Evaluation and Treatment of Depression in Patients with Cognitive Impairment

This continuing medical education activity is sponsored by the Johns Hopkins University School of Medicine, Baltimore, Maryland. The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. These examination questions are based on the article “Evaluation and Treatment of Depression in Patients with Cognitive Impairment,” which appears on pages 39-45 in this issue of Clinical Geriatrics.

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The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Credit Designation Statement
The Johns Hopkins University School of Medicine designates this education activity for a maximum of 1.0 category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity.

Valid November 1, 2004 - January 31, 2005.

Estimated time: 1 hour

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As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The presenting faculty reported the following: Dr. Watson has indicated that she has not received financial support for consultation, research or evaluation or has a financial interest relevant to this article. Dr. Steffens has indicated that he has received an honorarium from Forest Laboratories, Inc. No faculty member has indicated that their presentation will include information on off-label products.

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Educational Objectives
1. To recognize signs and symptoms of depression in patients with cognitive impairment
2. To identify key features of the comprehensive depression evaluation in cognitively impaired patients
3. To recognize and recommend appropriate pharmacologic treatments for depression in cognitive impairment
4. To become familiar with standardized screening tools for depression in cognitive impairment
5. To recognize an appropriate threshold for referral to a geriatric psychiatrist Instructions

A certificate of completion will be awarded to physicians completing the posttest and evaluation form. Please complete the following examination answer sheet and mail it with your payment of $10 (write the course number OFP# 55-0615 on your check payable to Johns Hopkins-Office of Funded Programs) to: Johns Hopkins University School of Medicine Office of Funded Programs P.O. Box 64749 Baltimore, MD 21264-4749

You will receive the certificate of completion approximately 6-8 weeks after submitting your materials, and receiving a grade of 70% or higher.   Requests for CME credits must be received within 90 days of the publication date of the issue; void after that date. Please contact the CME office at (410) 614-6152, Fax (410) 614-7315, if you have any questions.
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Clinicians caring for cognitively impaired patients should routinely consider depression as a possible coexisting condition. The link between these two conditions, as well as the compelling prevalence of both, is well elucidated.^1-4  However, the detection and treatment of depression in the context of cognitive impairment can be challenging. A systematic approach will help ensure successful management.

Prevalence and Burden of Suffering

Depending on the setting and what threshold of depressive symptoms is considered significant, the prevalence of depression in dementia ranges from 10-80%.^3,5-7 Depression is independently related to poor outcomes, including greater medical morbidity, increased health services use, functional decline, and death.⁸ Older white males are also the most likely to commit suicide of any demographic group, and importantly, many older persons who complete suicide have seen their primary care provider within the last month before death.⁹ 

Subtypes of Depression

Some experts suggest that there is a distinct depressive syndrome associated with Alzheimer’s disease, typically characterized by fewer and less prominent symptoms than the classic criteria symptoms of major depression.^3,7 Others hypothesize that cerebrovascular disease contributes to depression in late life, and an emerging literature characterizes this “vascular depression” as one of many sequalae from common risk factors such as hypertension, diabetes, hyperlipidemia, and smoking.^10-12 Symptoms include executive dysfunction,¹⁰ which may manifest as an inability to initiate, plan, and sequence events; loss of interest in activities; reduced verbal fluency; and psychomotor slowing. These symptoms overlap with those of dementia and may be difficult to discern.

If patients have no history of previous depressive episodes, sometimes called late-onset depression, their symptoms may be more likely to fall in this range of executive dysfunction. Alternatively, patients with a history of recurrent depression (early-onset) often have symptoms similar to their previous episodes. There is, however, considerable overlap among all depressive subtypes in older adults with cognitive impairment.

Clinically, it is less important to correctly categorize the depression than to recognize significant symptoms. Table I lists common symptoms of depression and how they may present differently in those with cognitive impairment.³

Detection

Cognitive complaints (eg, being forgetful, having poor concentration) are common in depression, even in patients without dementia. Historically known as pseudodementia, this phenomena is now believed to not be fully reversible, but in fact a harbinger of future cognitive impairment when seen in older adults.^1,4,13 In contrast, patients with cognitive impairment often do not complain of classic symptoms of depression (eg, feeling sad, disinterested).

Signs such as irritability and apathy may be more prominent, which can be just as easily attributed to the dementia syndrome. Informal interviewing may not uncover the full picture of possible depression. Routine screening with valid and reliable instruments is the best way to detect an underlying depression; several instruments meet these criteria in the primary care setting.¹⁴ For those with Mini-Mental State Examination (MMSE) scores greater than¹⁵, the Geriatric Depression Scale¹⁵ in both the 15- and 30-item versions shows sensitivities of 80-100%. The 15-item version retains as much validity as the longer version and can be easily administered in its “yes/no” format; a score of greater than 5 is considered worrisome for depression. This scale is in the public domain.

Additionally, the Cornell Scale for Depression in Dementia¹⁶ was designed specifically for use in dementia to include caregivers in the evaluation. It is a 19-item, rater-completed instrument that taps multiple important domains including physical signs and diurnal patterns.¹⁶ Also easy to administer, a score of 7 or more has been shown to correlate with serious depression.^17,18  

Work-Up

Once detected by a positive screening test, a more in-depth evaluation for depression should be completed (Table II). It is important to gather information not only about other possible medical illnesses but also about recent changes in the patient’s personal relationships, perceived social support, and community or church involvement. The answers to these questions will point to the severity of dysfunction caused by the depressive symptoms.

Many individuals with mild-to-moderate dementia continue to enjoy active social lives, so a decline in this ability further supports a depression diagnosis. Clinicians should keep in mind that those who rarely had any social interests are not likely to suddenly develop them late in life, so the key is to appreciate the person’s baseline functioning. It is also important to specifically address the issue of suicidality, asking about thoughts, intentions, and any potential plan.

Caregivers

As patients become cognitively impaired, it is common for clinicians to rely on caregivers to offer historical information and to sometimes serve as a voice for the patient. These proxy reports are invaluable in gauging the patient’s day-to-day functioning and his or her progress or decline with regard to management. However, evidence suggests that caregivers may not initially recognize depressive symptoms, sometimes because of their own depression.19-23 This again raises the importance of using structured, objective screening measures to detect depression. Clinicians must also be cognizant of the potential impairment of caregivers, especially elderly spouses who themselves may suffer from depression or dementia.

Treatment

The approach to treating depression in those with cognitive impairment is similar to depression treatment in any older adult. Clinicians must be vigilant to consider medical issues, potential drug interactions, possible side effects, and drug costs.

Few studies have been performed directly targeting depression in patients with coexisting cognitive impairment. One recent report showed that sertraline was more efficacious than placebo in reducing symptoms of major depression in those outpatients with probable Alzheimer’s disease; 84% of those receiving flexible-dose sertraline versus 35% of those receiving placebo showed either partial or full remission of depression.²⁴ Patients in the treatment group were also noted to have fewer declines in activities of daily living (ADL) function and fewer episodes of behavioral disturbance over time.

Previous studies have shown mixed results but have had varying definitions for depression, dementia, and treatment response, as well as limited use of the newest antidepressants.²⁵ There have been no studies examining depression as defined by the newly proposed criteria for depression in Alzheimer’s disease,³ nor any studies addressing depressive symptoms in other forms of dementia.

Although more work remains to be done, the cumulative body of work for late-life depression suggests that patients with cognitive impairment and depression can be successfully treated with antidepressants.⁸  The choice of antidepressant should be individualized based on the most prominent symptoms and potential side-effect profile (Table III). In general, clinicians can begin with a selective serotonin reuptake inhibitor (SSRI) at a low dose, but should assertively increase this dose every week to the maximum tolerated level for a sustained trial of at least 8 weeks. If there has been no response at all by 4 weeks, a switch in medications is indicated.

For patients with weight loss and sleep problems, mirtazapine may be a good first choice. Alternatively, for those who are slowed down with adequate sleep, bupropion may be more activating. Tricyclic anti- depressants should be avoided as first-line agents given the risk of anticholinergic side effects, which may be particularly problematic in patients with dementia. Because most newer antidepressants are metabolized in the liver, caution should be used if there is any hepatic impairment, with attention to potential drug interactions. Many antidepressants also come in liquid or soluble form, making them easier to take if patients have difficulty swallowing pills.

If a switch is indicated, it is most efficient to try a medication from a different class (eg, first sertraline, and if no response, then venlafaxine). If improvement remains limited after two trials for 8 weeks each, referral to a psychiatrist (geriatric psychiatrist, if available) is indicated. Assuming there is a remission of symptoms, antidepressant therapy should be continued for at least one year at the dose that achieved remission. If the patient has had more than one episode of depression, lifelong therapy should be considered.²⁶ 

Nonpharmacologic interventions, including multiple forms of psychotherapy, have proven successful in older adults without dementia who have depression.^27,28 A recent study also showed that exercise and behavioral management can reduce depressive symptoms in patients with Alzheimer’s dementia.²⁹ The level of cognitive impairment would determine the appropriateness of the talk-based therapies, and—whether alone or in combination with antidepressants—the use of any nonpharmacologic therapies would likely exceed the time constraints of the primary care setting and be a point of referral to a mental health provider.

A cornerstone of treatment must include an assessment of the patient’s current psychosocial situation. The fact that a patient has been diagnosed with cognitive impairment is itself a stressor and risk factor for depression. Did he or she also recently lose a spouse? Move from a lifelong home? Become too frail to attend church? Accommodating individual needs and preferences will help establish a therapeutic alliance and can lay the groundwork for a more rapid response to any type of treatment. Such interventions can be as simple as a referral to a social worker who is familiar with aging resources, such as bereavement support groups or transportation services.

Clinicians should also be attuned to the needs of caregivers, as their stress immediately impacts any potential gains for the patient. As is the case with geriatrics, a family approach will likely be the most successful. When initiating treatment, clinicians should educate patients and families about the nature of depression, the normal feelings of stigma, and the expected latency in treatment response.

Other Considerations

The spectrum of dementia severity varies dramatically, and depression may manifest differently based on the level of impairment. Data show that depression is more common early in the dementia process and again later on when dementia symptoms are most severe and often associated with agitation.^18,30 Although depression is common in all stages of dementia, clinicians should be particularly sensitive to the possibility of depression during these times.

Conclusion

Depression is common in patients with cognitive impairment and may not be obvious in the routine clinical encounter. Symptoms such as irritability, multiple physical complaints, or inability to show pleasure may be more prominent than complaints of feeling sad or depressed. Family members also may not recognize signs of depression. Routine structured screening using the Geriatric Depression Scale or the Cornell Scale for Depression in Dementia can detect possible depression.

Further work-up should include a review of current stressors and coexisting conditions that make depression more likely; previous research suggests that when patients perceive high levels of social support they are less likely to be depressed.^31,32 Data are emerging showing that antidepressants can be safe and effective in those with cognitive impairment when titrated to their optimal dose. A common mistake is not using an adequate dose, which should be maintained for at least 8 weeks before declaring treatment failure. For those patients who prefer not to take antidepressants or are not candidates, alternative forms of treatment also hold promise, including psychotherapy and exercise.

Depression and cognitive impairment go hand-in-hand; the presence of one should always trigger a routine search for and treatment of the other. The complexities of this interaction are unfolding, and burgeoning research in this important area promises to deliver more answers in the near future.