Recognition and Management of Late Life Mood DisordersJames M. Ellison
Gary L. Gottlieb
Aging is not inevitably accompanied by a disturbance of mood, yet depressive symptoms among elderly women and men are common and disabling. Most depressed elderly patients who seek treatment do so in a primary care setting, where detection is often poor and treatment is frequently inadequate. Individuals confined in long-term care facilities rely on primary care clinicians for treatment or referral to a mental health specialist, with the result that many go untreated. Elderly sufferers of depression or of mania, which is less prevalent, consume disproportionately large amounts of medical health care resources (16,129) and die prematurely of medical causes (16,103) or suicide (27). For those who survive, the functional impairment associated with a mood disorder can exhaust caregivers and tip the balance from independent living toward an early need for institutional care. Improved recognition and management of late life mood disorders can alleviate suffering, reduce functional impairment, decrease mortality, and spare caregivers a substantial burden. This chapter reviews the syndromes most frequently seen among the elderly, focusing on their clinical and epidemiologic characteristics and summarizing current approaches to management.
DIAGNOSIS OF LATE LIFE DEPRESSION
Depressive symptoms fall into several characteristic syndromes. The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM) (7) defines major depressive episodes as requiring five or more core symptoms present during a 2-week period, not attributable to the use of a substance or a medical illness. One of the symptoms must be depressed mood or loss of interest or pleasure, whereas others can be drawn from the following list: weight loss, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, worthlessness or guilt, diminished concentration, and recurrent thoughts of death or suicide. Psychotic features such as delusions, hallucinations, or severe disturbance of motor function (stupor or agitation) may also be present. Dysthymic disorder, a chronic but less florid depressive state, is diagnosed when depressed mood has been accompanied by two or more of the depressive symptoms listed earlier for an extended period of time (present more days than not for at least 2 years) (7). The presence of fewer, milder, or briefer symptoms is termed minor depression or subsyndromal depression.
In assessing elderly patients, the diagnosis of depression is made more challenging by muted or obscure expression of signs and symptoms. In contrast with younger patients, the current cohort of depressed elderly often places less emphasis on a sad or depressed mood; instead, anger, irritability, anxiety, cognitive difficulties, or somatic concerns may be the focus of attention. Somatic symptoms associated with known medical illnesses affect most of the depressed elderly. Medically explainable symptoms are often magnified by the presence of depression and confounded by the presence of additional symptoms that are not medically explainable. Although psychological symptoms of depression are present in most depressed elderly (113), their detection requires attentive inquiry. When cognitive impairment is prominent, mood symptoms are even less likely to be reported. Deterioration of function and interpersonal interactions may then provide the strongest clue to the presence of a mood disorder.
Among depressed elderly patients who present with prominent cognitive symptoms, the non-DSM diagnosis of dementia syndrome of depression (DSD) may be appropriate. Formerly termed pseudodementia because of the partial cognitive improvement associated with successful resolution of other depressive symptoms, this syndrome can lead to an erroneous diagnosis of primary dementia, resulting in a missed opportunity to treat depression (52). Ample follow-up evidence now demonstrates that DSD, although responsive to antidepressant treatment in the short run, often presages the later appearance of a primary dementia (45,91). Features that help to differentiate DSD from a primary dementia include the more likely presence of an autonomous mood disorder, more rapid progression of symptoms, greater patient awareness of and complaint regarding cognitive
symptoms, and previous history of a mood disorder. In addition to these features, on neuropsychological assessment, the patient may show poorer effort in attempting to perform tasks, greater intactness of recognition memory, better performance with prompting, and more variable performance on similarly difficult tasks (45).
symptoms, and previous history of a mood disorder. In addition to these features, on neuropsychological assessment, the patient may show poorer effort in attempting to perform tasks, greater intactness of recognition memory, better performance with prompting, and more variable performance on similarly difficult tasks (45).
DEMOGRAPHICS AND RISK FACTORS
Many clinicians and patients assume that mood disorders are more prevalent among the elderly than among young adults, given the recognized losses and stresses associated with aging, but epidemiologic data consistently contradict such an assertion. With the possible exception of the oldest old (144), evidence suggests that major depressive disorder is no more prevalent among the elderly than among younger adults (17). Data from the Epidemiologic Catchment Area studies estimated a 1-year prevalence among community-dwelling elderly of 2.7% for major depression (135). By contrast, subsyndromal depression affects a large number (8% to 15%) of community-dwelling elderly persons (17).
In contrast to the general population of community-dwelling elderly, specific subgroups have been shown to suffer a higher prevalence of depression. Borson et al. (19) detected major depression in 10% of an elderly population with chronic medical illnesses. In a primary care clinic setting, a prevalence of 5.6% was measured for major depression among the elderly patients, and an additional 7.9% had probable or masked depression (15). In long-term care facilities, the only mental disorder more common among the elderly than depression is dementia. The prevalence of major depression in nursing homes is estimated to be between 6% and 25%, with 30% to 50% of nursing home residents suffering subsyndromal symptoms (49). The annual rate of new cases of major depression in nursing homes is as high as 9.4%, and each year, an additional 7.4% develop new minor depressions (86).
Among the risk factors linked to late life depression, a higher prevalence is associated with female gender (17); lower levels of educational attainment; a history of childhood poverty, sexual assault, or parental separation or divorce; lower income and occupational attainments; widowhood or other unmarried states; lack of integration into a supportive social network; chronic financial or medical stresses; acute provoking events (34); and a history of heavy alcohol consumption (109). Neither race nor ethnicity appears to be an important risk factor for late life depression (76).
Depression and aging are themselves risk factors for suicide, an all too frequent complication of late life depression. The rate of completed suicide increases significantly with advancing age, notably among white men (70). Among the elderly, depression is strongly correlated with the risk of either suicide attempts (63,83) or completion (14,26,27). The increased prevalence of depression in various medical illnesses (e.g., multiple sclerosis, epilepsy, Huntington’s disease, traumatic spinal lesions, cranial trauma, peptic ulcer disease, rheumatoid arthritis, cardiopulmonary diseases, renal disease requiring chronic hemodialysis, and chronic pain) may contribute to the increased suicide risk among patients with these illnesses (64).
DETECTION
Studies of service utilization indicate that the elderly with mood disorders are seriously undertreated. Most of the mentally ill elderly receive no services specifically for their psychiatric diagnoses. A recently published study of elderly patients treated in four primary care health maintenance organization (HMO) clinics, for example, found that only 7% of the depressed patients received treatment for depression in 1993, and only 11% to 22% of these patients saw a psychiatrist (130). In long-term care facilities, undertreatment is particularly common. As recently as 1985, the National Nursing Home Survey determined that <10% of the institutionalized elderly received services for their psychiatric diagnoses (37). Underrecognition and undertreatment are perpetuated by both provider and patient factors.
Primary care clinicians deliver most of the psychiatric care received by elderly adults. Although nearly 85% of older adults visit a primary care physician at least once a year, those with mood disorders frequently elude detection. Primary care clinicians may lack the time to thoroughly evaluate mood-related symptoms or the training and interest required for successful diagnosis and treatment. Psychotropic medications are frequently prescribed in primary care, but many of these medications are sedatives and hypnotics, rather than antidepressants (22). Unutzer et al. (128) raised the possibility that elderly patients receive different care from that provided to younger adults. They found that depressed patients older than 60 years of age receiving care from an HMO were less likely than younger depressed adults to receive adequate antidepressant doses within the first 90 days of treatment. The elderly patients were also less likely to have more than two primary care visits for depression within the first 12 weeks after a new antidepressant was prescribed or specialty mental health care within the first 6 months after the antidepressant prescription. Historically, the underprescribing of psychotherapy was highlighted by the observation that most older adults treated for a psychiatric diagnosis in primary care received only psychotropic drugs (22).
In addition to these provider factors, some patient factors interfere with effective treatment of depression in this population. Elderly patients may fail to recognize in themselves the symptoms of a depression. Shame may prevent them from divulging complaints perceived as stigmatizing. When psychiatric referral is offered, refusal appears to be common (132). The high cost of medications, despite some improvement in insurance coverage resulting from initiation of Medicare Part D, provides another powerful disincentive for accepting treatment. Even when treatment is begun, adherence to a treatment regimen is often limited. One to two thirds of the elderly do not comply or only partially comply with a prescribed medication regimen (124).
Detection of depression in the elderly can be facilitated by use of screening tools that are self-administered or rely on clinician assessments. Among the self-administered tools, the Beck Depression Inventory is validated in elderly patients. The clinician-administered Hamilton Depression Scale (HAM-D or HRSD) relies heavily on somatic symptoms, weakening its specificity in medically ill elderly patients. The Geriatric Depression Scale (GDS) is brief, easily administered, and focuses on depressive affects and cognitions. The Cornell Scale for Depression in Dementia (CSDD), which focuses on depressive behaviors, is suitable for rating of depressed patients with dementia but requires more time to administer because interviews with both the patient and the caregiver are required (2,10).
Depression must be differentiated from medical illnesses, especially those characterized by fatigue or apathy; from the effects of sedating or mood-altering medications and substances; and from other behavioral disturbances, including bereavement, anxiety disorders, or psychotic disorders. Many medical causes of depression can be detected by a limited evaluation. A minimal workup for depression in an elderly patient must include a comprehensive history, which may need to be supplemented or validated by another informant; review of relevant records and prior treatments; and a physical examination. A mental status examination with screening of cognitive functions [e.g., with the Mini-Mental State Examination (MMSE)] is also suggested. Research support has not established the optimal battery of laboratory tests for detection of medical conditions presenting with depressive symptoms, but the majority of relevant disorders are screened for with a panel that includes complete blood count, erythrocyte sedimentation rate, electrolytes, calcium, glucose, thyroid-stimulating hormone, renal and liver functions, and vitamin B12 and folate. An electrocardiogram is required before prescribing a tricyclic antidepressant to an older adult and establishes a useful baseline measure even for treatment with agents of lesser potential cardiotoxicity.
An imaging study, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), or positron emission tomography (PET), is of greatest diagnostic and prognostic value when cognitive symptoms accompany depressive symptoms. In many cases of depression in later life, an MRI will reveal subcortical white matter hyperintensities on fluid-attenuated inversion recovery (FLAIR) or T2-weighted images. Although these findings are not specific for depression, their presence in depressed individuals is associated with older age, later age at onset, and less frequent family history of mental illness (59). Various terms have evolved to describe late life depression with corticostriatal dysfunction manifested as executive dysfunction and often accompanied by greater risk of relapse, recurrence, and residual depressive symptoms (1). Vascular depression (5) and subcortical ischemic depression (60) focus on pathophysiology and etiology, whereas the clinical manifestations of depression with frontolimbic and frontostriatal dysfunction are alluded to in the syndromal designation of “depression-executive dysfunction syndrome” (3,4), a condition that can arise from vascular or nonvascular pathologies.
TREATMENT
PSYCHOTHERAPY
Although often neglected in the treatment of late life depression, several psychotherapeutic approaches have been shown to be effective treatment options for cognitively intact patients with mild to moderately severe nonpsychotic depression. Psychotherapy can be provided with or without antidepressant medication. A meta-analysis of studies found psychotherapeutic treatment to be more effective than placebo or no treatment (111). Interpersonal therapy (IPT), which was developed as a time-limited intervention for midlife depression, has been useful in treating older patients as well because it focuses on highly relevant issues including grief, loss, and role transitions (137). Cognitive-behavior therapy (CBT) provides another brief and effective approach and is aimed at helping patients identify and correct distorted thoughts that perpetuate depression while introducing more pleasurable activities into their lives (122). Psychodynamic group psychotherapy approaches have been evaluated in the elderly in comparison with cognitive behavioral approaches and found to be of similar efficacy (115), although a need exists for further studies to clarify the relative advantages of these different approaches. Other types of psychotherapy reported to be helpful have included reminiscence/life review, psychoeducation, and relaxation-meditation.
Individuals who are intolerant of medication and electroconvulsive therapy (ECT) or who prefer a psychosocial approach to treatment can be referred to a mental health specialist for a trial of psychotherapy in individual or group format. The presence of prominent family conflict, stressful life events, or poor social supports might be appropriate indications for inclusion of psychotherapy in a treatment plan (81). Psychotic or bipolar features, significant personality disorder symptoms, heightened suicidal risk, or substance abuse should, when possible, prompt the involvement of a mental health specialist to address the more complex and risky treatment courses associated with these attributes.
Individuals who are intolerant of medication and electroconvulsive therapy (ECT) or who prefer a psychosocial approach to treatment can be referred to a mental health specialist for a trial of psychotherapy in individual or group format. The presence of prominent family conflict, stressful life events, or poor social supports might be appropriate indications for inclusion of psychotherapy in a treatment plan (81). Psychotic or bipolar features, significant personality disorder symptoms, heightened suicidal risk, or substance abuse should, when possible, prompt the involvement of a mental health specialist to address the more complex and risky treatment courses associated with these attributes.
ANTIDEPRESSANT MEDICATION
Antidepressant treatment of late life depression, provided more frequently than psychotherapy, is the subject of several thorough and informative recent reviews (30,35,73,79,99,121). No specific agent or antidepressant class emerges as the clear preference, but medications are consistently shown superior to placebo treatment. Pharmacotherapy of late life depression is complicated by age-related pharmacodynamic and pharmacokinetic factors. In particular, the elderly show an increased sensitivity to anticholinergic and antidopaminergic side effects. These pharmacodynamic vulnerabilities are combined with the pharmacokinetic changes of delayed drug absorption, reduced oxidative metabolism, and diminished glomerular filtration and drug secretion. The net effects are slower attainment of steady-state kinetics, higher peak and steady-state serum drug levels, and, consequently, greater likelihood of adverse drug effects (145). Several of the newer antidepressants are inhibitors or substrates of the hepatic microsomal enzyme systems that interact also with commonly coadministered treatments for medical illnesses. Paroxetine, fluoxetine, and, to a lesser extent, sertraline inhibit the cytochrome P450 (CYP) 2D6 enzyme, potentially interfering with clearance of such coadministered medications as tricyclic antidepressants, selegiline, donepezil, dextromethorphan, codeine, meperidine, oxycodone, tramadol, encainide, flecainide, lidocaine, mexiletine, propafenone, metoprolol, propranolol, and timolol, among others. Nefazodone (infrequently prescribed following reports of rare but serious hepatic complications) and fluvoxamine are significant inhibitors of the CYP 3A4 enzyme, potentially interfering with clearance of several coadministered antidepressants, alprazolam, clonazepam, diazepam, midazolam, triazolam, buspirone, carbamazepine, lamotrigine, donepezil, acetaminophen, codeine, clarithromycin, erythromycin, ketoconazole, astemizole, tamoxifen, amiodarone, disopyramide, lidocaine, quinidine, calcium channel blockers, lovastatin, steroids, caffeine, and omeprazole, among others. Fluvoxamine also inhibits the CYP IA2 enzyme, potentially limiting clearance of drugs including clozapine and warfarin (145).
Table 31-1 lists the antidepressants and their dosages for use in late life depression. Most clinicians now initiate treatment with one of the selective serotonin reuptake inhibitors (SSRIs) or other newer serotonergic or nonserotonergic agents, citing data that support claims of their equal efficacy, more tolerable side effect profiles (fewer anticholinergic, cardiac, and cognitive adverse effects, although greater adverse effects on gastrointestinal and sexual functions), lower discontinuation rates, and better overall effect on quality of life. The availability of several generic serotonergic antidepressants has diminished the cost advantage sometimes previously cited as a reason for prescribing a tricyclic antidepressant.
Among the serotonergic medications, fluoxetine was shown in a large multicenter placebo-controlled, double-blind trial to be well tolerated in a group of patients 60 years of age and older (125), although the percentage of patients rated on the HAM-D as responders to 20 mg/day after 6 weeks was somewhat low (36% vs. 27% with placebo). The remission rate was 21% for fluoxetine and 13% for placebo in the intent-to-treat analysis, and the discontinuation and adverse effects rates for fluoxetine and placebo were similar. A large open study in which elderly depressed patients received fluoxetine (20 mg/day) showed a remission rate of 35% in the intent-to-treat analysis (71). At higher doses (20 to 80 mg/day), the efficacy of fluoxetine was equivalent to that of doxepin and its side effects were better tolerated in a group of elderly depressed outpatients (29). A lower dosage of fluoxetine is not required in the elderly, although treatment can be initiated at 10 mg/day to reduce the risk of overwhelming the patient with initial side effects. The side effects of fluoxetine, similar to those of other serotonergic antidepressants, include nausea and other gastrointestinal symptoms, headache, altered sleep, and sexual dysfunction. Weight loss has been cited as a clinical concern in particular with fluoxetine, but Goldstein et al. (36) reported that this is associated with pretreatment high body mass index. Hyponatremia, although an uncommon complication of SSRI antidepressants, is believed to be more common among elderly patients.
In a double-blind comparison to fluoxetine (20 to 40 mg/day), sertraline (50 to 100 mg/day) produced a similar decrease in mean HAM-D score after 12 weeks in a group of outpatients with a mean age of 74 years. Sertraline was claimed superior on the basis of greater cognitive improvement on one of three administered tests, better improvement on the Physical Health and Psychological Health subscale of the Quality of Life Enjoyment and Satisfaction Questionnaire, and nonsignificant statistical trends toward a higher rate of remissions and a lower number of dropouts (31). Sertraline’s linear kinetics (79), its lack of an active, long-acting metabolite, and its lesser inhibition of hepatic microsomal enzymes (101) are considered advantageous properties in treating the elderly. Treatment can be initiated at 25 or 50 mg/day in the elderly and titrated up to 100 to 150 mg/day.
Table 31-1. Selected Antidepressants for Use in Late Life Depression | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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The other SSRIs, too, have each been reported effective antidepressants in the elderly. Both sertraline and citalopram are characterized by a half-life appropriate for once-daily dosing, an absence of anticholinergic effects, and a minimum of drug-drug interactions. Their capacity to induce gastrointestinal side effects or sexual dysfunction appears on a par with the other selective serotonergic agents. In comparison with mianserin (30 to 60 mg/day), citalopram (20 to 40 mg/day) achieved similar rates of response in a group of elderly patients with and without dementia (44). Fluvoxamine has been compared with heterocyclic dothiepin, moclobemide, mianserin, and imipramine. Its efficacy has been reported as similar to these agents. Gastrointestinal side effects were the most common adverse effects, and cardiac effects were not significant (79). Paroxetine’s anticholinergic properties, nonlinear kinetics, and association with discontinuation symptoms can be considered relative drawbacks to its use. Escitalopram, although generally similar to other SSRIs, remains a more costly option until it becomes available as a generic medication.
Venlafaxine is a blocker of norepinephrine, serotonin, and dopamine reuptake that lacks anticholinergic, antihistaminergic, and antiadrenergic side effects. One double-blind comparison study (65) and several open series (9,28,51,126,143) support its efficacy and safety in the elderly. The double-blind comparison was of venlafaxine (50 to 150 mg/day) with dothiepin (50 to 150 mg/day). Response to therapy was seen in 60% of each group, and discontinuation as a result of adverse reactions was low with both venlafaxine (7%) and dothiepin (8%). The side effect profile of venlafaxine is similar to that of SSRIs, and it shares with paroxetine a short elimination half-life and propensity for inducing discontinuation symptoms. In addition, it is known to increase diastolic blood pressure in some patients (101) but appeared not to increase it in old patients more than in young patients in an open trial that included both age groups (143). Treatment in the elderly can be initiated at 37.5 mg/day and titrated up to the appropriate dose, often in the range of 150 to 225 mg/day.
Duloxetine resembles venlafaxine in its mechanism of action as a serotonergic reuptake inhibitor with additional effects on the reuptake of norepinephrine and dopamine. In addition, it has been promoted as effective in reducing various neuropathic pain symptoms. One secondary analysis of elderly subjects from two controlled studies found it to be more effective than placebo in patients aged 55 and older (77). A controlled study found 60 mg/day to be well tolerated and effective in reducing back pain and depression. Benefits were also demonstrated on ratings of verbal learning and memory (90).
Nefazodone, a serotonin reuptake blocker with 5-hydroxytryptamine-2 (5-HT2) antagonism, has not been specifically studied in groups of elderly depressed patients. Its lack of alteration of sleep architecture may be an advantage (12), and some clinicians advocate its use because of anxiolytic effects, but safety concerns aroused by a report of three cases of subfulminant liver failure associated with nefazodone (11) have led to its relative abandonment. If nefazodone were to be prescribed to an elderly patient, it would be prudent to initiate treatment at half the usual starting dose for younger adults (i.e., 50 mg twice daily) and to be alert to the potential drug-drug interaction effects resulting from nefazodone’s inhibition of the hepatic microsomal enzyme CYP 3A4, which would increase blood levels of several potentially coadministered medications (101).
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