Highlights:

• Unique features of depression in the elderly.
• Keys to picking up the diagnosis.
• Pharmacologic treatment.
• When to recommend referral.

Q: What is the best screening tool for assessing depression in elderly patients? A:The Geriatric Depression Scale is the most widely validated screening tool. The questionnaire has been reduced to a single question that is as sensitive and as specific as the 15-item shortened form of the original 30-item scale. The question is: “How often do you feel sad or depressed?” This is certainly something that is easy to ask in the course of a general physical examination or routine office visit. Q:Some patients don’t admit to being sad or depressed. Instead, they report feelings of exhaustion or other somatic symptoms. What are the tricks to reading between the lines and spotting depression in such patients? A:Asking patients if they feel “anxious” or if their “nerves are bad” will often uncover depression, because anxiety is a very common feature of depression in elderly persons. Find out about diurnal variation in symptoms by asking patients what time of day they feel the most exhausted or tired or have symptoms such as pain. Patients who are depressed often say that they feel worst in the morning and better as the day progresses. In contrast, patients who have chronic diseases tend to feel more exhausted and fatigued as the day wears on. Q:How do the symptoms of depression in elderly persons differ from those in younger ones? A:In many ways, the most prominent features of depression in the elderly are unique to this age group (Table 1). Once you determine the severity of these symptoms, you can better establish therapeutic goals and select the most appropriate treatment:

• Vegetative components. These include poor appetite and poor sleep. Unlike younger patients with depression, who sometimes increase their food intake, depressed older persons tend to manifest anorexia and weight loss. The weight loss is often attributed to other medical conditions instead of serving as a prompt to ask about depression. Particularly in patients who have been obese, rapid weight loss resulting from depression may lead to unrecognized protein malnutrition and related complications that present as physical illness. Sleep patterns vary in older persons with depression, but early morning awakening is common. Some patients also complain of nocturia, but they may in fact be getting up to go to the bathroom because they are awake, rather than awakening because of the urge to urinate.
• Multiple somatic complaints. Elderly depressed patients may complain of pain everywhere in the body. Try to tease out which pain is related to an underlying medical condition and which might be related to depression. Pain is exacerbated by depression and tends not to fit easily into a single diagnostic picture. For example, a patient with angina who is going to undergo coronary artery bypass surgery has pain that is obviously related to a medical condition, but the pain may be exacerbated if the patient is also depressed. Painful conditions often improve with antidepressant therapy, which suggests that the state of reduced neurotransmitter levels associated with depression is also part of the pathophysiology of pain. Antidepressants increase the nerve transmitter levels that help suppress pain perception. For example, patients with shingles often become depressed. It may be difficult to determine whether the depression is related to shingles or whether the pain of shingles is exacerbated by depression.
• Psychological symptoms. These may involve obsessive feelings of guilt and worry or rumination during the night. Some patients review all of the things they’ve ever done wrong and may feel that they’re a burden to their families.Ask such patients whether they wish to die or have made plans to take their life. A patient who has developed a specific plan for suicide is in a critical situation. Urgent referral to a psychiatrist is warranted for consideration of electroconvulsive therapy or initiation of antidepressant medication with careful follow-up to ensure that treatment is effective. Some depressed patients also complain of memory problems; this is because their ability to concentrate is impaired by the depression. A high index of suspicion is crucial when a patient complains of memory problems but is obviously depressed— for example, if he or she frequently answers “I don’t know” to questions on cognitive screening tests. In contrast, patients with underlying dementia generally do not complain of—and may deny—memory problems. More often, it is their families who raise the question of memory impairment. During memory testing, patients with dementia either give the wrong answer or look to a family member for the correct one.
• Psychomotor changes. Some depressed older patients appear to have “slowed down,” which is a typical finding in depressed younger persons. When asked, however, older patients often complain about their “nerves” or report feeling anxious. Many manifest signs of agitation. These psychomotor changes may be mistaken for an anxiety disorder, and a benzodiazepine or other sedative may be inappropriately prescribed. Even though anxiety is a very common feature of depression, it is the depression, not the anxiety, that requires treatment. The anxiety will resolve with appropriate antidepressant therapy.
• Diurnal variation in symptoms. The single most important question to ask a patient with suspected depression is how he feels in the morning. If a patient reports that morning is the worst time and that it takes hours to get going, you can be sure he is depressed. Unlike patients with arthritis, whose stiffness dissipates during the first few hours, patients with depression report that their overall sense of wellbeing is worst in the morning. Occasionally, a patient reports that he feels worse later in the day, and some feel afraid to be alone at night. Part of the challenge of diagnosing depression in the elderly is to be aware that depression presents a little differently in this group and to be able to differentiate which patient is reacting normally to life events and which patient is depressed. Although grief reactions to the multiple losses of late life may occur frequently, suspect depression if a patient’s symptoms result in functional decline that persists longer than 2 to 3 months after a significant loss. With the features I’ve outlined above, it is a fairly straightforward process to diagnose depression and prescribe the appropriate treatment.

Q:Which features help distinguish a true anxiety disorder from anxiety that is really a manifestation of depression? A:Anxiety disorders typically have their onset in early adulthood. Although generalized anxiety disorder may occur in up to 5% of community-dwelling older adults, these persons usually have a history of anxiety that began in their 20s or 30s. Thus, an older person with anxiety of recent onset and no history of previous anxiety is more likely to be depressed. Consider a diagnosis of agoraphobia in an older person with anxiety of recent onset who is not depressed. It is crucial to distinguish an anxiety disorder from depression- associated anxiety. Serious complications, such as cognitive dysfunction, fall-related injuries, and worsening of depressive symptoms, can result if a benzodiazepine is mistakenly prescribed for a depressed patient. Q:Many of my elderly patients believe that depression is a normal part of the aging process. Does aging itself cause depression, or are exogenous factors, such as bereavement, the cause? A:We infer that depression in older persons is much more likely to have a biological basis than in younger ones, simply because antidepressant pharmacotherapy is so effective in these patients. About 70% of elderly patients respond to the first drug prescribed, and about 90% respond to a second agent if the first wasn’t beneficial. One hypothesis for a biological basis is that elderly persons are at greater risk for depression because of age-related neuronal dropout, which results in a loss of the brain’s reserve capacity to deal with stressful situations—precisely at the time when the number of stressful situations increases because of bereavement and other traumas. Even so, depression— like cognitive dysfunction—should never be considered a “normal” part of the aging process. Depression is always a medical diagnosis and is usually treatable. I’ve observed that elderly persons who have experienced extreme traumatic events early in their lifetime—such as war or incarceration in a concentration camp—and who seem to have been able to cope with them very well may in later years have a diminished ability to cope with additional psychological stresses, even though these may not be as severe. Exogenous factors undoubtedly play a key role in depression at any age, but as is the case with many bodily systems, our reserve capacity to cope with stress is diminished with age. Q:Other than age, what are the major risk factors for depression in the elderly? A:Chronic diseases, especially chronic pain syndromes, are often associated with depression (Table 2). Acute illnesses or disorders that have a sudden onset and that result in significant disability may also lead to depression. Surgery (even if uncomplicated) can be stressful enough to precipitate a depression; this is a common phenomenon in older patients who have undergone a coronary artery bypass procedure. Undiagnosed depression—which may underlie other medical conditions—is the most common cause of hospital readmission in elderly patients. Q:Which pharmacotherapeutic agents are most effective in elderly persons? What are the specific pitfalls associated with these agents? A:The selective serotonin reuptake inhibitors (SSRIs) are first-line therapy for depression in the elderly; these agents also relieve depression-related anxiety. They are considered first-choice agents because they have a better safety profile than the tricyclics—for example, they are associated with fewer cardiac side effects. Nevertheless, SSRIs are not associated with a reduced incidence of falls compared with the older agents. The SSRIs have a somewhat quicker onset of action than the tricyclics; however, it still takes 2 to 3 weeks to begin to see improvement. Tricyclic antidepressants, such as nortriptyline(Drug information on nortriptyline), may be helpful in a very anxious depressed patient, particularly one with insomnia. Even though SSRIs have become the therapy of choice, recent studies have shown that nortriptyline can be as effective for depression in older persons.^1-3 Fluoxetine(Drug information on fluoxetine) is best prescribed with caution in elderly patients, primarily because of its very long half-life. This can be problematic if delirium or another acute illness develops. Moreover, the risk of extrapyramidal side effects may be increased with a rapiddose titration of fluoxetine. The “start low and go slow” recommendation absolutely applies to the SSRIs. I recommend initiating therapy at half of the usual starting dose. The dose should not be titrated up from this level more often than every couple of weeks; thereafter, it can be titrated monthly until a therapeutic dose is achieved. Q:Which SSRI adverse effects are most troublesome in the elderly? A:Extrapyramidal side effects—including akathisia and Parkinsonian-type symptoms—are sometimes not recognized as side effects of SSRIs and may be confused with persistent symptoms of depression; this can lead to inappropriate dosage escalation. Some patients experience GI side effects, including constipation, diarrhea, or stomach upset. These can be avoided by starting therapy at low doses. Vivid dreams may be a dose-limiting side effect. The potential for drug interactions exists, but this does not generally occur at the lower doses recommended. Generally, the SSRIs are very easy to use. Ironically, this is why it can be difficult to judge how well a patient is doing. Sometimes we assume that as long as a patient is not having side effects, his depression is being effectively treated— but this isn’t always true. That’s why I recommend using the 5 features outlined above (see Table 1) to determine if the patient is making progress and to ascertain that his symptoms have been fully treated. Q:If a patient is having difficulty tolerating a particular antidepressant, should I encourage him to try it for a bit longer, or is a switch to a new drug a better option? A:If a patient whose depression appears to have responded to an antidepressant is clearly having unacceptable side effects, the first step is to reduce the dose. I don’t like to discontinue an agent that seems effective if the problem is simply too high a dose. On the other hand, if a patient is not deriving any benefit from a medication, a switch to a different SSRI is in order. You can usually tell after about an 8- week trial of a drug—if you’ve titrated it properly—whether the patient is improving. This is a subjective evaluation. It is helpful to document the patient’s presenting symptoms under each of the 5 categories listed above and to use that as a guide for follow-up questioning. Q:What is your next step when a patient’s depression does not seem to be responding to a particular SSRI, even if there are no adverse effects? A:I first try another SSRI. Enough of these agents are now available that there are often several from which to choose based on the patient’s symptom profile. It’s a good idea to prescribe a limited number of SSRIs initially so that you become very familiar with the effectiveness and potential side effects of each one. This familiarity will be useful when a significant dose escalation is required. Newer drugs can be used as second-line agents to facilitate familiarity with them as they become available. Q:Which SSRIs might you recommend in specific settings? A:Fluvoxamine, which is available in generic form, is particularly effective in elderly patients who need energy during the daytime but who aren’t sleeping at night. Drug interactions with this agent have not been an issue at doses up to 100 mg. However, if drug interactions are a concern, venlafaxine is a good alternative. I have achieved good therapeutic effect with many of the other SSRIs, which I use according to the labeling and data reported in the literature. Q:What is the optimal follow-up time for a patient whose depression has responded to medication? A:It’s a good idea to see such patients every 6 months. Always encourage patients to make an appointment sooner if they have any questions or problems. Particularly if they have any concerns about side effects and are considering discontinuing their medication, encourage them to call you first. If their condition has been stable with a particular dose of an antidepressant, chances are the “side effect” is related to a different medication or to an intercurrent illness. When patients become ill, they may consider their antidepressant to be the most expendable medication. Be sure to reinforce the idea that the antidepressant is effective only if taken exactly as prescribed. Q:If a patient has had a good response to a medication at a maintenance dosage, how long should I wait to taper the dosage? A:With a depression of recent onset and with a firsttime diagnosis of depression, older patients should generally be treated for 1 to 2 years (depending on the severity of the depression and the response to treatment), because of the increased risk of recurrence. For a trial of drug withdrawal, a gradual taper is recommended. If the depression recurs during the taper, the patient will probably need to take the medication at the established therapeutic dose for life. Q:For which patients should I consider psychiatric referral? A:Depending on the perceived urgency of treatment and on your own comfort level with higher doses, referral to a geropsychiatrist may be considered, especially if the depression has not responded to a second SSRI. One of the most common reasons for lack of therapeutic effectiveness is insufficiently high doses. Also consider consultation if your patient has had only a partial response to therapy; that is, if his symptoms persist, but to a lesser degree, or if he has frequent episodes of recurrent symptoms. Certainly, urgent referral is warranted in any patient with suicidal ideation. It is inappropriate to continue with a drug if its effect is suboptimal—especially since there are so many pharma-cotherapeutic options. It is much more complicated in the long run to manage patients who have been undertreated or partially treated. Q:Some of my patients are uncomfortable with the idea of taking an antidepressant. Is psychotherapy an effective option in this setting? A:I often refer such patients to a licensed clinical social worker or other professional who can provide psychotherapy. Many patients do benefit, even those who have mild cognitive impairment. Often, the decision to undergo psychotherapy is based on cost and convenience considerations. Patients can also seek counseling from a member of the clergy or become involved in group programs or other informal activities. Some patients’ families give them all the support they need, and this can be a key factor in overcoming a depressive illness. Some older patients may resist taking antidepressants because they grew up in a time when psychiatric illness was a major stigma. Some patients may be more receptive to psychotherapy or may have mild depression that responds very well to this type of therapy. The decision whether to use antidepressants, psychotherapy, or a combination of the two depends on the severity of the depression, the patient’s response to a single modality, and practical considerations. Q:Would you comment on the use of St John’s wort? A:The results of clinical trials of St John’s wort have been ambiguous. Although this herb may be useful for mild to moderate depression, recent trials (including one conducted by the NIH) suggest that St John’s wort is ineffective in treating a major depression of moderate severity.4 Side effects of St John’s wort include dry mouth, dizziness, GI symptoms, increased sensitivity to sunlight, and fatigue. This agent may also have adverse interactions with other drugs or reduce their effectiveness. Because complementary medicines are not held to the same FDA standards as prescription or overthe- counter agents, the contents may not correspond exactly to statements on the label. There may also be significant batch-to-batch discrepancies in chemical composition and quality, even in a single product from the same manufacturer. Be sure to encourage patients to inform you of any alternative or complementary products they may be taking so that the potential for side effects and drug interactions can be minimized.