesses can have a significant detrimental effect on long-term outcomes and mortality. The available treatments for depression are increasingly better tolerated by the elderly and the risk/benefit ratio favours a modest overtreatment of depressive syndromes in the elderly.

Certain endocrine and vitamin deficiencies, medications and medical conditions are associated with depressive symptoms. Discontinuing the offending medication, and/or correcting the endocrine or vitamin deficiency should be done prior to starting an antidepressant⁴⁷. Other medical conditions, such as Parkinson’s disease, multiple sclerosis, pancreatic cancer and stroke, are associated with high rates of co-morbid depression and the depressive episode should be treated while managing the co-morbid medical condition. Again, the clinician should not try to determine if the depression is due to the disability of the medical condition but should treat the depression if the patient meets criteria for the disorder.

Parkinson’s disease is illustrative of a neurological condition associated with high rates of depression, overlapping symptoms of depression, and the importance of recognizing and treating co-morbid depression in patients with medical disorders. Co-morbid depression occurs in about 20-30% of patients with Parkinson’s disease^48,49. There is considerable overlap of the symptoms of Parkinson’s disease and depression, including flat affect, bradyki- nesia, fatigue, agitation (in the form of psychomotor agitation or dyskinesias), insomnia and cognitive problems. Yet depression in patients with Parkinson’s disease can be accurately diagnosed using the inclusive approach and many depression psychiatric rating scales⁵⁰. Co-morbid depression is not simply a reaction to the medical illness and disability⁵¹; there is evidence of the underlying neuroanatomic degeneration secondary to Parkinson’s disease as a cause of depressive syndromes in Parkinson’s disease⁵², and the treatment of depression can lead to an improvement in the overall quality of life⁵³. The identification and treatment of Parkinson’s disease with co-morbid depression is therefore important.

Cerebrovascular disease has been shown to be associated with the development of mood symptoms. Depression is a risk factor for stroke⁵⁴ and approximately half of post-stroke depressions will meet criteria for major depression, and the other half will have minor depression⁵⁵. Robinson pioneered the early work in understanding the relationship between lesion location (i.e. subcortical in the left anterior pole) as crucial to the development of depression^56-58 and independent of the amount of physical disability caused by the stroke⁵⁹. Post-stroke depression is associated with a longer recovery time⁶⁰ and increased mortality⁶¹, and the treatment of post-stroke depression is associated with improved recovery in activities of daily living, cognition and decreased mortality⁶².

Controversy still exists whether a left-sided stroke presents with more depressive and catastrophic responses than right-sided insults, which have been described as lesions with emotional neglect, indifference and even euphoric responses^58,63. Hama et al.⁶⁴ found that the severity of affective depression was associated with left frontal lobe damage whereas apathetic depression was mostly related to basal ganglia damage. However, Robinson’s relationship of anatomic lesions to psychiatric symptoms laid the groundwork for understanding the interrelationship of depression and medical disease. The body of evidence in stroke with co-morbid depression also supports the importance of the detection and treatment of depressive syndromes in the long-term course of patients with cerebrovascular disease.

The relationship between dementia and depression is complicated. Over 50% of patients with dementing illnesses such as Alzheimer’s disease may also have depressive symptoms, with 20% meeting criteria for a major depressive episode⁶⁵. Depressive symptoms may also precede cognitive decline in community elders⁶⁶, and a significant number of individuals with depression and reversible cognitive deficits eventually progress to syndromic dementia^67,68. The biological markers of Alzheimer’s disease are found in patients with major depression, including the genotype apolipoprotein E s3/s4 (APOE4 )⁶⁹, which has been linked to Alzheimer’s disease. Additionally, depressed patients with the APOE4 genotype have more hippocampal shape abnormalities than depressed patients without APOE4⁷⁰, and individuals with late-onset depression and mild cognitive deficits have significant brain amyloid load in a pattern similar to the pattern found in Alzheimer’s disease⁷¹.