Managing Depression in the Elderly: Exploring New Options

It is estimated that among the approximately 1.5 million residents of long-term-care facilities in the United States, 80% to 90% have some psychiatric disorder, and that more than 60% have dementia. Despite ample opportunity to observe nursing home residents, fewer than 25% of depressed patients receive treatment. Furthermore, approximately 40% of patients with depression are not diagnosed even though 30% to 50% of them have significant depressive symptoms and 15% to 25% have major depression. The annual incidence of depression is approximately 13%. Evidence suggests that a first major depressive episode that occurs at age 65 years or after may be a prodrome to subsequent Alzheimer’s disease. Thus the failure to recognize and treat depression effectively may place the patient at increased risk for cognitive and behavioral deterioration.

During this industry-sponsored breakfast symposium, the faculty discussed the assessment and diagnosis of depression in the older population as well as traditional and emerging treatment options.

This program was supported by an unrestricted educational grant from Forest Pharmaceuticals, Inc.

Assessment and Diagnosis of Depression

Jeanne M. Jackson-Siegal, MD (Yale University) noted that one probable reason for commonly overlooking or misdiagnosing depression in the elderly is that the clinical presentation tends to differ from that in younger patients. In place of the characteristic sad demeanor of the younger person, the older depressive patient is more likely to display somatization anxiety or irritability. This frequently leads to improper treatment with benzodiazepine agents. The older depressed patient may have mild memory loss; and if the depression is concurrent with dementia, the memory loss may be further worsened. Although older depressed patients usually deny guilt feelings, they frequently acknowledge regretting that they have become a burden to others, and they may dwell on the horrible feeling of being of no value. Although they typically deny suicidal intentions or fantasies, many admit that death would be a welcome relief. Dr. Jackson-Siegal characterized this tendency as “passive suicidal ideation.”

Depression impairs virtually every aspect of life from the general quality of life and sense of well-being, to social relations and daily activities, to the ability to function. Moreover, there is compelling evidence that depression leads to inferior clinical outcomes of medical illnesses including stroke rehabilitation and cardiac disease morbidity and mortality. Depression also significantly increases risk of mortality, with suicide contributing only a small portion of the overall risk increase. In one study population, for example, depression predicted a 59% increase in mortality during the first year in a skilled nursing facility.

Admission to a nursing home may contribute to depression in elderly individuals because it entails a major disruption in life. This consists of removal from friends and loved ones and adaptation to a new environment of unfamiliar sounds, routines and diet. These, together with loss of financial stability and mobility restrictions, may be interpreted as a loss of autonomy and, in its place, a degree of dependence that diminishes enthusiasm for future goals. A limited vision of future happiness and a growing sense of hopelessness may result.

Effective treatment of depression should improve appetite and nocturnal sleep, enable patients to participate actively in rehabilitation, and reverse negative behavioral manifestations. Too often, however, patients are treated inappropriately. Frequently this consists of benzodiazepine therapy for women and treatment of men with antispychotic agents. These are associated with oversedation resulting in increased risk for falls and orthostasis, daytime somnolence, and other adverse events that diminish the quality of life and participation in activities despite the patient’s apparent tranquility.

The Minimum Data Set (MDS) is an easy and useful instrument for revealing evidence of depressive symptoms. Subsection 1 of Section E outlines the symptoms of functional depression (distress, agitation, withdrawal, thoughts of death, weight loss and waking in an unpleasant mood). This subsection also addresses verbal expressions of distress, sleep-cycle issues, and appearances that may be indicative of depression. Subsections 2 and 3 deal with mood persistence/change. Table 1 outlines other pertinent sections of the MDS. Dr. Jackson-Siegal identified some “common red flags” or indicators of improper medication to which the consultant pharmacist should be alert when reviewing charts: the use of sleep, anxiolytic, pain or bowel medications, and the administration of tranquilizers during the day. While the MDS may provide useful clues, the use of a proper screening instrument is far more helpful. |

Standardized screening for dementia and depression is uncommon in nursing homes in the United States.

“The Mini Mental Status is a 5-minute screening test that may be the most important thing we can urge our long-term-care colleagues to perform routinely,” Dr. Jackson-Siegal said. Based on the outcome of screening, one may wish to proceed with the 15-point Geriatric Depression Scale for more cognitively intact patients or the Cornell Scale for Depression in Dementia. (The Hamilton Depression Rating Scale (HAM-D), the Beck Depression Inventory and the Montgomery-Asberg Depression Rating Scale (MADRS) are valuable in research, but have little application in the nursing home.) The diagnostic criteria for major depression are a depressed mood plus five SIGECAPS symptoms, or loss of interest or pleasure plus four SIGECAPS symptoms. The symptoms must endure for more than 2 weeks and must cause distress or decreased function. The SIGECAPS symptoms are sleep disturbance, interest problems, guilt, energy decrease, concentration decrease, appetite disturbance, psychomotor abnormalities and suicidal thoughts.

In the differential diagnosis of depression, one must consider the environment, dementia, delirium (especially hypoactive delirium), medical illnesses (e.g., hyponatremia, anemia, carcinoma, cerebral vascular accidents, Parkinson’s disease, hypothyroidism, vitamin B12 deficiency, pharmacologic toxicity or interference), frontal lobe impairment (especially in apathetic patients), psychosis and anxiety disorder. Depression is usually differentiated from dementia by higher depression scores and accentuated mood-related symptoms. Depression and anxiety coexist in 90% to 95% of patients with affective disorder. New-onset anxiety in elderly individuals is frequently indicative of depression. Somatization may also increase in these patients. Coexisting anxiety in depressed patients is associated with increased symptom severity, a more chronic disease course, poorer clinical outcomes, increased impairment and a higher suicide rate than with depression alone.

Importantly, anxiolytic agents neither resolve depression nor decrease suicide risk, but they do increase falling risk by inducing ataxia and decreasing central nervous system function. Low-dose trazodone may be an effective replacement for anxiolytics. However, while it induces less cognitive impairment than anxiolytics, it is associated with orthostasis that requires vigilant monitoring to ensure stable blood pressure.

Dr. Jackson-Siegal concluded her presentation by emphasizing the potential benefit of psychotherapy focused on functioning in addition to pharmacologic intervention. This includes individuals with mild dementia. While extremely effective, electroconvulsive therapy is associated with permanent memory loss. Therefore, pharmacotherapy is the mainstay for patients who require intervention.

Table 1. MDS Elements Regarding Symptoms and/or Outcomes of Depression

Section K. Oral/Nutritional Status
  • Subsection 3. Weight change
  • Subsection 4. Nutritional problems
Section N. Activity Pursuit Patterns
  • Subsection 1. Time awake
  • Subsection 2. Average time involved in activities
Section O. Medications
  • Medication use patterns
Section B. Cognitive Patterns
  • Subsection 2. Memory
  • Subsection 4. Cognitive skills for daily decision-making
Section F. Psychosocial Well-being
  • Subsection 2. Unsettled relationship
  • Subsection 3. Past roles

Management of Depression

In the introduction of his presentation on the management of depression, William J. Burke, MD (University of Nebraska) cited the characteristics of the ideal antidepressant: (i) efficacy, (ii) safety, (iii) once-daily dosing with minimal titration, (iv) cost-effectiveness and (v) anxiolytic effects. He emphasized, however, that “when selecting among agents for managing depression, safety rather than efficacy is the primary concern.” The typical nursing home resident has many illnesses, takes many medicines and is highly sensitive to the potential side effects of these agents. Anti-histaminic, anticholinergic and anti-adrenergic drugs can all be extremely problematic in older frail individuals. Although overdosing is not as common a problem in the nursing home as in the community, avoidance of both potential drug/ drug interactions and cardiovascular risk is essential.

With regard to efficacy, multiple clinical studies have demonstrated that in patients with mild to moderate depression, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants are virtually equivalent. SSRIs have been dominant in recent years, however, because of their superior safety profile and their ease of use. Venlafaxine, a potent inhibitor of serotonin and norepinephrine reuptake, has also been used widely in this setting.

A recent development of particular interest in this field is the separation of racemic citalopram into S- and R-enantiomers, its mirror-image stereoisomers that are present in equal amounts in the racemic mixture. Studies indicate that S-enantiomer (referred to as escitalopram) is 167 times more likely to bind at the serotonin receptor than is the R-enantiomer. Consequently, all of the therapeutic effect of racemic citalopram is attributable to its S-enantiomer. Escitalopram was developed specifically to eliminate side effects due to R-citalopram and to clean up the pharmaco- kinetic profile of the parent drug. Studies of the two enantiomers now indicate that escitalopram is the most selective SSRI, and that it is twice as potent as racemic citalopram. In contrast, R-citalopram is not therapeutically active but does have other receptor effects, such as binding at the H1 receptor, that may be associated with adverse side effects and may actually inhibit the activity of the S-enantiomer (Hytel J et al. J Neural Transm Gen Sect 1992;82(2):157; Owens MJ et al. Biol Psychiatry 2001;50(5):345; vonMoltke LL et al. Drug Metab Dispos 2001;29(8):1102). In a placebo-controlled fixed-dose study comparing citalopram 40 mg/day, escitalopram 10 mg/day and escitalopram 20 mg/day for 8 weeks in younger patients, both doses of escitalopram separated significantly from placebo at week 2 and remained separated at every point thereafter as demonstrated in Figure 1 (Burke WJ et al. J Clin Psychiatry 2002;63(4):331).

Pharmacokinetic studies indicate that escitalopram has a half-life of approximately 35 hours, making it a true once-daily medication. In comparison with other leading SSRIs, it is the least protein-bound and thus may be given safely with more tightly-bound compounds. Escitalopram, like citalopram, is dose-related and has linear pharmacokinetics. However, a limited amount of in vivo data suggests that increasing the dose to 20 mg/day may result in 2D6 inhibition similar to that observed in the parent compound. This is apparently insignificant clinically in virtually all patients. One of the attractive features of escitalopam for treating depression in older patients is that it has very little neuronal transmitter activity other than serotonin by virtue of high specificity for the serotonin receptor. Escitalopram is metabolized by three different CYP450 systems. Consequently, even in the presence of an inhibitor of one of the three pathways, accumulation and resultant clinical manifestations are highly unlikely.

Because of this favorable pharmacokinetic profile, escitalopram is well tolerated by frail older patients and may be considered as first-line therapy for mild depression in this population. In a review of all patients 60 years of age and older who received double-blind treatment with escitalopram (n=216) or placebo (N=214) in five short-term trials in which there was no dose adjustment for age, nausea and abdominal pain were the only adverse effects that occurred more frequently than in the placebo group. There were no laboratory abnormalities or changes from baseline in vital signs or body weight, and no clinically notable changes in ECG values (Burke WJ et al. ICGP Proc, 2002. Alphabetic listing at www.IGCP.org under “Poster Abstracts”).

In general, SSRIs are well tolerated, but there are potential side effects that should be considered when selecting among them. For example, activating side effects such as insomnia, tremor and agitation may occur most frequently with fluoxetine. Gastrointestinal side effects, most particularly nausea, are common with all SSRIs. Sertraline may cause more diarrhea while paroxetine may produce constipation. Cardiac side effects are uncommon with these drugs, and are generally limited to slight bradycardia of little clinical significance. Perspiration, and even profound nocturnal perspiration, is not uncommon with SSRIs, and may not occur for 3 or 4 weeks following the initiation of therapy.

Some SSRI side effects occur more frequently in older patients, including apathy and anorexia. Thus, these patients should be monitored for appetite and weight loss during SSRI therapy. SSRI treatment can also cause inappropriate antidiuretic hormone (ADH) secretion, extrapyramidal effects, increased risk for falls and hip fracture, and have been reported to be associated with an increased risk for gastrointestinal bleeding. Because abnormal secretion of ADH may lead to hyponatremia, any change in mental state should lead to a prompt evaluation of serum sodium.

Methylphenidate may be useful for the treatment of depression in individuals newly admitted to the nursing home for physical rehabilitation. Depression frequently prevents individuals from participating vigorously in rehabilitation therapy, and they may risk losing valuable time. The relatively rapid therapeutic response to methylphenidate, typically a few days at starting doses of 1.25 mg/day to 5.0 mg/day titrated to a maximum of 20 mg/day, may offset this problem while antidepressants intended for long-term therapy begin to yield therapeutic benefit. Patients taking this agent should be monitored for heart rate and appetite, as it may induce tachycardia and/or anorexia.

Dr. Burke emphasized that when introducing an antidepressant to a patient, it is important to start at a low dose and to titrate slowly for safety, but it is equally important to titrate sufficiently to reach a clinically effective dose. Patients should always be monitored for evidences of toxicity.

Case Studies

Following the formal presentations, Thomas M. Chamberlain, PharmD, FASCP (Chesapeake, VA), who chaired the symposium, led a discussion of three cases of depression in elderly patients.

The first patient was an 86-year-old widow with a recent (3 months) history of hip fracture and 19-pound weight loss (6 months). She had numerous somatic complaints including pain, along with frequent insomnia and poor compliance with rehabilitation. Her MDS and MMSE were 9 and 22, respectively. In his evaluation, Dr. Burke stressed the importance of ruling out underlying medical causes of weight loss (e.g., anemia, infection, occult malignancy) and of reviewing medications before treating for depression. Dr. Jackson-Siegal suggested that prn medication for pain be replaced by a routine pain-management strategy and that the patient’s insomnia be treated with a medication such as trazodone. Because the mental screening indicated a “pretty miserable state with prominent insomnia,” she suggested treatment with either mitrazapine or an SSRI. Dr. Chamberlain noted that short-term weight loss in depressed patients often reverses during antidepressant therapy, presumably because of improved appetite.

The second case dealt with the management of depression concurrent with Alzheimer’s disease. A 77-year-old unmarried male patient who had been in a nursing home for more than a year had symptoms of agitation, annoyance and uncooperative behavior. His medical history included hypertension, diabetes and obesity. His Cornell and MMSE scores were both 14. Because of the patient’s agitation and Alzheimer’s-related brain fragility, Dr. Jackson-Siegal suggested an antidepressant such as citalopram because it is neutral with respect to psychomotor changes. She recommended continuation of trazodone and the addition of a memory-enhancing medication. Dr. Burke observed that SSRIs are generally effective in improving behavioral disturbance in patients with dementia as well as alleviating depression. He recommended citalopram, escitalopram or sertraline for this patient.

Case III involved a 79-year-old widow admitted to a nursing home for rehabilitation, having suffered a stroke 5 weeks previously and sustained right-sided weakness. She was resistant to rehabilitation and complained of fatigue. Her history included atrial fibrillation, hypertension and dia- betes. Her depression was managed with paroxetine. Dr. Jackson-Siegal noted that although many clinicians use tricyclic antidepressants for managing post-stroke depression, their side-effect profile of confusion, constipation, blurred vision and dry mouth makes it important to avoid them entirely. Of the SSRIs, only citalopram has demonstrated efficacy in a placebo-controlled trial. Both Dr. Jackson-Siegal and Dr. Burke stressed the need to treat the patient sufficiently to start rehabilitation quickly. Failure to act quickly has a significant impact on mortality and morbidity in the first few months following a stroke. In this case, paroxetine may hinder the patient’s capacity to start rehabilitation. Dr. Chamberlain recommended use of an agent of rapid onset of action to accelerate rehabilitation.

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