Depression in the Elderly: A Pharmacist’s Perspective

Depression in the Elderly: A Pharmacist’s Perspective

Abstract

Depression is a disease state that is commonly underdiagnosed and undertreated in patients over the age of 65 years. Elderly patients may differ from younger patients in the presentation of symptoms and in the prevalence of comorbidities. Risk factors for the development of depression are different for elderly patients. Treatment may also be dissimilar, including response and response time to treatment. Treatment should be tailored to the individual patient in the geriatric population to optimize therapeutic outcomes. Pharmacists can be vigilant of comorbidities and medications that potentially increase the risk of depression in the elderly. Pharmacists can play a significant role in advocating for the screening and treatment of this disease state. They are in a unique position to improve patient outcomes in late-life depression.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines late-life depression as depressive symptoms in adults older than 65 years of age. This includes elderly patients who have experienced a mood disorder for the first time in later life and those whose symptoms initially presented earlier in life and are now recurring. The diagnosis of depression in older patients utilizes the same criteria as young adults. The diagnosis may be more difficult in the elderly due to coexisting chronic medical conditions and medication use, disability, or cognitive decline.1 Depression in the elderly population is widespread and is often underdiagnosed and inadequately treated. Healthcare personnel who oversee care of the elderly may not be equipped to recognize or treat patients with depression. This is likely due to the presentation of depression in the elderly, which is often atypical—insomnia, anorexia, and fatigue—as opposed to the typical depressed mood reported by the younger depressed patient. Rather than reporting feeling sad or depressed, elderly more often have somatic complaints such as chronic pain, weight loss, headache, or gastrointestinal symptoms.2 The elderly often dismiss their less-severe depressive symptoms as an acceptable response to life stress or a normal part of aging; however, depression is not a normal consequence of aging. Late-life depression, when untreated, has a significant impact on a patient’s quality of life, healthcare resources, functional status, morbidity, and mortality.3,4 Late-life depression should be treated with antidepressants that are safe in geriatrics and carefully chosen to meet each patient’s needs.

Epidemiology

There are over 39 million adults aged 65 years and older in the United States and an estimated 7 million of these are affected by depression.5 About 5% of community-dwelling older adults meet the criteria for a major depression diagnosis. In institutional settings, the incidence of depression in the elderly population ranges from 12% to 30% and increases up to 50% among long-term care residents.6 By 2020, the World Health Organization predicts that in developed countries, depression will be the second leading cause of disability and untimely death, after heart disease.2

Risk Factors for Geriatric Depression

Risk factors for depression in elderly persons include a family history of depression; chronic medical illness; use of certain medications; female gender; single, widowed, or divorced marital status; those with social isolation; lower socioeconomic status; and, stressful life events. Significant life events have been identified that increase an older adult’s risk for depression. These include death of a spouse or loved one, disease or injury, disability and functional impairment, and loneliness.7

In a meta-analysis, 5 major risk factors for depression in older adults were reported. These risk factors included grief, sleep problems, disability, previous episodes of depression, and female gender. Of these, sleep issues, grief, and disability may be potentially modified.8

Comorbidities

Rates of depression are higher for elderly patients with coexisting medical conditions. Older adults with possible depression should have a complete physical examination, medication history, and necessary laboratory assessment to rule out medical conditions such as hypothyroidism, alcohol use, or prescription drug abuse that may contribute to depression.

Untreated depression may result in patients developing chronic medical illnesses such as cardiovascular disease, and worsening others such as diabetes mellitus and Alzheimer’s disease.9-11 Depressed patients with comorbid diabetes are at greater risk for decreased adherence to medications, poor diet, decreased physical activity, higher functional impairment, and increased healthcare costs compared to their nondepressed peers.12,13

A number of medical illnesses have been reported to have the highest rates linked to late-life depression. Nearly 25% to 50% of all stroke patients develop depression post stroke.14-16 Major depression also may affect 20% to 25% of patients with Alzheimer’s disease.17 Other medical illnesses include cancer (18%–39%), Parkinson’s disease (10%–37%), rheumatoid arthritis (13%), diabetes (5%–11%), and myocardial infarction (MI) (15%–19%).18

The American College of Cardiology and the American Heart Association recommend screening for and treating depression for secondary prevention in patients with ST-segment elevation MI. Evaluation is recommended while hospitalized, 1 month after hospital discharge, and yearly.19

Researchers have reported that depression in the hospital after an MI is a significant predictor of 1-year cardiac mortality for both men and women. Depressed patients were significantly more likely to die of cardiac causes and to have an arrhythmic episode than patients without depression.20

Common psychiatric comorbidities of depression have been reported in a cohort study of 378 older depressed patients. Rates of anxiety-related disorders included any anxiety (41%), social phobia (19.6%), agoraphobia (10.8%), generalized anxiety disorder (10.6%), and panic disorder (7.7%).21

Medications That Cause Depression

A number of medications are believed to be capable of causing depression. Although these medications may be associated with depression, there have been no studies assessing the risk they pose above and beyond that normally present in geriatric patients with comorbid disease states. Case reports, post-marketing surveillance, and retrospective studies have linked the following medications with depression: antipsychotics, digoxin, hydralazine, efavirenz, antineoplastic agents, beta blockers, corticosteroids, benzodiazepines, anti-Parkinson’s agents, hormone-altering drugs, stimulants, triptan antimigraine medications, anticonvulsants, proton-pump inhibitors and H2 blockers, statins and other lipid-lowering drugs, and anticholinergic drugs.22 Table 1 lists some medications associated with depression, their reported incidence, and proposed mechanism of action.22

Pharmacotherapy

When treating elderly patients with depression, it is important to remember that although they may respond to therapy as well as younger patients, the time to full response may require up to 8 to 12 weeks. For a first-time depressive episode, treatment for up to 2 years may be required. In patients with 3 or more episodes, lifelong maintenance treatment may be considered. Dosage reduction may lead to relapse; thus dosages to which patients respond should be maintained.2 Currently available antidepressants are listed in Table 2.23,24

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) work by enhancing the action of serotonin by blocking its reuptake at the presynaptic terminals.23 First-line treatment of depression in an elderly patient is generally an SSRI, because of the drug’s fewer side effects, ease of use, and safety (especially in overdose). Time to full patient benefit with an SSRI in the elderly population may be longer than the usual 4 to 6 weeks.25 Despite the more favorable tolerability of SSRIs, some side effects such as Parkinsonism, akathisia, anorexia, sinus bradycardia, and hyponatremia may warrant caution in the elderly population.25 A rare but potentially lethal side effect, serotonin syndrome, may be seen if the patient is taking other drugs that enhance the availability of serotonin.24 One study reported a 2-fold increase in the risk of clinical fragility fracture in patients older than 50 years on a daily SSRI. An increased risk of falling and lower bone mineral density at the hip was also reported in the same group.26 Suicide risk should be monitored in the elderly patient, especially during the first month of treatment. One study found the suicide risk in men older than 66 years of age in their first month of antidepressant therapy to be 5-fold higher with SSRIs than with other antidepressants. No difference in risk, however, was observed in the second month or subsequent months of treatment.27 There is no evidence to show that one SSRI antidepressant is more effective than another and no evidence to show that SSRIs are more effective than older antidepressants.25,28 One SSRI that requires dosage adjustment in the elderly population is citalopram. Due to the risk of QT prolongation with citalopram, the maximum recommended dosage in patients older than 60 years of age is 20 mg daily.29 Citalopram, escitalopram, and sertraline may be preferred due to fewer drug interactions and cognitive effects.30

Serotonin–norepinephrine reuptake inhibitors

Serotonin–norepinephrine reuptake inhibitors (SNRIs) work similarly to the SSRI class, while additionally blocking the reuptake of norepinephrine.23 Adverse effects are similar to the SSRIs but also include sweating, tachycardia, and urinary retention.31 SNRIs should be avoided in patients with uncontrolled hypertension because these agents can cause dose-dependent increases in diastolic blood pressure.32 Similar to SSRIs, SNRIs can cause serotonin syndrome, usually resulting from interactions with monoamine oxidase inhibitors (MAOIs). Examples of drugs with MAOI properties include linezolid, dextromethorphan, sumatriptan, tramadol, and St. John’s Wort.31 Both SSRI and SNRI agents are less lethal in overdose as compared to tricyclic antidepressants.24 Even though the SSRIs and SNRIs are not addictive, it is important to educate patients to avoid abrupt discontinuation of therapy with both classes due to the potential for antidepressant discontinuation syndrome.24 After abrupt cessation, symptoms associated with antidepressant discontinuation usually appear within 2 to 3 days. The medications associated with the highest risk of producing these symptoms are paroxetine and venlafaxine. Sertraline, citalopram, and escitalopram have a lower risk, but the risk with fluoxetine is the lowest.33 An SSRI is usually the drug of choice for patients with late-life depression, but an SNRI is also appropriate first-line treatment.31

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) work by decreasing reuptake of norepinephrine and serotonin.23 TCAs work well as antidepressants; however, their actions at the additional adrenergic, cholinergic, and histaminic receptors produce adverse effects that detract from their overall tolerability in all patients, especially the elderly. These adverse effects include orthostasis, dry mouth, sexual dysfunction, constipation, urinary retention, blurred vision, confusion, and weight gain. Patients often discontinue the medication or are unable to titrate to the highest effective dose of the medication due to the intolerability of the TCAs.24 These agents should be used with caution in patients who have urinary retention, benign prostatic hyperplasia, arrhythmias, cardiac conduction abnormalities, or narrow-angle glaucoma.25 This class of antidepressants is not recommended for first- or second-line treatment in any age group.25 The TCAs still remain an option for patients who do not respond to or cannot tolerate an SSRI or SNRI.31 TCAs, however, are rarely the antidepressant of choice for elderly patients. They should generally be avoided in the elderly population.

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) work by inhibiting monoamine oxidase enzyme, which increases the availability of monoamines causing increased concentration of neurotransmitters such as epinephrine, norepinephrine, and dopamine.23 Adverse effects of this class (sleep disturbance, orthostatic hypotension, sexual dysfunction, weight gain) detract from their use as an antidepressant in the elderly population. Not only are MAOIs associated with a poor adverse-effect profile, they also can cause a potentially fatal interaction with SSRIs, sympathomimetics, and tyramine-rich foods that can cause delirium or hypertensive crisis.24,34 MAOIs are not recommended as a first-line agent for treating late-life depression. Generally, this class is only used when a patient is treatment resistant to other antidepressant agents. Some studies have shown efficacy superior to other antidepressant agents in the treatment of atypical depression, mixed anxiety-depressive states, and panic disorder; however, few studies have included an elderly population of patients.25 Selegiline is available as a transdermal patch, which may provide a convenient dosage form for some elderly patients. An additional benefit with this patch is that when used at its lowest recommended dose (6 mg/24 hr), there appear to be no significant interactions with tyramine-containing foods, as well as fewer sexual dysfunction, weight gain, or hypotensive adverse effects. The absence of these interactions and adverse effects, however, is not seen with higher dosages.31

Other agents

Bupropion

The actions of bupropion with regard to antidepressant activity are not fully understood. It does inhibit the neuronal reuptake of dopamine.23 It may be as effective as the SSRI and TCA classes when treating major depression.35 Patients who suffer with lethargy, fatigue, or daytime sedation may benefit from treatment with bupropion because it is generally an activating medication. It should not be used in patients who have seizure disorders, past or current diagnosis of bulimia nervosa, or are undergoing alcohol detoxification.25 Patients with hypertension should have their blood pressure checked regularly due to the potential for elevation.23 The combination of an SSRI plus bupropion is commonly used.33

Mirtazapine

The chemical structure of mirtazapine is not related to any other antidepressants.23 It has both serotonergic and noradrenergic properties.25 Mirtazapine has an anxiolytic effect and might be beneficial in patients with insomnia, agitation, or restlessness due to its sedating nature. Its sedating effects do tend to diminish with further treatment that includes titration to higher doses.23,25 Its appetite-stimulating effect may prove useful in an anorexic depressed patient.31 Mirtazapine is generally considered a second-line agent.25 Elderly patients should be initiated at lower dosages and titrated more slowly. They are also more susceptible to hyponatremia, a rare side effect of mirtazapine.23 Abrupt withdrawal of mirtazapine should be avoided.

Nefazodone

Nefazodone’s antidepressant activity is due to actions on the serotonergic and noradrenergic systems.23 It is rarely prescribed due to its association with rare, hepatic failure requiring transplantation. Nefazodone has been removed from the market in Canada and Europe because of this serious adverse effect.31 It might be a choice for patients who have insomnia, anxiety, or agitation. It should be used with caution because it is a potent inhibitor of the CYP450-3A4 isoenzyme, which can lead to significant drug–drug interactions.25 In elderly patients, nefazodone should be initiated at half the normal adult dose.23

Trazodone

Trazodone and nefazodone have similar structures.35 Trazodone is rarely prescribed as a sole antidepressant agent but is commonly prescribed as an adjunct to an SSRI in patients with insomnia due to its sedating properties.25,31 Elderly patients usually require a lower dose and may be at increased risk for adverse reactions. If a patient cannot tolerate an SSRI or SNRI, however, trazodone may be preferred over a TCA because it has fewer cardiac effects.23

Atypical antipsychotics

FDA has approved both aripiprazole and quetiapine for the adjunctive treatment of depression. A combination of olanzapine and fluoxetine has been approved for treatment-resistant depression.31 Atypical antipsychotics used as adjunctive treatment for depression in the geriatric population have not been systematically studied. Of concern is the association between atypical antipsychotics and increased mortality in geriatric patients with dementia; however, it is not clear if the low doses used in adjunctive treatment of depression will produce the same association.36

Nonpharmacologic Treatment

Nonpharmacologic therapy continues to have an important role in treating depression. Consensus guidelines for first-line treatment of both mild and severe depression in the elderly population include not only an antidepressant but also psychotherapy.36 Psychotherapy may include cognitive-behavioral therapy, supportive psychotherapy, problem-solving therapy, or interpersonal therapy.35 Increased exercise and exposure to bright light have also shown benefit in the depressed elderly population.25 Electroconvulsive therapy (ECT) can be effective for severe depression. If two trials of antidepressants have failed, ECT becomes a first-line option. ECT is also effective for patients with depression that exhibits psychotic features, who have not responded to antipsychotics and antidepressants.35

Outcomes

The best therapeutic outcome of antidepressant therapy is remission. Nevertheless remission rates for geriatric patients are only approximately 30%. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, only 30% of study participants attained remission status.37 Similarly, other researchers noted that 71% of the 792 geriatric patients with major depression did not achieve remission. Factors increasing nonremission included comorbid anxiety, female sex, general medical comorbidity, and increased baseline depressive symptom severity.38

Depression may affect older patients’ use of medical services such as physician visits and hospital admission rates. In the KORA-Age study, participants with depressed mood had significantly more physician visits than those without depressed mood.39 In the Health in Men Study 44.8% of patients with depressive symptoms had at least 1 emergency hospital admission for nonpsychiatric conditions compared to 22.9% of male patients without depression. In addition, those with depression had longer hospital stays and worse hospital outcomes.40 Depressed patients’ nonadherence to treatment plans are a possible reason for the increased hospital admission rates. Because of their nonadherence, patients may be admitted to the hospital in a more-serious or advanced stage of their condition, which can significantly impact hospital stay durations and health outcomes.

The frequency of antidepressant use in US nursing home residents has increased from 21.9% to 47.5% (1996–2006).41 Investigators have also evaluated antidepressant use for older patients admitted to Veterans Affairs (VA) Community Living Centers during an 18-month period. They identified that 25% of patients potentially underused antidepressants (patients had depression diagnosis but were not receiving an antidepressant), 42% potentially overused antidepressants (patients without depression were taking an antidepressant), and nearly 60% of patients with depression receiving antidepressant therapy had 1 or more prescribing problems (eg, drug–drug and drug–disease interactions). Patients with moderate-to-severe pain and those taking anxiolytic/hypnotic medications were at significantly increased risk for inappropriate use of antidepressants. Patients with mild/moderate cognitive impairment, polypharmacy (>5 medications), cerebrovascular accidents, other anxiety, or taking an antipsychotic without diagnosis of schizophrenia were at greater risk for overuse of antidepressants. The only associated risk factor for antidepressant underuse was activities of daily living (ADL) dependencies.42

Role of Pharmacists

Pharmacists can provide several important services to their older patients with depression. Providing educational information about depression and antidepressant medication could enhance medication adherence. Additionally, monitoring patients for medication effectiveness, side effects, and adherence could improve treatment outcomes. For patients who are not aware of or have not sought medical care for depression, the pharmacist may encourage them to make an appointment with their primary care provider for assessment.43 Researchers have evaluated pharmacists’ perceived barriers to providing depression care and found deficiency in psychiatric education, minimal time for personalized care for patients, limited patient information related to treatment, lack of private spaces in the pharmacy to talk to patients about mental health issues, and concerns about effectively communicating with depressed patients were the most commonly noted barriers.44

In a study evaluating the impact of pharmacist intervention on outcomes of depressed primary care patients, investigators reported significant improvement in antidepressant use rates for intervention patients (57.5% vs 46.2%) and for patients not on antidepressants at enrollment (32.3% vs 10.9%). Pharmacist consultation was either conducted in person or by telephone.45

As the most accessible healthcare provider, pharmacists are in a unique position to inform patients and assist in recognition of depression, offer screening, provide education, and offer support to their elderly patients who may be suffering from depression. Pharmacists can monitor for patients’ somatic complaints that might indicate undiagnosed depression. Pharmacists should be cognizant and able to recognize comorbidities and medications that may contribute to depression in the elderly patient. They can also advocate for their patients to discuss their symptoms with their primary care providers. For those patients receiving medication therapy for depression, pharmacists should be mindful of potential drug–drug and drug–disease interactions as well as side effects, monitor refills to ensure medication adherence, and counsel patients about the possible need for continued maintenance therapy. Pharmacists may also consider innovative practice or outreach opportunities, such as community presentations on the signs and symptoms of depression, developing a call intervention system for elderly patients taking antidepressants, offering medication reviews to determine potential medication causes of depression, offer educational brochures in the pharmacy, or collaborate with primary care providers in the community to provide free screenings.

Because so many elderly are affected by depression and studies have shown depressed elderly have a higher morbidity and mortality with increased use of healthcare resources and costs, pharmacists have a professional duty to ensure they receive optimal pharmacy care in their treatment of depression.

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