Essentials of Diagnosis
Loss of interest or pleasure in almost all activities.
Unintentional weight change, lack of energy, change in sleep pattern, psychomotor retardation or agitation, excessive guilt, or poor concentration.
Suicidal ideation or recurrent thoughts of death.
Somatic rather than mood complaints in the elderly.
General Principles in Older Adults
By 2020, depression will rank second only to cardiovascular disease as a cause of global disability and a major public health problem in older people. The prevalence of major depression is estimated at 1% to 2% for elders in the community and 10% to 12% for those in primary care settings. However, even in the absence of major depression as defined by Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria, up to 27% of elders experience substantial depressive symptoms that may be relieved with intervention. For institutionalized elders, the rates of major depression are much higher: 12% for hospitalized elders and 43% for permanently institutionalized elders.
The World Health Organization Primary Care Study reported that 60% of primary care clinic patients treated with antidepressant medication still met criteria for depression 1 year later, with similar efficacy rates for antidepressants reported in older adults and those younger than the age of 60 years. However, depression is often missed or inadequately managed in older adults, sometimes because of the belief that depression is an inevitable process of aging or because treatment may be risky or ineffective. Indeed, there are several reasons why optimal treatment of depression in the geriatric population may differ from that for younger populations. Higher rates of physical and cognitive comorbidity in older adults, different social circumstances, greater potential for polypharmacy, and age-related pharmacodynamic and pharmacokinetic susceptibility all suggest that this population should be considered separately.
Women are twice as likely to experience major depression as men. Other risk factors include prior episodes or a personal family history of depression, lack of social support, use of alcohol or other substances, and a recent loss of a loved one. Several medical conditions are also associated with an increased risk of depression, including Parkinson disease, recent myocardial infarction, and stroke. These conditions share common threads of loss of control of body or mind, increasing dependence on others, and increased social isolation.
Depression is associated with poorer self-care and slower recovery after acute medical illnesses. It can accelerate cognitive and physical decline and leads to an increased use and cost of health care services. Among depressed older adults who have had a stroke, rehabilitation efforts are less effective and mortality rates are significantly higher.
Major depression is defined as depressed mood or loss of interest in nearly all activities (anhedonia) or both for at least 2 weeks, accompanied by a minimum of 3 or 4 of the following symptoms (for a total of at least 5 symptoms): insomnia or hypersomnia, feelings of worthlessness or excessive guilt, fatigue or loss of energy, diminished ability to think or concentrate, substantial change in appetite or weight, psychomotor agitation or retardation, and recurrent thoughts of death or suicide. Severity of depression varies and is important in determining optimal treatment and prognosis. Mild depression is marked by few, if any, symptoms in excess of the minimum number required to meet the diagnostic criteria defined above, and it is accompanied by minimal impairment in functioning. Moderate depression includes a greater number and intensity of depressive symptoms and moderate impairment in functioning. Patients with severe depression experience marked intensity and pervasiveness of depressive symptoms with substantial impairment in functioning. Patients with less-severe depressive symptoms who do not meet criteria for major depression may also benefit from psychotherapy and pharmacotherapy.
Older patients can have fewer mood and more somatic complaints, which are often difficult to differentiate from underlying medical conditions. Special screening tools that consider this difference have been developed for the older population. The Geriatric Depression Scale is widely used and validated in many different languages. Its shortened 15-item scale (Table 45–1) is often used for ease of administration. A separate 2-item scale consisting of 2 questions about depressed mood and anhedonia has also been shown effective in detecting depression in older adults (see Table 45–1). Screening alone has not been found to benefit patients with unrecognized depression, but in combination with patient support programs, such as frequent nursing follow-up and close monitoring of adherence to medication, it improves outcomes.
Table 45–1.Geriatric depression scale (short form).a ||Download (.pdf) Table 45–1. Geriatric depression scale (short form).a
|Depression Scale || |
|1. Are you basically satisfied with your life? ||Yes/No |
|2. Have you dropped many of your activities and interests? ||Yes/No |
|3. Do you feel that your life is empty? ||Yes/No |
|4. Do you often get bored? ||Yes/No |
|5. Are you in good spirits most of the time? ||Yes/No |
|6. Are you afraid that something bad is going to happen to you? ||Yes/No |
|7. Do you feel happy most of the time? ||Yes/No |
|8. Do you often feel helpless? ||Yes/No |
|9. Do you prefer to stay at home rather than going out and doing new things? ||Yes/No |
|10. Do you feel that you have more problems with memory than most? ||Yes/No |
|11. Do you think it is wonderful to be alive now? ||Yes/No |
|12. Do you feel pretty worthless the way you are now? ||Yes/No |
|13. Do you feel full of energy? ||Yes/No |
|14. Do you feel that your situation is hopeless? ||Yes/No |
|15. Do you think that most people are better off than you are? ||Yes/No |
|SCORE: ||_________ |
|Directions: Score 1 point for each bolded answer. A score of 5 or more is a positive screen for depression. || |
|Two-Question Case-Finding Instrumentb || |
|During the last month, have you often been bothered by feeling down, depressed, or hopeless? ||Yes/No |
|During the last month, have you often been bothered by having little interest or pleasure in doing things? ||Yes/No |
|Directions: Yes to either question is a positive screen for depression. || |
Diagnosing depression in older adults can be challenging because of the presence of multiple comorbid conditions. Many patients with mild cognitive impairment may have predominantly depressive symptoms. With effective treatment of depression, their cognitive performance frequently improves; however, their risk for developing dementia in their lifetime is roughly double the risk of nondepressed seniors. Bereavement often manifests with depressed mood, which may be appropriate given a patient’s recent loss. However, if depressive symptoms persist, further evaluation may be warranted.
Older patients who experience delirium caused by an underlying medical illness may have mood changes. Other comorbid psychiatric illnesses must also be considered, such as anxiety disorder, substance abuse disorder, or personality disorders. Patients with bipolar disorder or psychotic disorders may have depressed mood; thus, it is important to ask patients about prior manic episodes, hallucinations, or delusions.
Depression can also be confused with other medical conditions. Fatigue and weight loss, for example, may be associated with diabetes mellitus, thyroid disease, underlying malignancy, or anemia. Patients who have Parkinson disease may first present with depressed mood or flat affect. Sleep disturbances as a result of pain, nocturia, or sleep apnea may also lead to daytime fatigue and depressed mood.
A complete history and physical examination, including assessment of cognitive status, is critical in the evaluation of depression in older adults. Because depression is a clinical diagnosis, no routine laboratory tests are indicated. Testing may be tailored to each patient based on their underlying comorbidities and presenting symptoms. A complete review of medications, both prescription and nonprescription, is essential. Medications, such as benzodiazepines, opioid analgesics, glucocorticoids, interferon, and reserpine, may cause depressive symptoms. Contrary to earlier beliefs, β blockers have not been proven to cause depression. Screening for alcohol and other substance use or addiction is another important part of the medical history. Substance use can interfere with compliance and contribute to high relapse rates, although active substance abuse should not preclude treatment for depression. For patients who struggle with addiction, “dual diagnosis” programs (alcohol or other substance dependence and psychiatric disorder) may be optimal.
Patient & Family Education/Supportive Care
Educating patients and families about depression is the cornerstone of successful treatment. Depression continues to carry a stigma in many communities and cultures. Appropriate education can help patients understand that their condition results from a combination of inherited factors and personal and environmental stressors. Providers should also emphasize that physical symptoms and sleep disturbances are characteristic of depression; thus, relief of depression could make other physical symptoms more bearable. Encouraging physical activity with a family member or friend can be a simple, effective step toward improving social support and overall well-being.
Involving families in the care of older patients is crucial for both diagnosing depression and developing an effective treatment plan. However, caregivers of older patients, especially if impaired physically or cognitively, may experience considerable stress and depression as well. Referred to as caregiver burden, this is an all-encompassing term used to describe the physical, emotional, and financial toll of providing care. In particular, when patients with dementia have depression, their caregivers report higher levels of burden. Many programs are available that may alleviate stress and promote positive social interactions for patients. Adult day programs, senior centers, and senior support groups can be helpful resources for patients and their families, and geriatric social workers can assist with finding appropriate programs for each patient. Caregiver support groups and formal respite programs are also available in many communities.
Overall, antidepressants, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and selective serotonin-norepinephrine reuptake inhibitors (SNRIs), are equally effective in the treatment of geriatric depression. However, because of side-effect profiles and propensity for drug interactions, monoamine oxidase inhibitors (eg, phenelzine and tranylcypromine) and tertiary amine TCAs (eg, amitriptyline, imipramine, and doxepin) are rarely used in older adults. The SSRI class includes citalopram, escitalopram, fluoxetine, paroxetine, and sertraline; examples of SNRIs are venlafaxine, desvenlafaxine, and duloxetine. Fluoxetine is generally avoided in older adults because of its long half-life and inhibition of the P450 system. Choice of therapy among the remaining drugs is generally determined by side-effect profile and the patient’s comorbid symptoms such as anxiety, insomnia, pain, and weight loss, although anxiety and insomnia do not necessarily predict a better response to more sedating medications. Renal and hepatic functions are also important considerations in older adults and should be assessed before initiation of therapy.
SSRIs are relatively safe in overdose. Thus, they are a reasonable first choice in treating older patients with depression. However, the Food and Drug Administration has recently posted a warning of cardiac arrhythmias associated with high doses of the SSRI citalopram hydrobromide (Celexa). Citing increased risk of QT interval prolongation and torsade de pointes through postmarketing reports of citalopram, the FDA announced a maximum daily dose of 20 mg for all patients older than age 60 years. The warnings do not apply to its racemic drug, escitalopram (Lexapro), which is the S-enantiomer of the citalopram molecule.
Other agents offer unique advantages: Mirtazapine stimulates appetite and can help with insomnia, and bupropion can reduce craving in smoking cessation. Secondary amine TCAs (eg, nortriptyline, desipramine) can offer beneficial effects for patients with neuropathic pain, detrusor instability, or insomnia. SNRIs, which have serotonergic and noradrenergic activity, are other effective alternatives that may also be useful in treating anxiety and neuropathic pain.
In general, older patients should begin an antidepressant by taking half of the manufacturer-recommended starting dose (to minimize side effects), but the medication should be titrated to the recommended target dose in weekly increments. Older patients are frequently undertreated because the provider fails to adequately titrate the dose to a therapeutic level. If minimal or no benefit occurs by 4–6 weeks and side effects are tolerable, the dose should be increased. The full effect may not be seen for 8–12 weeks in older patients. If a therapeutic dose has been reached and maintained for 6 weeks and the patient has not adequately responded, one should consider switching to a different agent or augmenting with an additional agent. Although serum drug levels are not useful for SSRIs, levels of TCAs can be measured to assess adherence.
Side effects differ depending on the type of antidepressant. Most side effects lessen within 1–4 weeks from the start of therapy, but weight gain and sexual dysfunction may last longer. For the SSRIs, the most common side effects include nausea and sexual dysfunction. Sexual dysfunction may respond to treatment with sildenafil, but switching antidepressant medication or lowering the dose of SSRI and augmenting with an additional agent may be necessary. The TCAs have more anticholinergic properties and may lead to dry mouth, orthostasis, and urinary retention.
Cardiovascular disease—TCAs can be associated with orthostatic hypotension and cardiac conduction abnormalities, leading to arrhythmias. Recently, citalopram has been implicated in potentially dangerous arrhythmias. Therefore, electrolyte and/or electrocardiographic monitoring is recommended for patients at risk for arrhythmias if these agents are considered.
Hypertension—Venlafaxine and desvenlafaxine may increase systolic and diastolic blood pressure.
Electrolyte abnormalities—Serotonin-reuptake inhibitors may induce hyponatremia.
Hepatic disease—Most antidepressants are hepatically cleared and should be used with caution in patients with liver disease. Nefazodone in particular should not be used in patients with liver disease or elevated transaminases because it has been associated with an increased risk of hepatic failure and interacts with other hepatically cleared medications, including simvastatin and lovastatin.
Falls—Serotonin-reuptake inhibitors have been associated with an increased risk in falls particularly in older patients with dementia. Fall risk assessment should be included in part of overall medical evaluation.
Bleeding risk—Serotonin-reuptake inhibitors may increase bleeding risk and interact with anticoagulant medications such as warfarin. International normalized ratio levels should be closely monitored with initiation of treatment with SSRI’s.
Cognitive impairment—TCAs and certain SSRIs, such as paroxetine, have stronger anticholinergic effects and should be avoided in patients with cognitive impairment to avoid increasing confusion.
Seizure disorders—Bupropion lowers seizure thresholds.
Suicidal ideation—TCAs are lethal in overdose and should be avoided in actively suicidal patients. SSRIs and SNRIs are relatively safe in overdose.
Serotonin syndrome—Use of serotonergic antidepressants may lead to serotonin syndrome, a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. Although classically described as a triad of mental status changes (headache, confusion, agitation), autonomic hyperactivity (diaphoresis, hypertension, tachycardia, nausea, diarrhea), and neuromuscular abnormalities (tremor, myoclonus, hyperreflexia) serotonin syndrome can span a spectrum of clinical findings ranging from benign to lethal. Given the increased use of serotonergic agents in medical practice, and the syndrome’s potential for rapid onset, with its clinical course developing over 24 hours, providers are advised to remain vigilant for this condition. The central principles to the management of suspected serotonin syndrome are (a) discontinuation of all serotonergic agents, and (b) supportive care aimed at normalization of vital signs.
Psychostimulants, such as dextroamphetamine (5–10 mg/day) or methylphenidate (2.5–5 mg/day), are sometimes indicated as either a primary or an adjuvant treatment for depression with predominant vegetative symptoms. A newer stimulant, modafinil (Provigil), which increases monoamines, has also been used as an adjunct to traditional antidepressants. With its additional histaminergic effects, modafinil is considered by some to be a “wakefulness promoting agent,” and unlike the classic amphetamine-like stimulants, is considered to have limited abuse potential. At the end of life, patients may not have time to wait 4–6 weeks for the benefits of antidepressant medication, and psychostimulants may offer more immediate relief. In the setting of depression after an acute medical illness, psychostimulants may offer a faster means to enhance recovery and participation in rehabilitation. Typical side effects include insomnia and agitation, but these may be lessened by taking the medication early in the day in divided doses (morning and noon). Another common side effect is tachycardia.
Many herbal remedies claim to be effective in treating depression, but further evidence is still needed to determine whether these “dietary supplements” (eg, Hypericum perforatum [St. John’s wort]) have a role in the treatment of depression. H. perforatum should not be used in conjunction with SSRIs because the combination may lead to serotonergic syndrome, which is characterized by changes in mental status, tremor, gastrointestinal upset, headache, myalgia, and restlessness. It may lower the concentration of certain drugs, such as warfarin, digoxin, theophylline, cyclosporine, and HIV-1 protease inhibitors. Other common herbal remedies such as kava kava and valerian root have not been proven effective for treating depression. Herbal remedies should not be substituted for proven depression therapies.
Cognitive–behavioral therapy (CBT), problem-solving therapy, and interpersonal psychotherapy are effective treatments for major depression, either alone or in combination with pharmacotherapy. CBT focuses on identifying negative thoughts and behaviors that contribute to depression and replacing them with positive thoughts and rewarding activities. Problem-solving therapy teaches patients techniques to identify routine problems, generate multiple solutions, and implement the best strategy. Interpersonal psychotherapy focuses on recognizing and attempting to resolve personal stressors and relationship conflicts that lead to depressive symptoms.
Typically, these therapies should be continued once or twice weekly for 6–16 sessions. In patients with severe depression, combination therapy with psychotherapy and pharmacotherapy is superior to either treatment alone. Psychoanalytic and psychodynamic therapies have not proved effective for treatment of major depression.
Electroconvulsive therapy (ECT) is an effective treatment for geriatric depression. Response rates for refractory depression are quite high at 73% for the young-old (age 60–74 years) and 67% for the old-old (age >75 years). Typical side effects include confusion and anterograde memory impairment, which may persist for 6 months. ECT may be first-line therapy for severely melancholic patients, for those at high risk for suicide, and for medically ill patients whose hepatic, renal, or cardiac diseases preclude the use of other antidepressants.
Psychiatric consultation is recommended for those patients with a history of mania or psychosis, for those who have not responded to a trial of 1 or 2 medicines, and for those who require combination therapy or ECT. Immediate psychiatric evaluation is required for any patients who, after probing, admit to having active plans to harm themselves. Risk factors for suicide in older patients with major depression include older age; male gender; marital status of single, divorced, or separated and without children; personal or family history of a suicide attempt; drug or alcohol abuse; severe anxiety or stress; physical illness; and a specific suicide plan with access to firearms or other lethal means (eg, stockpiled medications). If medications and weapons are present and cannot be removed from the patient’s home, consider adding “weapon at home” to the patient’s problem list to highlight potential suicide risk.
Older patients should be monitored closely during the initial 3 months of treatment. Many medical outpatients who receive a prescription for an antidepressant terminate treatment during the first month, when side effects may be at a maximum and before therapeutic effects are evident. Older patients should be monitored closely in the first 1–2 weeks of therapy to assess side effects and encourage continued therapy. They should have a minimum of 3 visits (in person or by telephone) during the first 12 weeks of antidepressant treatment.
Older patients must be informed that antidepressants usually take 4–6 weeks, but may take 8 weeks or longer, to have a full therapeutic effect and that only approximately 50% of patients respond to the first antidepressant prescribed. Patients who have not responded after an adequate trial of medication or who have had intolerable side effects may switch either to another medication within the same class (different SSRI) or to a different class of medications. When switching among SSRIs or between TCAs and SSRIs, no washout period is required (with the exception of switching from fluoxetine, because of its long half-life). However, abrupt cessation of shorter-acting antidepressants (eg, citalopram, paroxetine, sertraline, or venlafaxine) may result in a discontinuation syndrome with tinnitus, vertigo, or paresthesias. Referral for psychiatric consultation is recommended if a patient fails to respond to 2 different medication trials.
Once remission has been achieved, antidepressants should be continued for at least 6 months to reduce the risk of relapse. Patients who are at high risk of relapse (2 or more episodes of depression in the past or major depression lasting more than 2 years) should be continued on therapy for 2 years or possibly indefinitely. Many recommend lifelong therapy, even if it is the patient’s first episode of major depression and especially if depression is severe and related to life changes that are not expected to improve. Follow-up visits should be arranged at 3–6-month intervals. If symptoms return, the medications should be adjusted or changed or the patient referred for psychiatric consultation.
If the patient and physician agree to a trial discontinuation of therapy, medications should be tapered over a 2–3-month period, with at least monthly follow-up by telephone or in person. If symptoms return, the patient should be restarted on medications for at least 3–6 months.
When patients fail to respond to adequate trials of 2 medications for major depression, a diagnosis of treatment-resistant depression is considered. One must review the case and consider that the original diagnosis may be inaccurate. What first appeared as depressive symptoms may be a manifestation of underlying anxiety or cognitive impairment. Apathy may be one of the first symptoms seen in dementia prior to more obvious cognitive symptoms. One must then verify that the patient actually received the medication that was prescribed. A simple investigation may reveal that the patient never filled the prescription or was never given medication by caregivers. Finally, one must ensure that the patient had adequate trials of medications (6–8 weeks) and that this trial was performed at a therapeutic dose.
Any patient who has had an adequate trial of 2 different medications without acceptable response should be referred to a psychiatrist for augmentation therapy. As shown from the federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest real-world study of treatment-resistant depression, patients with persistent depression have the potential to improve after several medication treatment trials; however, the odds of remission diminish as additional treatment strategies are needed. Lithium may be used in low doses in older adults with careful monitoring of side effects. Small doses of liothyronine (T3) can be used safely in euthyroid patients. In addition, combinations of 2 antidepressant medications may be synergistic, with low doses of 1 antidepressant enhancing response to an antidepressant of another class.
Patients who have been referred to psychotherapy must still be monitored closely by their primary care clinicians because patients tend to discontinue therapy even more frequently than antidepressant treatments. The benefits of psychotherapy are generally evident by 6–8 weeks. The addition of pharmacotherapy should be considered for patients who have not fully responded to psychotherapy alone by 12 weeks. A combination of psychotherapy and pharmacotherapy may be more effective for moderate depression than either treatment alone.
Depression is often a chronic or relapsing and remitting disease. Greater severity of depression, persistence of symptoms, and a higher number of prior episodes are the best predictors of recurrence. The lifetime risk of suicide in patients with major depression is 7% for men and 1% for women.
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