Depression in Older Adults

Depression in older adults not only causes distress and suffering but also leads to impairments in physical, mental, and social functioning. Despite being associated with excess morbidity and mortality, depression often goes undiagnosed and untreated. The startling reality is that a substantial proportion of older patients receive no treatment or inadequate treatment for their depression in primary care settings, according to expert consensus (NIH Consensus Development Panel on Depression in Late Life, 1992; Lebowitz et al., 1997). Part of the problem is that depression in older people is hard to disentangle from the many other disorders that affect older people, and its symptom profile is somewhat different from that in other adults. Depressive symptoms are far more common than full-fledged major depression. However, several depressive symptoms together represent a condition—explained below as “minor depression”—that can be as disabling as major depression (Unutzer et al., 1997a). Minor depression, despite the implications of the term, is major in its prevalence and impact. Eight to 20 percent of older adults in the community and up to 37 percent in primary care settings suffer from depressive symptoms. Treatment is successful, with response rates between 60 and 80 percent, but the response generally takes longer than that for other adults. In addition to reviewing information on prevalence and treatment, this section also discusses depression’s course, barriers to diagnosis, interactions with physical disease, consequences, cost, and etiology.

Diagnosis of Major and “Minor” Depression

The term “major depression” refers to conditions with a major depressive episode, such as major depressive disorder, bipolar disorder, and related conditions. Major depressive disorder, the most common type of major depression in adults, is characterized by one or more episodes that include the following symptoms: depressed mood, loss of interest or pleasure in activities, significant weight loss or gain, sleep disturbance, psychomotor agitation or retardation, fatigue, feelings of worthlessness, loss of concentration, and recurrent thoughts of death or suicide. (For further discussion of the diagnosis of major depressive disorder, see Chapter 4.) Major depressive disorder cannot be diagnosed if symptoms last for less than 2 months after bereavement, among other exclusionary factors (DSM-IV).

Most older patients with symptoms of depression do not meet the full criteria for major depression. The new diagnostic entity of minor depression has been proposed to characterize some of these patients. “Minor depression,” a subsyndromal form of depression, is not yet recognized as an official disorder, and DSM-IV proposes further research on it.

Minor depression is more frequent than major depression, with 8 to 20 percent of older community residents displaying symptoms (Alexopoulos, 1997; Gallo & Lebowitz, 1999). The diagnosis of minor depression is not yet standardized; the research criteria proposed in DSM-IV are the same as those for major depression, but a diagnosis would require fewer symptoms and less impairment. Minor depression, in fact, is not thought to be a single syndrome, but rather a heterogeneous group of syndromes that may signify either an early or residual form of major depression, a chronic, though mild, form of depression that does not present with a full array of symptoms at any one time, called dysthymia, or a response to an identifiable stressor (Judd et al., 1994; Pincus & Wakefield-Davis, 1997). Since depression is more difficult to assess and detect in older adults, research is needed on what clinical features might help identify older adults at increased risk for sustained depressive symptoms and suicide.

Both major and minor depression are associated with significant disability in physical, social, and role functioning (Wells et al., 1989). The degree of disability may not be as great with minor depression, but because of its higher prevalence, minor depression is associated with 51 percent more days lost from work than is major depression (Broadhead et al., 1990). Major and minor depression are associated with high health care utilization and poor quality of life (see Unutzer et al., 1997a, for a review).

Late-Onset Depression
Major or minor depression diagnosed with first onset later than age 60 has been termed late-onset depression. Late-onset depression is not a diagnosis; rather, it refers to a subset of patients with major or minor depression whose later age at first onset imparts slightly different clinical characteristics, suggesting the possibility of distinct etiology. Late-onset depression shares many clinical characteristics with early-onset depression, yet some distinguishing features exist. Patients with late-onset depression display greater apathy (Krishnan et al., 1995) and less lifetime personality dysfunction (Abrams et al., 1994). Cognitive deficits may be more prominent, with more impaired executive and memory functioning (Salloway et al., 1996) and greater medial temporal lobe abnormalities on magnetic resonance imaging, similar to those seen in dementia (Greenwald et al., 1997). Other studies, however, have shown no differences in cognition between patients with late- and early-onset depression (Holroyd & Duryee, 1997). The risk of recurrence of depression is relatively high among patients with onset of depression after the age of 60 (Reynolds, 1998).

Risk factors for late-onset depression, based on results of prospective studies, include widowhood (Bruce et al., 1990; Zisook & Shuchter, 1991; Harlow et al., 1991; Mendes de Leon et al., 1994), physical illness (Cadoret & Widmer, 1988; Harlow et al., 1991; Bachman et al., 1992), educational attainment less than high school (Wallace & O’Hara, 1992; Gallo et al., 1993), impaired functional status (Bruce & Hoff, 1994), and heavy alcohol consumption (Saunders et al., 1991).

Prevalence and Incidence
Estimates of the prevalence of major depression vary widely, depending on the definition and the procedure used for counting persons with depression (Gallo & Lebowitz, 1999). Researchers applying DSM criteria for major depression have found 1-year U.S. prevalence rates of about 5 percent or less in older people (Gurland et al., 1996). The prevalence of major depression declines with age, while depressive symptoms increase (symptoms that now might warrant classification as minor depression). Romanoski and colleagues, on the basis of psychiatric interviews of adults in the Baltimore Epidemiologic Catchment Area (ECA), showed that major depression declined with advancing age (Romanoski et al., 1992). Prevalence estimates derived from symptom scales are consistent with the clinical impression that prevalence of depressive symptoms increases with advancing age. Depressive symptoms and syndromes have been identified in 8 to 20 percent of older community residents (Alexopoulos, 1997; Gallo & Lebowitz, 1999) and 17 to 35 percent of older primary care patients (Gurland et al., 1996).

Several incidence studies based on DSM criteria reflect a similar pattern of decline in rates of major depression with advancing age (Eaton et al., 1989; Eaton et al., 1997). The 13-year followup of the participants of the Baltimore Epidemiologic Catchment Area sample revealed, however, that the distribution of the incidence of DSM-based major depression across the life span was bimodal, with a primary peak in the fourth decade and a secondary peak in the sixth decade (Eaton et al., 1997). In contrast to studies based on DSM criteria, several incidence studies report increased rates of depressive symptoms with age. A Swedish study reported that rates of depressive symptoms were highest in the older age groups and that rates of depression had increased in the interval from 1947–1957 to 1957–1972 (Hagnell et al., 1982). Incidence studies reveal an increased risk of depression among women as they age, consistent with findings based on prevalence surveys (Hagnell et al., 1982; Eaton et al., 1989; Gallo et al., 1993).

Thus, both prevalence and incidence studies that rely on DSM-based diagnosis of major depression suggest a decline with age, whereas symptom-based assessment studies show increased rates of depression among older adults, especially women. Evidence that older adults are less likely than younger persons to report feelings of dysphoria (i.e., sadness, unhappiness, or irritability) suggests that the standard criteria for depression may be more difficult to apply to older adults (Gallo et al., 1994) or that older adults are disinclined to report such feelings.

Other mood disorders, such as dysthymia, bipolar disorder, and hypomania,¹ also are present in older individuals. Little difference has been found in the prevalence of affective disorders between African Americans and whites over the age of 65 (Weissman et al., 1991). The prevalence of bipolar disorder among people aged 65 and over is reportedly less than 1 percent (Robins & Regier, 1991). Approximately 5 to 10 percent of older patients presenting with mood disorders are manic or hypomanic (Yassa et al., 1988). However, these mood disorders will not be the focus of this section of the report, as they are much less common in older adults than depression.

Barriers to Diagnosis and Treatment
The underdiagnosis and undertreatment of depression in primary care represent a serious public health problem (NIH Consensus Development Panel on Depression in Late Life, 1992). One study found that only about 11 percent of depressed patients in primary care received adequate antidepressant treatment (in terms of dose and duration of pharmacotherapy), while 34 percent received inadequate treatment and 55 percent received no treatment (Katon et al., 1992).

There are many barriers to the diagnosis of depression in late life. Some of these barriers reflect the nature of the disorder: depression occurs in a complex medical and psychosocial context. In the elderly, the signs and symptoms of major depression are frequently attributed to “normal aging,” atherosclerosis, Alzheimer’s disease, or any of a host of other age-associated afflictions. Psychosocial antecedents such as loss, combined with decrements in physical health and sensory impairment, can also divert attention from clinical depression.

Another reason for the underdiagnosis is that older patients are less likely to report symptoms of dysphoria and worthlessness, which are often considered hallmarks of the diagnosis of depression. The consequences of underdiagnosis of this subset of patients can be severe. On the basis of a followup of older adults in the Baltimore Epidemiologic Catchment Area sample, persons with depressive symptoms (e.g., sleep and appetite disturbance) without sadness (e.g., hopelessness, worthlessness, thoughts of death, wanting to die, or suicide) were at increased risk for subsequent functional impairment, cognitive impairment, psychological distress, and death over the course of the 13-year interval (Gallo et al., 1997).

Other barriers to diagnosis are patient related. Depression can and frequently does amplify physical symptoms, distracting patients’ and providers’ attention from the underlying depression; and many older patients may deny psychological symptoms of depression or refuse to accept the diagnosis because of stigma. This appears to be particularly the case with older men, who also have the highest rates of suicide in later life (Hoyert et al., 1999).

Provider-related factors also appear to play a role in underdetection of depression and suicide risk. Providers may be reluctant to inform older patients of a diagnosis of depression, owing to uncertainty about diagnosis, reluctance to stigmatize, uncertainty about optimal treatment, concern about medication interactions or lack of access to psychiatric care, and continuing concern about the effectiveness and cost-effectiveness of treatment intervention (NIH Consensus Development Panel on Depression in Late Life, 1992; Unutzer et al., 1997a).

Societal stereotypes about aging also can hamper efforts to identify and diagnose depression in late life. Many people believe that depression in response to the loss of a loved one, increased physical limitations, or changing societal role is an inevitable part of aging. Even physicians appear to hold such stereotyped views. Three-quarters of physicians in one study thought that depression “was understandable” in older persons (Gallo et al., in press), consistent with other studies (Bartels et al., 1997). Suicidal thoughts are sometimes considered a normal facet of old age. These mistaken beliefs can lead to underreporting of symptoms by patients and lack of effort on the part of family members to seek care for patients.

Finally, the health care system itself is increasingly restricting the time spent in patient care, forcing mental health concerns to compete with comorbid general medical conditions. Primary care physicians often report feeling too pressured for time to investigate depression in older people (Glasser & Gravdal, 1997). Given the inseparability of mental and general health in later life particularly, this trend is worrisome.

Course
Across the life span, the course of depression is marked by recurrent episodes of depression followed by periods of remission. In late life, the course of depression tends to be more chronic than that in younger adults (Alexopoulos & Chester, 1992; Callahan et al., 1994; Cole & Bellavance, 1997). This means that recurrences extend for longer duration, while intervals of remission are shorter. It also means that cycles of recurrence and remission persist over a longer period of time. Patients’ response to treatment is highly variable, and the determinants of treatment response and its temporal profile are the subjects of intense research (Reynolds & Kupfer, 1999). A slower, less consistent response, which suggests a higher probability of relapse, is related to older age, presence of acute and chronic stressors, lower levels of perceived social support, higher levels of pretreatment anxiety, and greater biologic dysregulation as reflected in higher levels of rapid eye movement sleep (Dew et al., 1997). The temporal profile of the initial treatment response also may provide important clues about which patients are likely to fare well on maintenance treatment and which ones are likely to have a brittle treatment response and stormy long-term course.

A recent update of the NIH Consensus Development Conference on the Diagnosis and Treatment of Late-Life Depression emphasized the need for more data to guide long-term treatment planning, especially in patients 70 years and older with major depression (Lebowitz et al., 1997). Little is currently known about differences, if any, in speed and rate of remission, relapse, recovery, and recurrence in patients aged 60 to 69 and those aged 70 and above. In a study at the University of Pittsburgh, two groups of patients (ages 60 to 69 and 70+) showed comparable times to remission and recovery, as well as similar absolute rates of remission during acute therapy, relapse during continuation therapy, and recovery. However, patients aged 70 and older experienced a significantly higher rate of recurrence during the first year of maintenance therapy (Reynolds, 1998). Thus, the course of depression and its interaction with treatment are influenced by age. This highlights the importance of research targeted at older age groups instead of reliance on extrapolations from younger patients.

Interactions With Somatic Illness
Late-life mental disorders are often detected in association with somatic illness (Reynolds & Kupfer, 1999). The prevalence of clinically significant depression in later life is estimated to be highest—approximately 25 percent—among those with chronic illness, especially with ischemic heart disease, stroke, cancer, chronic lung disease, arthritis, Alzheimer’s disease, and Parkinson’s disease (Borson et al., 1986; Blazer, 1989; Oxman et al., 1990; Callahan et al., 1994; Beekman et al., 1995; Borson, 1995).

The relationship between somatic illness and mental disorders is likely to be reciprocal, but the mechanisms are far from understood. Biological and psychological factors are thought to play a role (Unutzer et al., 1997a). The nature and course of late-life depression can be greatly affected by the coexistence of one or more other medical conditions.

Insomnia and sleep disturbance play a large role in the clinical presentation of older depressed patients. Sleep complaints over time in community-residing older people have been found to vary with the intensity of depressive symptoms (Rodin et al., 1988). Sleep disturbances in older men and women have also been recently linked to poor health, depression, angina, limitations in activities of daily living, and chronic use of benzodiazepines (Newman et al., 1997). Furthermore, persistent or residual sleep disturbance in older patients with prior depressive episodes predicts a less successful maintenance response to pharmacotherapy (Buysse et al., 1996). The prevalence of chronic, primary insomnia in older adults is estimated at 5 to 10 percent (Ohayon et al., 1996). Relatively little is known about the etiology or pathophysiology of chronic primary insomnia and why it constitutes a risk factor for depression in older adults. An important issue for further research is whether effective treatment for chronic insomnia could prevent the subsequent development of clinical depression in midlife and later.

Consequences of Depression

The most serious consequence of depression in later life—especially untreated or inadequately treated depression—is increased mortality from either suicide or somatic illness. Older persons (65 years and above) have the highest suicide rates of any age group. The suicide rate for individuals age 85 and older is the highest, at about 21 suicides per 100,000, a rate almost twice the overall national rate of 10.6 per 100,000 (CDC, 1999). The high suicide rate among older people is largely accounted for by white men, whose suicide rate at age 85 and above is about 65 per 100,000 (CDC, 1999). Trends from 1980 to 1992 reveal that suicide rates are increasing among more recent cohorts of older persons (Kachur et al., 1995). Since national statistics are unlikely to include more veiled forms of suicide, such as nursing home residents who stop eating, estimates are probably conservative.

Suicide in older adults is most associated with late-onset depression: among patients 75 years of age and older, 60 to 75 percent of suicides have diagnosable depression (Conwell, 1996). Using a “psychological autopsy,” Conwell and coworkers investigated all suicides within a geographical region and found that with increasing age, depression was more likely to be unaccompanied by other conditions such as substance abuse (Conwell et al., 1996). While thoughts of death may be developmentally expected in older adults, suicidal thoughts are not. From a stratified sample of primary care patients over age 60, Callahan and colleagues estimated the prevalence of specific suicidal thoughts at 0.7 to 1.2 percent (Callahan et al., 1996b). Unfortunately, no demographic or clinical variables distinguished depressed suicidal patients from depressed nonsuicidal patients (Callahan et al., 1996b).

Swedish researchers found much higher rates of suicidal ideation after interviewing adults aged 85 years and older. They found a 1-month prevalence of any suicidal feelings in 9.6 percent of men and 18.7 percent of women (Skoog et al., 1996). Suicidal feelings were strongly associated with depression. For example, 6.2 percent of the participants who did not meet criteria for depression or anxiety reported suicidal thoughts, while almost 50 percent of those meeting criteria for depression reported such thoughts. The higher prevalence of suicidal feelings in this study, compared with that cited earlier, is likely due to the older age of subjects and to methodological differences.

Studies of older persons who have committed suicide have revealed that older adults had seen their physician within a short interval of completing suicide, yet few were receiving mental health treatment. Caine and coworkers studied the records of 97 adults aged 50 years and older who completed suicide (Caine et al., 1996). Of this group, 51 had seen their primary care physician within 1 month of the suicide. Forty-five had psychiatric symptoms. Yet in only 29 of the 45 individuals were symptoms recognized, in only 19 was treatment offered, and in only 2 of these 19 cases was the treatment rendered considered adequate. Treatment was deemed inadequate if an incorrect medicine (such as a benzodiazepine for severe major depression) or inadequate dose was prescribed. This line of research highlights important opportunities for suicide prevention.

Depression also can lead to increased mortality from other diseases, such as heart disease and possibly cancer. How depression exerts these effects is not yet understood. In nursing home patients, major depression increases the likelihood of mortality by 59 percent, independent of physical health measures (Rovner, 1993). In the case of myocardial infarction, depression elevates mortality risk fivefold (Frasure-Smith et al., 1993, 1995). Depression also has been linked to the onset of cancer, but results have been inconsistent. Yet a new epidemiological study, considered the most compelling to date, finds that chronic depression (lasting an average of about 4 years) raises the risk of cancer by 88 percent in older people (Penninx et al., 1998). Thus, increased understanding of depression in older people may be, literally, a matter of life and death.

Cost

The high prevalence of depressive syndromes and symptoms in older adults exacts a large economic toll. Depression as a whole for all age groups is one of the most costly disorders in the United States (Hirschfeld et al., 1997). The direct and indirect costs of depression have been estimated at $43 billion each year, not including pain and suffering and diminished quality of life (Finkelstein et al., 1996). Late-life depression is particularly costly because of the excess disability that it causes and its deleterious interaction with physical health. Older primary care patients with depression visit the doctor and emergency room more often, use more medication, incur higher outpatient charges, and stay longer at the hospital (Callahan et al., 1994; Cooper-Patrick et al., 1994; Callahan & Wolinsky, 1995; Unutzer et al., 1997b).

Etiology of Late-Onset Depression

Despite major advances, the etiology of depression occurring at any age is not fully understood, although biological and psychosocial factors clearly play an important and interactive role.

With respect to late-onset depression, several risk factors have been identified. Persistent insomnia, occurring in 5 to 10 percent of older adults, is a known risk factor for the subsequent onset of new cases of major depression both in middle-aged and older persons (Ford & Kamerow, 1989). Grief following the death of a loved one also is an important risk factor for both major and minor depression. At least 10 to 20 percent of widows and widowers develop clinically significant depression during the first year of bereavement. Without treatment, such depressions tend to persist, becoming chronic and leading to further disability and impairments in general health (Zisook & Shuchter, 1993). A final pathway to late-onset depression, suggested by computed tomography and magnetic resonance imaging studies, may involve structural, neuroanatomic factors. Enlarged lateral ventricles, cortical atrophy, increased white matter hyperintensities, decreased caudate size, and vascular lesions in the caudate nucleus appear to be especially prominent in late-onset depression associated with vascular risk factors (Ohayon et al., 1996; Baldwin & Tomenson, 1995). These findings have generated the vascular hypothesis of late-onset depression; namely, that even in the absence of a clear stroke, disorders that cause vascular damage, such as hypertension, coronary artery disease, and diabetes mellitus, may induce cerebral pathology that constitutes a vulnerability for depression (Alexopoulos et al., 1997; Steffens & Krishnan, 1998).

Treatment of Depression in Older Adults

A broad array of effective treatments, both pharmacological and psychosocial, exists for depression. Despite the pervasiveness of depression and the existence of effective treatments, a substantial fraction of patients receive either no treatment or inadequate treatment, as described earlier. Some of the barriers relate to underdiagnosis, while others relate to treatment where there are patient, provider, and clinical barriers (for more details see Unutzer et al., 1996).

Pharmacological Treatment
There is consistent evidence that older patients, even the very old, respond to antidepressant medication (Reynolds & Kupfer, 1999). About 60 to 80 percent of older patients respond to treatment, while the placebo response rate is about 30 to 40 percent (Schneider, 1996). These rates are comparable to those in other adults (see Chapter 4). Treatment response is typically defined by a significant reduction—usually 50 percent or greater—in symptom severity. Yet because patients 75 years old and older typically have higher prevalence of medical comorbidity, both they and their physicians are often reluctant to add another medication to an already complex regimen in a frail individual. However, newer antidepressants are less frequently associated with factors contraindicating their use. Moreover, because the very old are also at high risk for adverse medical outcomes of depression and for suicide, treatment may be favored. Despite the availability of effective treatments, a minority of patients properly diagnosed with depression receive adequate dosage and duration of pharmacotherapy, as noted earlier.

In general, pharmacological treatment of depression in older people is similar to that in other adults, but the selection of medications is more complex because of side effects and interactions with other medications for concomitant somatic disorders. Treatment of minor depression is generally the same as treatment for major depression, but there is not a large body of evidence to support this practice. Studies are under way to identify effective pharmacological treatments for minor depression (Lebowitz et al., 1997).

The following paragraphs describe the major classes of medications for treatment of depression in older adults. They focus on side effects and other concerns that distinguish the treatment of depression in older adults from that in younger ones.

Tricyclic Antidepressants
Tricyclic antidepressants (TCAs) have been widely used to treat depressed patients of all ages. Alexopoulos and Salzman (1998) reviewed studies of TCAs in older depressed patients and concluded that these compounds are similar in efficacy across the age spectrum, but the side effect profiles differ considerably. Widespread use of the TCAs in older adults is limited by adverse reactions. While anticholinergic effects such as dry mouth, urinary retention, and constipation can be annoying in younger adults, they can lead to severe problems in older adults. For example, constipation can lead to impaction, and dry mouth can prevent the wearing of dentures. The anticholinergic effects of the TCAs may also cause tachycardia or arrhythmias and can further compromise preexisting cardiac disease (Roose et al., 1987; Glassman et al., 1993). Central anticholinergic effects may result in acute confusional states or memory problems in the depressed older adult (Branconnier et al., 1982). Orthostatic hypotension, which may lead to falls and hip fractures, is also a concern when the TCAs are administered. Nevertheless, TCAs are still frequently used in older adults.

Selective Serotonin Reuptake Inhibitors and Other Newer Antidepressants
Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, and sertraline, whose use is increasing across age groups, may be especially useful in the treatment of late-life depression, because these agents are reported to have fewer anticholinergic and cardiovascular side effects than the TCAs. The more commonly observed side effects with SSRIs include sexual dysfunction and gastrointestinal effects such as nausea, vomiting, and loose stools. Treatment with the SSRIs may also produce insomnia, anxiety, and restlessness. The few studies that have examined the efficacy of these compounds in older adults have shown efficacy similar to the TCAs and fewer side effects (see Small & Salzman, 1998, for a review). While the relative efficacy of SSRIs and TCAs is still debated, SSRIs are easier to prescribe because of simpler dosing patterns and more manageable side effects.

One concern when prescribing the SSRIs in older adults is the potential for drug-drug interactions. This is of clinical importance since older adults commonly receive a large number of medications. The SSRIs vary in their inhibition of the cytochrome p450 family of isoenzymes. Knowledge of these patterns of inhibition in the SSRIs and other medications commonly used in older adults (such as other psychoactive compounds, calcium channel blockers, or warfarin) can help to avoid or minimize interactions. Other newer non-SSRI antidepressants (venlafaxine, bupropion, trazodone, and nefazodone) are often suggested for treating later life depression because their side effects are better tolerated by older adults.

Some compounds that are useful in other individuals may be less useful for treatment of older patients. For example, despite evidence of the efficacy of monamine oxidase inhibitors (see Alexopoulos & Salzman, 1998, for a review), clinical use is often restricted to patients who are refractory to other antidepressant drugs. This is due to potentially life-threatening pharmacodynamic interactions with sympathomimetic drugs or tyramine-containing foods and beverages. The sympathomimetic amines (e.g., phenylpropanolamine and pseudoephedrine) may be present in over-the-counter decongestant products that older patients are prone to self-administer. An additional concern is the risk of orthostatic hypotension, which occurs even at therapeutic doses (Alexopoulos & Salzman, 1998). In addition, bupropion has been shown in older patients to be as effective as TCAs (Branconnier et al., 1983; Kane et al., 1983). Although generally well tolerated, its use requires added caution because of an increased risk of seizures and thus should be avoided in patients with seizure disorder or focal central nervous system disease. Its advantages include a relatively low incidence of cardiovascular complications and a lack of confusion.

Multimodal Therapy
Combining pharmacotherapy with psychosocial interventions also appears to be effective in older depressed patients. A high response rate of about 80 percent was found for acute and continuation treatment with combined nortriptyline and interpersonal psychotherapy. The response rate was similar between so-called “young old” patients (primarily in their 60s and early 70s) and patients in their 30s and 40s (Reynolds et al., 1996). Yet older patients showed a somewhat longer time to remission than did other patients (about 2 weeks longer) and twice the rate of relapse during continuation treatment (about 15 percent versus 7 percent). However, because the trial was not controlled, it is not known whether multimodal treatment was more effective than either pharmacological or psychosocial treatment alone. Treatment resistance—defined by the lack of recovery in spite of combined treatment with nortriptyline and interpersonal psychotherapy—was seen in about 18 percent of older patients with recurrent major depression (nonpsychotic unipolar depression) (Little et al., 1998). Nortriptyline and interpersonal psychotherapy (IPT) have been shown to be effective maintenance treatments for late-life depression. After 3 years of comparing various treatments, the percentage of older adults who did not experience recurrence were 57 percent of older adults receiving nortriptyline, 36 percent receiving IPT, and 80 percent of those receiving nortriptyline plus IPT. Those receiving a placebo and routine clinical visits had a 90 percent recurrence rate (Reynolds et al., 1999).

Course of Treatment
Although 60 to 80 percent of older patients with moderate to severe unipolar² depression can be expected to respond well to antidepressant treatment (especially combined treatment with medication and psychotherapy), the clinical response to antidepressant treatment in later life follows a variable course, with a median time to remission of 12 weeks (J. L. Cummings & D. J. Kupfer, personal communication, 1999). Thus, treatment response takes 1 month or more longer than that for other adults, for whom treatment response takes an average of 6 to 8 weeks (see Chapter 4). In addition to highly variable trajectories to recovery, reliable prediction of response status (recovery/nonrecovery) is generally not possible in older adults before 4 to 5 weeks of treatment. The delayed onset of antidepressant activity in older adults leads to unique problems. Suffering and disability are prolonged, which often reduces compliance and may increase risk for suicide. The development of strategies to accelerate treatment response and to improve the early identification of nonresponders would be an important advance (Reynolds & Kupfer, 1999).

Data from naturalistic studies have identified several predictors of relapse and recurrence in late-life depression, including a history of frequent episodes, first episode after age 60, concurrent somatic illness, especially a history of myocardial infarction or vascular disease, high pretreatment severity of depression and anxiety, and cognitive impairment, especially frontal lobe dysfunction. These factors appear to interact with low treatment intensity—that is, at dosage and duration below recommended levels—in determining more severe courses of illness. Despite the evidence that high treatment intensity is effective in preventing relapse and recurrence (Reynolds et al., 1995), naturalistic studies have shown that intensity of treatment prescribed by psychiatrists begins to decline within 16 weeks of entry and approximately 10 weeks prior to recovery (Alexopoulos et al., 1996). Residual symptoms of excessive anxiety and worrying predict early recurrence after tapering continuation treatment in older depressed patients (Meyers, 1996).

Although progress has been made in identifying effective pharmacological and combined treatments for late-life depression, there is a need for more outcome studies with newer antidepressants. In addition, studies examining effectiveness in real-world settings—rather than in clinical trials conducted in academic clinical sites—are particularly crucial in the older population because of medical comorbidity and provision of care in primary, rather than specialty, care.

Electroconvulsive Therapy
Electroconvulsive therapy (ECT) is regarded as an effective intervention for some forms of treatment-resistant depression across the life cycle (NIH & NIMH Consensus Conference, 1985; Depression Guideline Panel, 1993). It may offer a particularly attractive benefit:risk ratio in older persons with depression (NIH Consensus Development Panel on Depression in Late Life, 1992; Sackeim, 1994). Chapter 4 reviews research on ECT and considers risk-benefit issues and controversy surrounding them. As described there, ECT entails the electrical induction of seizures in the brain, administered during a series of 6 to 12 treatment sessions on an inpatient or outpatient basis. Practice guidelines recommend that ECT should be reserved for severe cases of depression, particularly with active suicidal risk or psychosis; patients unresponsive to medications; and those who cannot tolerate medications (NIH & NIMH Consensus Conference, 1985; Depression Guideline Panel, 1993). For those patients, the response rate to ECT is on the order of 50 to 70 percent, and there is no evidence that ECT is any less effective in older individuals than younger ones (Sackeim, 1994; Weiner & Krystal, 1994). ECT is advantageous for older people with depression because of the special problems they encounter with medications, including sensitivity to anticholinergic toxicity, cardiac conduction slowing, and hypotension (see above). Although the newer antidepressants offer a more favorable side-effect profile than do the older tricyclics, their efficacy in melancholic depression, for which ECT is particularly helpful (Rudorfer et al., 1997), is not yet firmly established. Moreover, as noted earlier, older adults respond more slowly than younger ones to antidepressant medications, rendering the faster onset of action of ECT another advantage in the older patient (Markowitz et al., 1987). Immobility and reduced food and fluid intake in the older person with depression may pose a greater imminent physical health risk than would typically be the case in a younger patient, again strengthening the case for considering ECT early in the treatment hierarchy (Sackeim, 1994).

Although the clinical effectiveness of ECT is documented and acknowledged, the treatment often is associated with troubling side effects, principally a brief period of confusion following administration and a temporary period of memory disruption (Rudorfer et al., 1997). As described in Chapter 4, there may also be longer term memory losses for the time period surrounding the use of ECT. Although the exception rather than the rule, persistent memory loss following ECT is reported. Its actual incidence is unknown. There are no absolute medical contraindications to ECT. However, a recent history of myocardial infarct, irregular cardiac rhythm, or other heart conditions suggests the need for caution due to the risks of general anesthesia and the brief rise in heart rate, blood pressure, and load on the heart that accompany ECT administration. On the other hand, the safety of ECT is enhanced by the time-limited nature of treatment sessions, which enables this intervention to be administered under controlled conditions, for example, with a cardiologist or other specialist in attendance. Following completion of a course of ECT, maintenance treatment, typically with antidepressant or mood-stabilizing medication or less frequent maintenance ECT, in most cases is required to prevent relapse (Rudorfer et al., 1997).

Psychosocial Treatment of Depression
Most research to date on psychosocial treatment of mental disorders has concentrated on depression. These studies suggest that several forms of psychotherapy are effective for the treatment of late-life depression, including cognitive-behavioral therapy, interpersonal psychotherapy, problem-solving therapy, brief psychodynamic psychotherapy, and reminiscence therapy, an intervention developed specifically for older adults on the premise that reflection upon positive and negative past life experiences enables the individual to overcome feelings of depression and despair (Butler, 1974; Butler et al., 1991). Group and individual formats have been used successfully.

A meta-analysis of 17 studies of cognitive, behavioral, brief psychodynamic, interpersonal, reminiscence, and eclectic therapies for late-life depression found treatment to be more effective than no treatment or placebo (Scogin & McElreath, 1994). The following paragraphs spotlight some of the key studies incorporated into this meta-analysis and provide evidence from newer studies.

Cognitive-behavioral therapy is designed to modify thought patterns, improve skills, and alter the emotional states that contribute to the onset, or perpetuation, of mental disorders. In a 2-year followup study of cognitive-behavioral therapy, 70 percent of all patients studied no longer met criteria for major depression and maintained treatment gains (Gallagher-Thompson et al., 1990). In another trial, group cognitive therapy was found to be effective. Older patients with major depression partially randomized to receive group cognitive therapy with alprazolam (a benzodiazepine) or group cognitive therapy with placebo had more improvement in depressed mood and sleep efficiency than patients who received alprazolam alone or placebo alone (Beutler et al., 1987). Cognitive-behavioral therapy also has been demonstrated to be effective in other late-life disorders, including anxiety disorders (Stanley et al., 1996; Beck & Stanley, 1997). Cognitive-behavioral therapy’s effectiveness for mood symptoms in Alzheimer’s disease is discussed in the section on psychosocial treatments of Alzheimer’s disease.

Problem-solving therapy postulates that deficiencies in social problem-solving skills enhance the risk for depression and other psychiatric symptoms. Through improving problem-solving skills, older patients are given the tools to enable them to cope with stressors and thereby experience fewer symptoms of psychopathology (Hawton & Kirk, 1989). Problem-solving therapy has been found effective in the treatment of depression of older patients. For example, problem-solving therapy was found to significantly reduce symptoms of major depression, leading to the greatest improvement in a randomized controlled study comparing problem-solving therapy, reminiscence therapy, and placement on a waiting list for treatment (Arean et al., 1993). In a randomized study of depressed younger primary care patients, six sessions of problem-solving therapy were as effective as amitriptyline, with about 50 to 60 percent of patients in each group recovering (Mynors-Wallis et al., 1995).

Interpersonal psychotherapy was initially designed as a time-limited treatment for midlife depression. It focuses on grief, role disputes, role transitions, and interpersonal deficits (Klerman et al., 1984). This form of treatment may be especially meaningful for older patients given the multiple losses, role changes, social isolation, and helplessness associated with late-life depression. Controlled trials suggest that interpersonal psychotherapy alone, or in combination with pharmacotherapy, is effective in all phases of treatment for late-life major depression. Interpersonal psychotherapy was as effective as the antidepressant nortriptyline in depressed older outpatients, and both were superior to placebo (Sloane et al., 1985; Reynolds et al., 1992; Schneider, 1995). In an open trial, a treatment protocol combining interpersonal psychotherapy with nortriptyline and psychoeducational support groups led to minimal attrition and high remission rates (approximately 80 percent) in older patients with recurrent major depression (Reynolds et al., 1992, 1994). Finally, interpersonal psychotherapy also is effective in the treatment of depression following bereavement (Pasternak et al., 1997).

Brief psychodynamic therapy, typically of 3 to 4 months’ duration, also is successful in older depressed patients. Brief psychodynamic therapy is distinguished from traditional psychodynamic therapy primarily by duration of treatment. The goals of brief psychodynamic therapy vary according to patients’ medical health and function. In disabled older people, the purpose of psychodynamic psychotherapy is to facilitate mourning of lost capacities, promote acceptance of physical limitations, address fears of dependency, and promote resolution of interpersonal difficulties with family members (Lazarus & Sadavoy, 1996). In older patients who are not disabled, psychodynamic psychotherapy deals with the resolution of interpersonal conflicts, adaptation to loss and stress, and the reconciliation of personal accomplishments and disappointments (Pollock, 1987). Brief psychodynamic therapy has been found to be as effective as cognitive-behavioral therapy in reducing symptoms of late-life major depression. An early study found brief psychodynamic therapy to yield higher relapse and recurrence rates than did cognitive and behavioral therapy (Gallagher & Thompson, 1982). However, with a greater number of patients, brief psychodynamic therapy was determined to be as effective as cognitive and behavioral therapy (and superior to being on a waiting list) in preventing recurrences of major depression up to 2 years after treatment (Gallagher-Thompson et al., 1990).

² Unipolar depression refers to the depression in patients with major depressive disorders but not to the depression in patients with bipolar disorders.