A 75-Year-Old Man With Depression

DR BURNS: Mr S is a 75-year-old man who has had depressive symptoms for the past few years. He is married with 3 adult children and several grandchildren. He has managed Medicare insurance.

Mr S has no prior history of depression. He first began having difficulties with depression about 2½ years ago following coronary artery bypass graft surgery, followed by an ablation procedure for persistent atrial fibrillation. Initially, the procedure was successful, but his rhythm later reverted to atrial fibrillation. His past medical history is otherwise noteworthy for hypertension, hyperlipidemia, benign prostatic hyperplasia, and seizure disorder (he had his last seizure in his 30s).

About 2 years ago, Dr W referred Mr S to a psychiatrist for depressive symptoms. Mr S started taking venlafaxine XR (75 mg/d) with improvement in his symptoms. In April 2001, his depression worsened. His dose of venlafaxine XR was increased to 112.5 mg, and he was referred to a social worker. At that time, Mr S acknowledged lack of energy, lack of interest in pursuing usual pleasurable activities, social withdrawal from family activities, loss of appetite (with a 10-lb weight loss over 6 months), and hypersomnia. His symptoms improved with the higher dose of venlafaxine, and he chose to curtail follow-up with his social worker.

Mr S retired about 10 years ago and states that he never adjusted well to retirement. He also notes concern about the medical problems that his older brothers have faced: one has Alzheimer disease and the other has multiple medical problems.

His current medications include atorvastatin, digoxin, diltiazem, venlafaxine, furosemide, terazosin, mephobarbital, primidone, and warfarin. He has no known drug allergies. A thyrotropin (TSH) measurement within the past 6 months was normal.

Mr S and his wife wonder whether he should continue to receive medication to treat his depression, at what dose, and for how long.

As I look back on it, I think part of my problem is that I really did not prepare for retirement very well, or at all. I've slowed down—I've probably been slowing down for years, but I was never aware of it.

I had the operation, the bypass. I think I was 72 at the time, in perfectly good health and then something major happens. It comes as a shock. The symptoms of depression were more apparent to others around me than they were to me. I think I realized that something was wrong after the fact. The symptoms were that I just couldn't get up and get going and do anything. I slept a lot, and just moped around a lot.

The treatment was mainly medication. I could see some improvement, but it seems that I would have swings of improvement and falling back. So, the medication was increased and that seems to be working very well now.

Sometimes I get into periods of thinking about a particular episode in my life or a problem I had to deal with. But generally, I try to look outward rather than inward.

Within the prior 6 months, he had gone through a pretty complicated and stormy series of medical problems, which he was weathering very well—at least physically. He had lost interest in his usual activities. He had trouble concentrating. He had lost his appetite. He was sleeping more than usual. So, he had developed a number of symptoms, but he did not actually recognize himself to be depressed. As I recall, he came in and said, "The people around me are concerned about me because I'm not acting as they think that I should." At that point, it was clear that he was wrestling with depression.

Given the complexity of his medical regimen, I wasn't sure what would be the best antidepressant. I was able to arrange to have him seen that week by a psychiatrist who recommended starting him on venlafaxine. Over a period of months, Mr S returned, not quite to his former self, but he was clearly much better than he had been.

We are now considering what we should do with his antidepressant medication—whether this is something that we should continue for years to come, or life long, or whether we should think about stopping it at some point. He reads about how depression puts him at an increased risk for mortality, especially with coronary disease. To what extent is that true? To what extent does treatment with antidepressants reduce that risk? Is there anything else that we can do specifically to reduce that risk?

What is the prevalence and natural history of depression in the elderly? How often is depression seen in elderly patients with no prior history of mental health issues? What is the differential diagnosis for new or worsening depression in an elderly patient? What overall evaluation should the primary care physician undertake? How do you distinguish normal grief from depression? How do you differentiate depression from dementia? What should be the role of the primary care physician in treating depression in elderly patients? How effective are nonpharmacologic therapeutic interventions in this population? How do you discuss this diagnosis with the patient? When do you involve the patient's family? What do you recommend for Mr S?

DR KROENKE: Mr S developed major depression following the onset of atrial fibrillation, coronary artery bypass graft surgery with subsequent complications, and failed attempts at radioablation. Apparently, this was his first known episode of major depression. His family was actually more aware than Mr S that something was wrong, and they encouraged him to see his primary physician. He had experienced loss of interest in his usual activities, fatigue, decreased concentration and appetite, and excessive sleeping. When explicitly asked, he acknowledged feeling depressed but denied suicidal thoughts or plans. Because of his complicated cardiac condition and his multiple medications, his primary physician immediately referred him to a psychiatrist. Mr S initially responded well to low doses of an antidepressant, but required a dosage increase when the stresses of moving to a different home triggered a relapse of his depressive symptoms. Mr S's depression has been in remission now for more than a year, and both he and his primary physician wonder about reducing or discontinuing his antidepressant medication.

Nearly 5 million of the 31 million Americans older than 65 years experience clinically significant depressive syndromes.¹ Major depression is present in at least 5% or more of older adult patients seen in primary care, and less severe forms of clinical depression (dysthymia and minor depression) exist in at least another 10%.^{1 - 2} Article summarizes the diagnostic criteria for these common depressive disorders. Depression is associated with disability, diminished quality of life, and health care costs equal to or exceeding many medical disorders.^{3 - 5} Depressive disorders are at least 2 to 3 times more common in hospitalized patients, nursing home residents, or outpatients with chronic medical disorders. In particular, the 3 C's—cardiovascular disease, central nervous system disorders (eg, strokes, dementia, Parkinson disease), and cancer—are medical conditions prevalent in the elderly and associated with a high risk for coexisting depression.⁶ Mr S's cardiac bypass surgery and subsequent complicated course are quite likely what triggered his major depressive episode. In some older individuals, depression may also be precipitated by psychosocial factors such as bereavement, social isolation, financial constraints, and being a caregiver for a significant other with serious medical problems or cognitive impairment.¹

SYMPTOMS ["SPACE DIGS"]
Less Depression-Specific Symptoms
Sleep disturbance (either insomnia or hypersomnia)
Psychomotor retardation or agitation
Appetite disturbance (decreased or increased) or weight loss or gain
Concentration difficulties
Energy low (ie, tiredness, fatigue)
More Depression-Specific Symptoms
Depressed mood
Interest in activities is diminished or lost (ie, anhedonia)
Guilt or feelings or worthlessness—excessive or inappropriate
Suicidal ideation or thoughts of death

DIAGNOSTIC CRITERIA
Major Depression. At least 5 of the 9 DSM-IV symptoms have been present nearly every day for 2 or more weeks, and at least 1 of the symptoms is depressed mood or anhedonia.
Dysthymia. Depressed mood plus at least 2 additional DSM-IV symptoms have been present more days than not for at least 2 years.
Minor Depression. Individual does not meet criteria for major depression or dysthymia but does have 2 to 4 depressive symptoms that have been present nearly every day for at least 2 weeks, and at least 1 of the symptoms is depressed mood or anhedonia. [Although not yet an official DSM-IV diagnosis, minor depression has been proposed as a mood disorder.]
(For more details see Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Washington, DC: American Psychiatric Association; 1994.)

Older adults may be at greater risk for chronicity of depression than younger persons.¹ A meta-analysis of outcomes in depressed older adults estimated that at 2-year follow-up, 33% of subjects were well, 33% remained depressed, and 21% had died.⁷ Comorbid medical illnesses, disability, cognitive impairment, and more severe depression predicted a worse prognosis. Depression decreases compliance with medical treatment, which can be particularly problematic in older persons with multiple medical illnesses being treated with numerous medications.⁸ Depression is also associated with an increased risk of mortality in hospitalized elderly patients following discharge, nursing home residents, and persons with certain chronic medical disorders, such as cardiovascular disease.^{1 ,9 - 11}

Dementia, bereavement, and depression secondary to a medical disorder or medication are important conditions to consider in evaluating an older person with depression. While "pseudodementia" (ie, depression masquerading as dementia) can occur, depression and dementia often are comorbid conditions rather than one mimicking the other.^{12 - 13} There is preliminary evidence that late-life depression with cognitive impairment that is reversed by antidepressant treatment may be a predictor of the development of Alzheimer disease or vascular dementia in some patients,¹² although the evidence is not yet conclusive.¹³ Also, executive (prefrontal) dysfunction on neuropsychological testing (ie, disturbances in planning, organizing, and abstracting) and white matter or subcortical gray matter abnormalities on neuroimaging have been associated with an increased prevalence of late-onset depression.^{14 - 16} Executive dysfunction may also predict a poor or delayed response to antidepressant therapy or a greater risk of relapse after discontinuing treatment, while the prognostic significance of neuroimaging abnormalities is not yet clearly established.^{16 - 17} One of the 9 criteria for depression is difficulty with memory or concentration, a cardinal feature of dementia. However, other symptoms such as depressed mood, anhedonia, sleep disturbances, appetite changes, and guilt or worthlessness suggest that depression is either the primary or at least a coexisting condition. Dementia, on the other hand, produces objectively demonstrable cognitive impairment. Also, a more rapid onset and, of course, a therapeutic response to antidepressants favors the diagnosis of depression. If in doubt, an empiric treatment trial is usually warranted.^{18 - 19} Mr S did notice some difficulty in concentrating, but the onset was relatively acute, coinciding with his other depressive symptoms, and resolved with antidepressant treatment.

Grief following the death of a loved one can also produce the symptoms of a major depressive episode. Each year, 800 000 Americans lose their spouse, leaving 11 million widows and 2 million widowers, a total of 7% of the population.¹ A third of those who lose a spouse meet criteria for major depression in the first month after the death, and half of these remain clinically depressed 1 year later.²⁰ However, substantial improvement should occur within 2 months, and those who continue to meet criteria for major depression after this time period should receive antidepressant or nonpharmacological depression therapies. Treatment should be initiated earlier than this in patients with suicidal ideation, severe functional impairment, a prior history of depression, or other signs of a severe depression.

True secondary depression—that which is due to the biological effects of medical diseases or medications—is far less common than depression simply coexisting at higher rates with chronic physical illnesses, known as medical comorbidity.⁶ Glucocorticoid excess, either endogenously as seen with Cushing disease or, more commonly, when prescribed for various medical conditions, can produce mood disturbances in some patients. Although hypothyroidism (and occasionally hyperthyroidism) is purported to cause depression, the evidence is mostly from uncontrolled studies with small numbers of patients.²¹ In the IMPACT (Improving Mood: Providing Access to Collaborative Treatment) study, a treatment trial of late-life depression, a TSH value of 10 µU/L or greater was found in only 0.7% of 726 elderly patients with clinical depression, similar to rates in an elderly population in general.²²

While lists of medications that might cause depression are long, the actual incidence of clinical depression associated with such drugs is not well known. For example, conventional wisdom suggested that β-blockers might cause depression in an important minority of patients, but studies controlling for confounders did not show this to be the case.²³ While certain somatic symptoms such as fatigue might be adverse effects from medications, this is less likely for cognitive symptoms such as depressed mood, anhedonia, and feelings of guilt or worthlessness. Also, the absence of a clear temporal relationship (ie, onset of symptoms shortly after initiating the medication) makes a medication-induced depression less likely. Rather than medications causing the depression, more important concerns related to polypharmacy often seen in depressed elderly patients are increased noncompliance, drug-drug interactions, and pharmacy costs. None of Mr S's medications has been established as a cause of secondary depression, with the possible exception of mephobarbital. Since he has been taking this anticonvulsant for several decades, however, it is unlikely to be the cause of his depression and discontinuing it would not be recommended. Finally, some feel that the distinction of primary vs secondary depression is an arbitrary dichotomy and that depressive syndromes may be the "final common pathway" of a number of psychological and physiological processes that coexist. For example, Mr S's depression may well be due to both the psychological effects of his medical illness stressors (and their effects on functioning and perhaps on family relationships) and the effects of his cardiovascular disease and subsequent complications.

Depression is a clinical diagnosis based entirely on an adequate patient interview. There are no findings on physical examination or laboratory testing that confirm the diagnosis; the latter is primarily of value in evaluating medical disorders that commonly coexist with depression and to rule out uncommon causes of secondary depression in selected patients. A patient must acknowledge at least 5 of 9 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) symptoms nearly every day for 2 or more weeks to meet criteria for major depression, and one of these symptoms must be depressed mood or anhedonia ( Article ).²⁴ Indeed, simply inquiring about recent depressed mood or anhedonia will detect 90% to 95% of patients with major depression and has a sensitivity similar to much longer depression questionnaires.^{24 - 25} Mr S had problems with sleep, appetite, concentration, low energy, and anhedonia for the requisite time period, thus meeting the criteria for major depression. As is often the case with a first episode, the depression was even more apparent to family members than Mr S himself.

Four DSM-IV symptoms in particular require consideration of medical causes: fatigue, appetite or weight changes, disordered sleep, and impaired concentration. However, most older persons with clinical depression will also have at least 1 or more depression-specific symptoms such as depressed mood, anhedonia, feelings of guilt or worthlessness, or thoughts of death. It has not been established that geriatric-specific depression questionnaires or different symptom criteria are required in older patients.^{13 ,24 - 26}

Since depression is frequently a recurrent or chronic disorder, asking about a past history of depression as well as the efficacy of any previous treatments is valuable from both a diagnostic and management standpoint. The neurological part of the physical examination is particularly important to evaluate for central nervous system disorders that occasionally mimic but more commonly coexist with depression, such as dementia, stroke, and Parkinson disease. While there have been reports of objective abnormalities on neuroimaging, cerebral perfusion, and sleep studies, a causal relationship has yet to be established.²⁷ Whether any of these tests are eventually found to be clinically useful or, instead, prove disappointing like the dexamethasone suppression test, requires further research in the domain of biological psychiatry. A neuroimaging study is probably not warranted for the routine evaluation of geriatric depression but rather best reserved for those patients with neurological signs or symptoms.

Cognitive function should be assessed. A 6-item abbreviated version of the 20-item Mini-Mental State Examination has a sensitivity (88%) and specificity (89%) for dementia similar to the full 20-item measure.²⁸ The patient is asked to state the year, month, and day of the week, and to remember 3 objects (eg, "apple, table, penny") several minutes after the investigator names them. Three or more errors is considered a positive test. While bipolar disorder accounts for less than 5% of depression in primary care, it requires special treatment. Therefore, a single screening question is warranted, such as "Have you ever been prescribed lithium, or told you were manic-depressive or had bipolar disorder?" Screening for substance abuse (eg, the CAGE [C Have you ever felt the need to cut down on your drinking? A Have you ever felt annoyed by criticism of your drinking? G Have you ever felt guilty about your drinking? E Have you ever taken a drink (eye opener) first thing in the morning?] questions²⁹ for alcohol) is important since its presence requires more than just depression treatment but also primary or concurrent substance abuse therapy.

Assessing suicidal risk is mandatory in every patient suspected of being depressed, since it is unclear if any clinical factors (eg, severity of depression, social isolation, gender) are particularly predictive.^{30 - 31} Older adults account for 12% of the US population but 20% of the more than 30 000 suicide deaths in the United States annually.⁴ Recent studies of completed suicide have confirmed its close association with major depression, especially in elderly patients.³² The most striking increase in the suicide rate has been among those older than 80 years, with the highest risk group being elderly white men 85 years and older whose suicide rate is 6 times that of the general population.¹⁴ Asking a single screening question is usually adequate, such as "Have you had thoughts about dying or that you'd be better off dead?" A negative response typically puts the patient in a very low-risk category.³³ Those who respond affirmatively should be further questioned about an actual suicidal plan, previous attempts, or possibly access to firearms or stockpiled medications that may be lethal in overdose. Thoughts about death are common in depressed patients and by themselves do not mandate a mental health referral. However, suicidal ideation or actual plans are more serious and typically warrant expedited psychiatric consultation. Mr S never expressed suicidal thoughts and thus was an appropriate candidate for outpatient treatment by either his primary care physician or a consulting psychiatrist.

There is no single diagnostic test that can be routinely recommended from an evidence-based standpoint. Despite inconclusive evidence regarding the association between thyroid disease and depression, a TSH measurement should be obtained in patients with treatment-refractory depression, as hypothyroidism may contribute to this condition.²⁷ Patient sex may also influence the decision to obtain a TSH measurement since routine screening for subclinical hypothyroidism is recommended in women older than 50 years even in the absence of any symptoms.³⁴ I often will order a complete blood cell count and comprehensive chemistry profile if these have not been obtained for some time and make sure the patient has undergone recommended cancer screening. However, this is more to make sure I have not missed something and seldom changes either the diagnosis of a primary depression or depression-specific therapy.

Most patients with depression who present in the general medical setting initially volunteer physical rather than emotional symptoms.^{35 - 36} Rather than saying, "I'm depressed," they report fatigue, trouble sleeping, headaches, or other somatic complaints. The first step is often linking their symptoms to depression and persuading them that this is not a moral weakness or "all in their heads." Older patients may not be more likely than younger patients to perceive depression as stigmatizing, but those who do are more likely to discontinue treatment.³⁷ Providing them with a medical basis for depression—a neurotransmitter or "chemical" imbalance—can be useful. It is also helpful to emphasize that depression is a very common condition (1 out of 10 outpatients, and 2 to 3 times higher than this in patients with chronic medical disorders^{1 - 2} ) and that its symptoms are eminently treatable. Emphasize that recovery is the rule.

Describing treatment options and eliciting patient preferences is the next step after establishing the diagnosis. The 3 main treatment options include watchful waiting, antidepressant medication, and formal psychotherapy. Watchful waiting is one option for patients reluctant to begin depression-specific treatment and whose symptoms are of recent onset, nondisabling, and below the threshold for major depression.^{24 ,38} Simple office counseling provided by primary physicians—while not formal psychotherapy—might have some therapeutic benefit in mild cases of depression, and physicians can acquire the basic communication skills in as little as 2 to 8 hours of training.^{38 - 40} Patients should also be "activated," that is, instructed to have a daily schedule, plan pleasurable activities, and exercise.^{1 ,24 ,38}

Antidepressants have become safer and simpler to prescribe and most physicians can be comfortable with at least several classes of agents (Table 1). Well-established for the treatment of major depression, antidepressants also can be beneficial for older patients with dysthymia or minor depression persisting longer than 4 weeks.⁴¹ No class of antidepressants has proven more efficacious than another in patients of any age, including older adults.^{42 - 46} However, selective serotonin reuptake inhibitors (SSRIs) and other newer agents have greatly surpassed tricyclic antidepressants in usage because of greater safety in overdoses, simpler dosing and titration, and a different and sometimes more favorable adverse effect profile.⁴⁷ The use of tricyclics has particularly diminished in older patients for whom anticholinergic and cardiovascular adverse effects can be especially worrisome.⁴⁸ The SSRIs remain the most commonly prescribed class of antidepressant, and specific SSRIs are similar in both effectiveness and adverse effect profiles.⁴⁹ Other newer antidepressants include bupropion, venlafaxine, mirtazapine, and nefazodone.

When prescribing antidepressants, one should explain the time course of both potential adverse effects (which occur early but often diminish within 1-2 weeks) and expected benefits (developing gradually over 2-4 weeks). The common misconception that antidepressants are habit-forming should be corrected. Finally, compliance should be addressed directly to preempt premature discontinuation. As many as one third of primary care patients stop taking newly prescribed antidepressants within 4 to 6 weeks, and less than half continue their medication for 6 months or longer.^{1 ,50} This proportion may be even higher in older adults.^{51 - 52} Several educational messages provided at the time of the initial prescription have been shown to decrease discontinuation rates, including: (1) take the medication daily, even if feeling better; (2) antidepressants must be taken for 2 to 4 weeks for a noticeable effect; and (3) do not stop taking the antidepressant without checking with the physician.⁵³

As detection of depression has improved, monitoring outcomes and adjusting treatment has been identified as the "next frontier" in quality improvement.⁵⁴ Compliance with the Health Plan Employer Data and Information Set (HEDIS) requires 3 visits within the first 12 weeks of initiating treatment. Telephone contacts by the physician, nurse, or trained office staff may be reasonably substituted for actual clinic visits in a number of patients.⁵⁵ One common follow-up schedule is a visit or call at 1 to 2 weeks to assess adverse effects and compliance, at 4 to 6 weeks to assess response, and at 8 to 12 weeks to assess remission. Sequential administration of the Patient Health Questionnaire depression module (PHQ-9) is one means for monitoring the number and severity of depressive symptoms.⁵⁶ This self-administered questionnaire grades the severity of the 9 DSM-IV depressive symptoms and has been validated in 6000 outpatients. Numerous other self-administered depression measures are also available.²⁵

Once remission has been achieved, antidepressants should be continued for a minimum of 4 to 9 months since this is a high-risk period for relapse.^{14 ,54} Indeed, Mr S had initially responded to a low dose of venlafaxine, but the stresses of moving to a new home led to worsening of his depression. The dose was appropriately increased and Mr S again improved.

Patients with 3 or more episodes of major depression or 2 severe episodes should be considered for maintenance (ie, lifetime) treatment because of the high risk of future recurrences. Dysthymia would be another indication for chronic antidepressant therapy. Mr S has apparently been in remission for more than a year and does not report prior episodes of major depression. If he wishes, his antidepressant could be discontinued. Titrating off rather than suddenly stopping an antidepressant is advised to prevent a discontinuation syndrome.⁵⁷ Now that Mr S and his family know the clinical features of depression, recurrence of his symptoms for a period exceeding 2 to 4 weeks should prompt reinitiation of treatment.

Numerous studies have shown that systems changes are often needed to improve outcomes of depressed patients in primary care.^{1 ,4 ,58 - 59} Physician education and depression screening may not be sufficient because of the time required to adequately treat depression as well as the competing demands of primary care.^{60 - 62} Support from a nurse or other office staff or collaboration with a psychiatrist may be helpful in patient education and activation as well as monitoring of therapeutic response. The multicenter IMPACT trial is currently comparing case management vs usual care in 1750 patients with late-life depression.⁶³

While many patients with depression can be treated by their primary care physician, there are a number of indications for either initial or subsequent referral to a psychiatrist as outlined in Article . There are also several types of partnership, such as collaborative care⁶⁴ (wherein depression-related visits with the primary care physician are augmented by 1 or several psychiatric consultation visits) and stepped care (wherein patients who fail to remit after 8 weeks of treatment by the primary care physician are provided additional visits with a psychiatrist).⁶⁵ Some patients must be persuaded that seeing a psychiatrist for depression is no different than seeing another type of medical specialist when needed, such as a cardiologist for heart disease. A second barrier can be limitations in access or reimbursement for mental health care. Communication between primary physicians and mental health professionals is variable⁶⁶ and can be a third barrier because of confidentiality concerns, separate record systems, and traditional practices.

Suicidal thoughts or, in particular, plans to commit suicide
Substance abuse (alcohol or illicit drugs)
Bipolar disorder
Psychosis (hallucinations or delusions)
Psychotherapy needed as primary or adjunct treatment
Drug-refractory (more than 2 or 3 failed antidepressant trials)
Complexity due to medical or psychiatric comorbidity

Mr S had a health plan with ready access to mental health care. Because of Mr S's complicated cardiac history and complex medication regimen, his primary physician elected an immediate psychiatric referral rather than prescribing antidepressants himself. Care provided by the psychiatrist was perceived as beneficial by both Mr S and his wife, reflecting the pervasive effects that depression can have on the family as well as the patient.

Three evidence-based types of time-limited psychotherapy are used to treat depression: cognitive behavioral therapy (CBT), interpersonal therapy (IPT), and problem-solving therapy (PST).^{44 - 45 ,54 ,67} For mild to moderate major depression, CBT and IPT (both 8-20 visits) and PST (4-8 visits) have been shown to be as efficacious as antidepressant medication, although improvement is initially slower than with medication and the duration of effect has not been clearly established.⁵⁴ Any of these time-limited psychotherapies should focus on current problems and aim at symptom reduction rather than personality reconstruction.⁵⁴ The cognitive part of CBT concentrates on identifying negative thought patterns, challenging those patterns, and replacing them with positive thought patterns. The behavioral part of CBT encourages increasing the quantity of rewarding activities. Problem-solving therapy is a briefer variant that concentrates on a repeated cycle of identifying small problems, generating multiple solutions, evaluating them, testing out the best solution, and reviewing the results. Interpersonal therapy focuses on personal stresses and relationships that often precipitate depression.

Psychotherapy may be used in patients who prefer not to take antidepressants who have complex psychosocial problems, or as additive treatment in those who fail to achieve remission despite an adequate trial of 1 or more antidepressants. Many argue that for severe depression, the evidence favors an antidepressant as part of the initial treatment, either alone or in combination with psychotherapy.^{68 - 69} However, some evidence suggests that psychotherapy (particularly CBT) may be just as effective as antidepressant therapy regardless of depression severity.^{70 - 71} Combined therapy may be more effective than either treatment alone and should be considered, especially in patients responding poorly to monotherapy.

Major depression with melancholic or psychotic features is unlikely to respond to psychosocial treatments alone and typically requires somatic therapies—medications or electroconvulsive therapy. Indeed, electroconvulsive therapy is a safe and highly effective treatment for those with severe or otherwise treatment-refractory depression.¹³

Mr S's family initially recognized his depression and encouraged him to seek care. In addition, his wife accompanied him on at least some of his visits to the psychiatrist and seemed to find them beneficial. Family members may observe symptoms or behavior in their depressed relative, which can be important to share, not only for establishing the diagnosis, but also for monitoring treatment response. At the same time, patients may benefit from one-on-one visits with their therapist, particularly if they need to discuss confidential matters or issues in family relationships. Thus, one may need to negotiate with the patient when to have joint vs individual visits. The family should also be involved when the patient has features of severe depression, such as suicidal ideation, psychotic features, or profound vegetative signs or impairment. An alliance with the family may also be helpful when there is noncompliance with therapy, including patients with comorbid medical illnesses and polypharmacy. Activation is a valuable adjunct to treatment, and the family may assist in this as well.

Mr S wonders whether he can discontinue taking his antidepressant medication. Since this is his first episode of major depression, discontinuing medication after 4 to 9 months of remission is an acceptable option. While some studies suggest that depression occurring in late life is more likely to be chronic,^{14 ,72 - 73} the evidence is inconclusive.¹³ Also, cardiovascular disease is associated with a higher risk of depression, and depression in turn is a risk factor for increased cardiovascular mortality.⁷⁴ However, it is not yet established that patients whose depression stays in remission remain at increased risk, or that treatment of depression lowers cardiovascular mortality.⁷⁴ Thus, a trial period without antidepressants is reasonable as long as Mr S and his family notify their physician if symptoms recur. Because of his illness, Mr S and his wife have been reluctant to travel. However, staying active and pursuing pleasurable activities is beneficial for depression^{24 ,38} and, therefore, travel can be encouraged.

A PHYSICIAN: Is there any evidence that the combination of psychotherapy and antidepressants is better than either alone?

DR KROENKE: For mild to moderate depression, either psychological treatment or medication is probably equally effective. There is evidence that the combination may be better, particularly in patients with more severe, chronic, or recurrent depression.^{71 ,75 - 76} The question is do you use them both at the beginning, or do you start with one or the other? Previous studies have shown that medication or psychotherapy as single treatments can bring about improvement in 50% to 70% of people with depression.^{4 ,13} In my practice, I use the combination if patients do not respond to medication. Typically, I offer medication first, because as an internist I can prescribe medication but do not have the time or skills to do psychotherapy. Incorporating patient preferences is important because some patients do not want to take medication; in fact, as many as one third of people who start taking antidepressants stop within the first month.^{49 - 50} Thus, the relative roles of medication and psychological treatment in a particular individual depend on patient preferences, clinical response, chronicity or complexity of depression, and factors such as access and reimbursement.

A PHYSICIAN: Could you comment further on the possible organic component of the depressive syndrome?

DR KROENKE: As I mentioned, secondary depression due to hormonal disturbances (eg, glucocorticoid excess, hypothyroidism) or medications is uncommon. Neurological disorders such as stroke, dementia, and Parkinson disease are an important cause of depression in the elderly; while some organic component may be involved, it has been difficult to disentangle.^{6 ,77} The current approach is still to consider the neurological disorder and depression as comorbid conditions. In other words, physicians should treat the coexisting depression as they would in other depressed patients, with antidepressants and/or psychotherapy.

A PHYSICIAN: In how many patients is excessive sleep, rather than too little sleep during the night, a symptom of depression?

DR KROENKE: Mr S did sleep excessively. We often think of trouble sleeping and loss of appetite as symptoms of depression. Some people actually sleep more or have increased appetite and weight gain. These features have sometimes been called "atypical depression" and are less common. However, in a substantial minority of patients, increased sleep or daytime napping is a symptom of depression.

A PHYSICIAN: Some of the newer medications are specifically advertised as helping with sleep. Do you think that certain antidepressants improve sleep state more than others?

DR KROENKE: The ARTIST [A Randomized Trial Investigating SSRI Treatment] study we just completed comparing 3 SSRIs did not find any differences among them.⁴⁹ As far as the newer classes of antidepressants, in terms of sleep, research would have to separate what has been shown in the laboratory with what happens clinically. It is possible that some of the new antidepressants are more effective, but the problem is they have not been compared head-to-head with other antidepressants.

DR BURNS: Mr and Mrs S, do you have any questions or comments?

MRS S: I would just like to emphasize the integration by the psychotherapist of the wife and the family in the treatment—that for us has been critical. The medication is important for him, but for me the involvement is the key.

MR S: Family cooperation and help is incredibly important—I do not know where I would be without it.