Diagnosis and Management of Depression in the Elderly
Author: David Bienenfeld, MD, Professor and Vice Chair, Department of Psychiatry, Wright State University, Dayton, Ohio.
Peer Reviewer: Jerald Kay, MD, Professor and Chair, Department of Psychiatry, Wright State University, Dayton, Ohio.
Editor’s Note—When the losses, threats, and stresses of late life give rise to depression, older people are likely to turn first to their primary care physicians (PCPs) for help. Coming to the office with complaints of fatigue or generalized somatic discomfort, they may quickly be found to display emotional disturbances. The physician can easily be confused by the many displays of depressive conditions in the elderly and might be tempted to regard such distress as an inevitable consequence of aging in contemporary society. Treatment of geriatric depression in a frail population often seems like a daunting task.
Depression in the elderly, however, can be recognized and characterized with some clarity. Secondary depression due to medical illness or treatment must be identified. Treatment options include antidepressants, psychotherapy, and electroconvulsive therapy.
Epidemiology
Among community-dwelling Americans older than age 65, the point prevalence of major depression is 1-4%, compared with 3-5% across all age groups. But when combined with minor depressive syndromes, the prevalence among elderly in the community is about 15%. In primary care settings, depressive syndromes have been detected in about 20% of patients; in nursing homes, up to 30%.1-4 Risk factors for depression regardless of age, include:
• female sex;
• unmarried status;
• poverty;
• social isolation;
• prior history of depressive illness.
Additional risk factors in older individuals include:
• loss or grief;
• caretaking responsibilities;
• medical illness in self or spouse.5
The relative decrease in detection of major depression in older adults may be a function of cohort effect, prevalence of dementia, losses to suicide, or age-biased diagnostic criteria.3 In any event, fully 50-70% of cases of major depression go undetected by PCPs. Since 15% of elderly depressives will die of suicide and more than three quarters of those who commit suicide have seen the PCP within the prior month, it is essential for the PCP to recognize depression in the aging patient.6,7
Stress and Strain
At first blush, it seems easy to understand why depression is so common in latter years. Aging is hard. The body becomes more vulnerable to disease and disability. Friends and relatives become ill and die. The elderly are at risk for the loss of financial security and their familiar living environments. And, in a youth-centered culture such as ours, older people are threatened with an even greater loss: the loss of respect of others. As one wag put it: "Old age ain’t for sissies." So it is tempting to conclude that because life is stressful, people get depressed. But this formulation is suspect.
First, concluding that depression is a "normal" reaction to age-related difficulties is analogous to thinking that it is "normal" for someone with a gunshot wound to the abdomen to lose a liter of blood every few minutes. Just because a response may be normative doesn’t mean it is not pathological. Depression is suffering, and it demands attention.
Second, the relationship between stressors and depressive outcome has always proven to be empirically tenuous. Even though most people undergo the same stressors, the majority are not depressed. One person may become suicidally depressed at the death of a spouse, while another sees it as relief for both parties from longstanding suffering. Some people are devastated by retirement—others experience it as a rebirth. Perhaps the more fitting question is, with all the hard things about getting old, why are most old people not depressed?8
These losses and threats constitute stressors. Stress is something external to individual and results in symptoms only when it produces strain. The vulnerability to strain is a characteristic of the host, just as different individuals have different susceptibility to the same exposure to a viral infection. Psychological resistance is a product of defense mechanisms, perceptual prejudices, and behavioral responses that are gathered under the rubric of coping. Because the range of stressors in late life is so broad, it is the person with the widest range of coping skills who will be most able to adapt; the person with a limited range of coping skills will be more vulnerable to experiencing strain, which is often manifest as depression.9
Recognition
Older patients in particular are often not accustomed to putting feelings into words and may instead describe, "bad nerves," or "funny feelings all over." The clinician can help by offering mood statements, such as, "You sound sad," or, "Are you feeling blue?" It is useful to pay as much attention to facial expression and tone of voice as to the content of speech.10
Most clinicians are familiar with the classic "neurovegetative" signs of depression: insomnia, anorexia, constipation, and diminished libido. These features become less discriminatory as people age. Sleep problems are commonplace in late life, appetite normally diminishes with age, constipation is endemic among the elderly, and few practitioners would comfortably define what constitutes abnormal libido in a 75 year-old person.
More useful than these traditional features are the melancholic symptoms listed in the DSM-IV:11
• Loss of pleasure (anhedonia) or loss of reactivity of mood to environmental events
• Psychomotor agitation or retardation
• Early morning wakening or midnight wakening
• Pathological guilt
• Diurnal variation (typically feeling worst in the morning and better in the afternoon or evening)
• Weight loss (> 5% over a few months or less)
These signs and symptoms may be indicative of neurotransmitter dysfunction and tend to correlate with the likelihood of antidepressant response.
Patterns of Depression
Depression is not a homogenous entity. People bring to their physicians different patterns that may be organized as depression the symptom, depression the syndrome, and depression the disease (see Figure). One person may have elements of two or three patterns simultaneously.
As a symptom, depression may represent simple sadness, grief, mourning, or an adjustment disorder with depressed mood. Patients with this pattern come to the physician describing a subjective sense of psychological distress, linked by the patient to an identifiable loss or threat. They will typically complain of tearfulness, nervousness, pessimism, guilt, or diminished interest or energy, and they may have some melancholic features. Past history or family history of affective disorders is not remarkable in this group.
These are patients for whom the major thrust of therapy will be overcoming or adapting to loss. It helps the patient first to see the sense in a frightening situation and to know that he/she is not crazy. Such patients will often need permission to mourn, as family and others may discourage it. Education to families on this count is important, and elders need a context in which to mourn at their own pace without guilt. Such patients may also benefit from temporary symptomatic treatment with antianxiety agents or hypnotics. They typically do not need antidepressant treatment.
Patients with a depressive syndrome experience a general sense of dysphoria resulting from a particular characteristic vulnerability to environmental stressors. They come to clinical attention with a more chronic and pervasive disturbance of mood, affect, and behavior than those with grief or sadness; the relationship of mood to precipitant is more tenuous. The subjective sense of sadness is often lost in a cloud of negativism, anxiety, and worry. Affective disturbances may be overshadowed by fatigue, accident-proneness, or forgetfulness. Melancholic signs are not uncommon. If these signs are present, antidepressants are likely to be of help.
But these people often suffer from chronic depression because they have deficient coping capacities. Medication may relieve some of the symptoms, but leaves much of the distress. Thus, formal psychotherapy is generally necessary for optimal treatment outcome. At the least, psychiatric referral can tell the PCP if medication is likely to be helpful and if psychotherapy is indicated.
Depression may present itself as a disease, in the form of major depression or the depressed phase of bipolar disorder. These patients come to attention with a profound sense of sadness, hopelessness, guilt, or despair, or sometimes just nameless fear or agitation. They may well be psychotic at the time of first presentation. Melancholic features are almost invariably present and are more severe than in a depressive syndrome. A credible link to any environmental precipitant is rare.
These people have a disease of the brain. They need somatic treatment for their depression. Paradoxically, they may be easier to treat in the primary care or long-term care setting than those with less severe depressions because the vulnerability of their coping mechanisms is not an issue. Consultation from a psychiatrist may help the PCP choose the best antidepressant or decide if hospitalization or electroconvulsive therapy (ECT) would be better choices. But most can be managed if recognized properly and treated aggressively.
Suicide
The assessment of geriatric depression is not complete without an evaluation of suicide risk. Rates of suicide are alarmingly high and about one in seven people with serious depression will die at his/her own hand. It is most notable that older people make relatively fewer unsuccessful suicide attempts than younger ones; thus, the clinician has fewer chances to intervene and prevent such deaths.12
Risk factors for suicide can be recalled with the mnemonic "SAD PERSONS" (see Table 1). Sex and age are interactive; women’s risk peaks between 55 and 65 years of age, men’s risk continues to rise after age 60. Rational thinking can be impaired by late-life cognitive disorders. Physical illness, social isolation, unemployment, and alcohol use are particularly strong correlates of suicide risk.13,14
| Table 1. Risk Factors for Suicide |
| Sex |
| Age |
| Depression |
| Previous attempt(s) |
| Ethanol abuse |
| Rational thinking impairment |
| Social supports lacking |
| Organized plan |
| No job |
| Sick |
PCPs are advised to recall the "Rules of Sevens":12-14
• One in seven recurrent depressions ends in suicide.
• 70% of suicides suffer from major depression.
• 70% of suicides have seen a physician (usually a PCP) within the prior six weeks.
• Suicide is the seventh leading cause of death in the United States.
Depression Secondary to Medical Conditions and Treatments
Particularly in the primary care setting, it is vital to consider medical conditions that may lie behind depressive symptoms. Some medical illnesses have features that resemble depression, such as the weakness and fatigue of anemia or diabetes. Other diseases, like Parkinson’s disease or stroke, can alter brain chemistry in ways similar to primary depression.
Table 2 lists some of the more important medical causes of secondary depressions. Major depression occurs in 40-50% of patients with Parkinson’s disease and is associated with poorer motor and cognitive function than in non-depressed Parkinson’s patients.15 At least one in four stroke victims will suffer an episode of depression.16 Similarly, the risk of major depression in cancer patients is about 25%, particularly with metastatic visceral malignancies; an additional 25% will suffer from dysthymic disorder or adjustment disorder.17
| Table 2. Medical Conditions Associated with Depression22 |
| Central Nervous System Disorders |
| Parkinson's disease |
| Stroke |
| Tumors |
| Endocrine Disorders |
| Diabetes |
| Thyroid |
| Cancer |
| Infections |
| Common flu |
| Pneumonia |
| Anemia |
| Autoimmune disorders |
| Polymyalgia rheumatica |
| Temporal arteritis |
| * Adapted from Conn DK22 |
Notably absent from the list of medical conditions associated with depression is menopause. The common wisdom that menopause carries with it a vulnerability to affective illness is not substantiated by empirical study. Except in the case of surgical menopause or in women with a prior history of depression, depressive illness is no more common in menopausal women than in nonmenopausal peers. When depression does appear in such women, it should be evaluated and treated as a condition warranting its own attention.18-21
Not only medical disorders, but also the treatments commonly prescribed to aging patients can produce depressive features (see Table 3). Since depressed elders frequently exhibit anxiety, prescription of benzodiazepines is tempting. However, these agents do not treat depression, they can exaggerate the apathy and withdrawal of depression, and their use can lead the clinician to postpone initiation of definitive antidepressant treatment. Antipsychotic medications, given to people without frank hallucinations or delusions, can produce dysphoria and other depressive features. They are often prescribed for people with dementia who do not have formal psychoses. Among the antihypertensive agents, only those with central nervous mechanisms of action are worrisome; calcium channel blockers and ACE inhibitors are not likely to harm mood or affect.23
| Table 3. Medications Associated with Depression23 |
| Psychotropic |
| Benzodiazepines |
| Antipsychotics |
| Antiparkinsonian |
| L-Dopa |
| Amantadine |
| Antihypertensive |
| Propranolol |
| Methyldopa |
| Clonidine |
| Reserpine |
| Hydralazine |
| Other |
| Steroids |
Antidepressant Therapy
When melancholic features are present, antidepressant therapy is generally indicated. Of the major classes of antidepressants—tricyclics (TCAs), selective serotonin reuptake inhibitors (SSRIs), and newer mixed-action agents—all are approximately equally effective. About two-thirds of elders who complete a course of treatment will experience significant symptom relief from major depression. Thus, the selection of agents is generally based on tolerability and safety.24
Desipramine and nortriptyline cause limited pharmacodynamic or pharmacokinetic interactions with other drugs; however, they can be the target of such interactions. For example, SSRIs will increase serum levels of the TCAs.26
Selective serotonin reuptake inhibitors. These agents are, appropriately, the mainstay of antidepressant therapy in aging individuals. They have no a-1 adrenergic affinity; except for paroxetine, they have negligible muscarinic or histaminic blockade. Notably, they do not impair cognition. Their major side effects are the products of their therapeutic mode of action (i.e., enhancement of serotonin transmission). These effects are gastrointestinal (nausea, anorexia, diarrhea), central nervous (insomnia or sedation, nervousness, dizziness, tremor, headache), and sexual (diminished libido, anorgasmia, delayed ejaculation, impotence). All these effects are dose-related. Since SSRIs have a fairly flat dose-response curve, increasing drug dose generally increases adverse effects without substantially enhancing therapeutic effects.25,27
Drug interactions with SSRIs are complex because of their influence on the cytochrome P450 system. Fluoxetine is the widest and most potent inhibitor of P450 isoenzymes, paroxetine is moderately problematic, and sertraline and citalopram are the narrowest and least potent P450 inhibitors.
Other agents. Nefazodone is a weak inhibitor of serotonin reuptake but a potent antagonist at the 5-HT2 receptor. As a result, it does not produce sexual dysfunction, but often produces drowsiness—sometimes to a prohibitive extent. Other side effects may include nausea and dizziness. Nefazodone inhibits the CYP 450 3A isoenzyme, which is responsible for 50% of known oxidative drug metabolism, including its own metabolism.25,26
Venlafaxine is a mixed action, noradrenergic and serotonergic, antidepressant. It has no affinity for muscarinic, histaminic or a-1 adrenergic receptors. It may cause transient nausea, dizziness, nervousness, sexual dysfunction, and anorexia. Its drug interaction profile is similar to that of sertaline and citalopram.24,26,27
Mirtazapine has a novel mode of action, primarily blocking histamine-1 receptors (with some activity at 5HT2A, 5HT2C, 5HT3, and a-2 sites). The histamine-1 blockade produces a secondary increase in both noradrenergic and serotonergic transmission. It does not produce nausea or sexual side effects and does not alter sleep physiology. It is moderately sedating and usually causes increased appetite and weight gain. Because of its multiple loci of action, it can produce pharmacodynamic interactions with a variety of histaminergic, serotonergic, and a-adrenergic drugs. It has few pharmacokinetic (cytochrome P450) interactions.26,28
Bupropion is an antidepressant with mild dopaminergic activity. It is generally well tolerated, it has little anticholinergic activity, and it causes almost no sexual dysfunction. It does have a tendency to cause seizures at doses not far above the therapeutic range and must be given in multiple doses daily. Dosing is highly variable from patient to patient. Bupropion’s efficacy relative to the TCAs and SSRIs has been questioned. It may potentiate the action of co-administered dopaminergic and noradrenergic drugs, and bupropion levels can rise with concurrent administration of fluoxetine.25,26
Trazodone was a transitional drug between the TCAs and SSRIs. It is a weak serotonin-2A receptor antagonist. While it has a wide therapeutic index, it causes dose-dependent drowsiness, dizziness, and confusion. Its adrenergic blocking properties cause constipation and postural hypertension. The efficacy of trazodone in geriatric populations has not been widely studied. Its drug interaction profile is similar to that of nefazodone.26
Table 4 provides a comparison of the major antidepressants useful in older patients in primary care.
| Table 4. Comparison of Major Antidepressants25-29 | ||||||
| Drug | Significant active metabolites | Plasma half-life parent plus active | Muscarinic anticholinergic effects | Sedation | Agitation, nervousness, insomnia | Geriatric dose initial/maximum (mg/d) |
| TCAs | ||||||
| Desipramine | Yes | 24-96 h | Moderate | Moderate | Rare | 10/150 |
| Nortriptyline | Yes | 36-48 h | Moderate | Moderate | Rare | 10/100 |
| SSRIs | ||||||
| Citalopram | Yes | 36-90 h | None | Little/none | Rare | 10/40 |
| Fluoxetine | Yes | 8-18 d | None | Little/none | Common | 10/80 |
| Paroxetine | No | 30 h | Moderate | Moderate | Rare | 10/40 |
| Sertraline | No | 36 h | None | Mild | Rare | 25/200 |
| Other | ||||||
| Mirtazapine | No | 40-60 h | None | Moderate | Rare | 15/45 |
| Nefazodone | Yes | 24 h | None | Severe | None | 200/600 |
| Venlafaxine | Yes | 12 h | None | Mild | Common | 37.5/300 |
Some depressive symptoms may begin to resolve within a short while, but most will take several weeks. In the elderly, the time course of response may be even further prolonged, and full antidepressant response may not occur for as long as two months, even at full antidepressant dose. Once remission is achieved, the full dose of antidepressant should be continued for a minimum of two years (compared with 6-9 months in younger patients). While conventional wisdom may lead the practitioner to reduce the acute antidepressant dose for maintenance therapy, this practice is not generally successful and is not supported by research. At all ages, "the dose that gets you better is the dose that keeps you better."30,31 Since the risk of relapse increases with age, and since severity of depression increases with recurrent episodes, lifetime maintenance therapy is recommended by many experts (see Table 5).30-32
| Table 5. Indications for Lifetime Maintenance Antidepressant Therapy | ||||||
| Age 50 or older at first episode | ||||||
| Three or more episodes at any age | ||||||
| Two episodes and: | ||||||
| • Age 40 or older | ||||||
| • Family history of recurrent major depression | ||||||
| • Family history of bipolar disorder | ||||||
| • First episode before age 20 | ||||||
| • Both episodes severe or life threatening within the prior three years | ||||||
Tricyclic antidepressants. Most TCAs have both adrenergic and serotonergic therapeutic actions. Unfortunately, they also act at other neurotransmitter sites that contribute to their many side effects. Muscarinic anticholinergic effects include dry mouth, urinary retention, diminished visual accommodation, cognitive impairment, and tachycardia. Histaminic effects include sedation, increased appetite, and weight gain. Alpha-adrenergic blockade causes orthostatic hypotension. Additionally, all TCAs have Type I antiarrhythmic effects, which may adversely affect cardiac conduction. Most worrisome, TCAs are potentially lethal in overdose and have a much narrower ratio of toxic to therapeutic dose than most other treatment options.24,25
Tertiary amine TCAs (e.g., amitriptyline, imipramine) have more numerous and more intense side effects than secondary amine agents, and should rarely, if ever, be prescribed for elderly patients. Secondary amines, such as nortriptyline and desipramine, are somewhat safer and better tolerated.25
Electroconvulsive Therapy (ECT)
While ECT is certainly not in the armamentarium of the PCP, it remains an invaluable intervention for treatment-refractory depression at all ages and remarkably safe and effective in late life. In primary major depression, ECT induces remission in 80-90% of patients, and its efficacy does not decrease with age. It is particularly indicated in patients who have failed to respond to, or who have been unable to tolerate, multiple antidepressants; and in those whose depression represents an imminent threat to health or survival. There is some indication that patients with delusional depression respond better to ECT than to antidepressants.33
Contemporary techniques of anesthesia and ECT stimulus have drastically reduced the adverse effects of cognitive impairment and damage to teeth and bones that were common several decades ago. Unilateral electrode placement is significantly less injurious to memory than bilateral placement. Adequate paralysis makes fractures and dislocations rare even in patients with severe osteoporosis.34
Psychotherapies
In those patients whose vulnerability to depression is based on inadequate coping mechanisms or maladaptive personality style, and in those who experience depressive symptoms in the face of major life stressors, psychotherapy is no less valuable in late life than it is in earlier adulthood. A number of modalities have proven useful in elderly patients.35
Psychodynamic psychotherapy. This examines the patient’s interpretation of life events and his/her defense mechanisms. Unconscious feelings or conflicts are brought to light, and more adaptive interpretations are adopted.
Cognitive therapy. This sees depression as a result of self-defeating thinking patterns. The therapist helps the patient identify automatic thoughts that lead to feelings of hopelessness and futility. Patient and therapist test the veracity of these beliefs and undertake experimental adoption of more adaptive cognitions. Behavioral homework is a vital feature.
Interpersonal therapy. This focuses on losses and role transitions as stressors underlying depression. The therapy helps the patient identify these effects and reformulate his/her role in the social environment.
Group therapy. This can provide an opportunity for depressed elders to break the shell of depressive isolation. Identification with others and confrontation of self-defeating beliefs and behaviors, help the patient overcome depressive ideation and behaviors.
Family therapy. This may be a useful adjunct to individual treatment. Families may discourage the expression of depressed feelings and may distance themselves from the depressed elder. Family stressors may be the precipitant for the depression. With identification and clarification, the family can become allies of the treating physician.
Summary
While most people negotiate the currents of late life without emotional disturbance, a large number experience the pain of depression. The PCP is often the first source of contact for them. Depression may present as a reaction to stressful developments, a pattern of maladaptive coping, or an episode of severe emotional illness. Depression can also be a secondary effect of the diseases to which the elderly are subject and to the medications they may be prescribed.
With proper recognition, the PCP can implement safe and effective treatment. The SSRIs are generally efficacious and well tolerated, and there is a range of other pharmacologic agents available. After consultation, psychotherapy may be recommended in addition to, or instead of, medication.
Usually, therapeutic outcome in older adults with depression is encouraging. By identifying the condition and implementing treatment, the physician can restore pleasure and meaning to his/her depressed patients’ lives.
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