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CHAPTER 28 DEPRESSION

CHAPTER 28 DEPRESSION
Practice of Geriatrics
CHAPTER 28 DEPRESSION
Donald P. Hay, M.D., Kari L. Franson, Pharm.D., Linda Hay, Ph.D. and George T. Grossberg, M.D.
Epidemiology
Diagnosis
Pharmacotherapy of Geriatric Depression
Nonpharmacologic Treatment
Compliance
Electroconvulsive Therapy
EPIDEMIOLOGY
At any time in life, depression is a devastating illness. It has been found to be more disabling than the other more commonly recognized physical illnesses of diabetes, hypertension, and arthritis. The estimated prevalence of depressive disorders in the elderly varies widely. Clinicians often attribute this variability to the difficulty of recognizing depression in the geriatric population. Because of this, in a recent article it was stated that “at least 15% to 20% of community elders have a type and degree of depression warranting clinical and public health attention.”1 According to the criteria listed in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, approximately 5 million of 31 million Americans aged 65 or older suffer from depression. It is reported that 1 million of these suffer from major depressive disorder and that minor depression, dementia syndrome of depression, and depression secondary to a medical illness have higher prevalence rates in the elderly than in the adult population as a whole.
The prevalence of depression also varies according to the setting in which the geriatric patient is seen. It is estimated by a Department of Health and Human Services Consensus Panel that 15% to 20% of nursing home patients have symptoms of depression, whereas only 5% of elderly patients seen in primary care clinics report depression. This figure drops even further in healthy, community-dwelling elders, of whom only 3% report depressive symptomatology.2 However, the highest rate of depression occurs in the elderly, medically ill, inpatient population, in which rates as high as 40% have been found.3
Without regard to actual prevalence, late-life depressive disorders are associated with increased morbidity and mortality and take a significant toll on the individual and society. Unfortunately, for every individual who seeks medical attention for depression, a significant number remain unidentified, undiagnosed, or untreated.
DIAGNOSIS
In considering mood disorders in older adults, the clinician must be aware of major depression, which is the most debilitating and most closely associated with suicide risk, chronic low-grade depression or dysthymia, and mood disorders secondary to an underlying medical condition or a prescribed or over-the-counter (OTC) medication.
Major Depression
According to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-IV), the diagnosis of major depression requires the presence of five vegetative signs and symptoms, one of which must be either lowered mood or loss of interest and pleasure present on a continuous basis for at least 2 weeks. Table 28-1 lists the DSM-IV criteria for major depression. Cutting back on activities may be an early warning sign of depression in the elderly. Almost always, appetite is adversely affected resulting in concomitant weight loss; weight gain may occur, albeit rarely, especially in younger persons. Sleep is commonly affected, and the most severe depressions are accompanied by terminal insomnia or early-morning awakening. Lack of energy or easy fatigability is often a presenting feature in the elderly, perhaps accompanied by spending too much time in bed. If one encounters feelings of worthlessness or excessive or inappropriate guilt or remorse, caution is advised because these individuals may be moving into a major depression with psychotic features (accompanied by delusions or hallucinations). The latter have a close association with suicide.

TABLE 28-1 DIAGNOSIS OF MAJOR DEPRESSION

When problems with concentration and thinking are prominent, the dementia syndrome of depression is diagnosed; this is often mistaken for conditions such as Alzheimer’s disease. However, if the cognitive changes are due solely to depression, they should resolve once the depression is ameliorated. It is also important to pay attention to recurrent thoughts of death and to inquire about thoughts or plans for suicide. Obviously, anyone who is deemed an active suicide risk requires prompt intervention and close observation.
Dysthymia
Subsyndromal depression and dysthymia are terms used to describe a less acute occurrence of depression. This condition is present when fewer than five of the nine symptoms required for the diagnosis of major depressive disorder have been present for at least 2 years. Dysthymia is similarly treatable with psychopharmacologic and psychotherapeutic measures. Decisions about when and how to treat dysthymia include consideration of the functional level and degree of impairment of the patient. Antidepressants are relatively benign and in many cases prove helpful.
All psychiatric illnesses, including depression and dysthymia, are affected by and in turn affect medical co-morbidities. The geriatric population experiences more medical illnesses of a more chronic nature than younger populations. The symptoms of medical illnesses and the medications used to treat them can contribute to the initiation or worsening of depression. Depression in turn, especially that of a more chronic nature, can exacerbate medical illnesses by many pathways, including decreased physical activity, interference with sleep patterns, and lack of appetite, which sometimes leads to nutritional compromise. Consideration of the evaluation and treatment of subsyndromal depression requires attention to the current and past medical history as well as assessment of current medications. Table 28-2 lists some of the medical conditions and medications that may be associated with symptoms of depression in the elderly.

TABLE 28-2 PHARMACOLOGIC AND MEDICAL CAUSES OF DEPRESSION

The Depression Evaluation
Table 28-3 highlights the fundamental features of a thorough depression assessment. This assessment is done once before treatment is initiated to rule in or out any underlying medical disorders that may be contributing to the symptoms of depression. Obviously, the induction process starts with a thorough history obtained from the patient, family, and other available informants in an attempt to tease out the signs and symptoms of depression. It is well known that older adults rarely complain of or use the term depression. Many may present initially with vague, nonspecific somatic complaints. However, lurking in the background is often a clinically significant depression.

TABLE 28-3 THE DEPRESSION EVALUATION

A head-to-toe physical and neurologic examination is vital to identify underlying medical problems. A psychiatric evaluation together with the use of a screening tool such as the geriatric depression scale (GDS)4 will help to solidify the diagnosis (Table 28-4). A laboratory evaluation is important to detect metabolic, infectious, endocrine, hematologic, nutritional, and other abnormalities that may present with depressive symptoms or exacerbate depression in older adults. Of equal importance is a thorough review of any and all prescribed or over-the-counter medications the patient may have access to including alcohol, which may trigger symptoms of depression.

TABLE 28-4 GERIATRIC DEPRESSION SCALE

PHARMACOTHERAPY OF GERIATRIC DEPRESSION
Treating depression in the elderly population is difficult given the high variability in clinical presentation and treatment response. Seventy percent of patients with an acute major depressive episode respond to the first antidepressant used. This response rate increases to 80% to 85% with the trial of a second agent. However, the definitive response to antidepressants is marred by a high placebo response rate, reported to be as high as 40%, and a delay in response of 4 to 8 weeks. When depression is complicated by psychosis, the response rate to an antidepressant alone is less than a 50%. In clinical practice, however, the response rate in elderly patients is reported to be much lower because of subtherapeutic dosing and shorter duration of treatment. Because depression is recognized as a recurrent disease, with a relapse rate of over 50%, the current literature suggests that, following an acute depressive episode, therapy should be continued for 6 to 12 months.5 In elderly patients, who often have had two previous episodes of depression, maintenance antidepressant therapy is suggested for 4 to 5 years.6 A history of two previous episodes plus a family history of depression, or a history of three or more episodes brings a recommendation for lifetime maintenance therapy.
To be able to prescribe an antidepressant properly for an elderly patient, the clinician must have knowledge of (1) the specific features of the diagnosis; (2) concomitant diseases that may either contribute to the depression or complicate the treatment; (3) concomitant medications that may either contribute to the depression or complicate the treatment; (4) previous antidepressant response; (5) the family history of response to antidepressant therapy. Choice of the appropriate antidepressant also requires knowledge of the various theoretical mechanisms of action and profiles of adverse effects. The drugs used to manage depression have high interpatient variability. Clinicians should use extra caution: The toxicities seen in the elderly are not dose dependent; rather, they are concentration dependent. This distinction is critical because the elderly normally require only one third to one half the dosage used for a young adult to acquire a therapeutic effect. This reduced dosage requirement results primarily from alterations in volume of distribution and liver metabolism in the elderly. Clinicians should be aware that, owing to these changes, drug accumulation may occur, and drugs with long half-lives are particularly problematic.
Tricyclic Antidepressants
Tricyclic antidepressants (TCAs) remain the gold standard for therapy. Of these, however, only the secondary amines nortriptyline and desipramine are regularly used in the elderly. This restricted use is due to the relatively nonspecific mechanism of action possessed by the tertiary amines amitriptyline, imipramine, trimipramine, and doxepin (Table 28-5). These agents’ polypharmaceutical actions include inhibition of presynaptic serotonin and norepinephrine reuptake and prohibitively high anticholinergic effects, inhibition of alpha-1-adrenergic action (orthostatic hypotension), inhibition of histamine-1 receptor action (sedation), and prolongation of cardiac repolarization (leading to lengthening of the QT interval).7 Because of these effects, tricyclic agents are contraindicated in many elderly patients who have cardiac conduction defects.

TABLE 28-5 TRICYCLIC ANTIDEPRESSANT THERAPY

Caution is required in the geriatric patient with cardiovascular disease, narrow-angle glaucoma, benign prostatic hypertrophy, urinary retention, or a history of seizures. Additionally, clinicians should be aware of the relative supersensitivity of the elderly to anticholinergic effects, which can cause profound confusion. These agents should be given at bedtime to avoid the consequences of the previously noted adverse effects. Caution is also required in patients with suicidal ideation because lethal doses can be achieved with as little as a 2-week supply of tricyclics. Many clinicians report that the availability of therapeutic serum drug concentrations of nortriptyline and desipramine favors their use in the elderly. However, in a review of therapeutic serum drug concentration usage, it was reported that toxicity was seen at the same rate in groups that had therapeutic drug monitoring and those that did not. Based on this report, therapeutic drug monitoring may be appropriate in patients with toxic reactions, nonresponders without adverse effects, and the elderly. Even within the therapeutic range, geriatric patients should be monitored for signs and symptoms of overdose, whether mild (confusion and urinary retention) or severe (arrhythmias, hyperpyrexia, and respiratory depression). The general rule when initiating antidepressant therapy (with tricyclic agents or otherwise) in the elderly is to “start low and go slow” and titrate doses to effect.
Selective Serotonin Reuptake Inhibitors
The selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, sertraline, paroxetine, and fluvoxamine (Table 28-6). These agents are relatively specific for inhibiting the reuptake of serotonin and subsequently increasing serotonin neurotransmission. Because of this selectivity, the SSRIs lack the myriad adverse effects seen with the tricyclic antidepressants. It is for this reason that both psychiatrists and general practitioners are using SSRIs as first-line therapy for the treatment of depression. The SSRIs are structurally unrelated, well absorbed, highly protein bound, and extensively metabolized, yet they have various routes of metabolism.8 The 7- to 9-day half-life of the norfluoxetine metabolite may lead to significant accumulation of this metabolite in the elderly (see Table 28-6). Compared to tricyclic antidepressants, SSRIs reportedly cause more gastrointestinal side effects including nausea, vomiting, and stomach upset. These adverse effects are believed to be self-limiting and thus may last only 1 to 3 weeks; such adverse effects may also indicate a too-rapid titration of dose that may be alleviated by lowering the dose. Another helpful approach is to recommend eating some food 20 to 30 minutes before the patient takes the medication. The neurologic side effects of SSRIs can be more persistent. Fluoxetine, for example, can cause significant anxiety and insomnia, an occurrence that necessitates a change to a less stimulating therapy. When initiating therapy with SSRIs it is best to start with a morning dose of the drug because of the stimulating effects, but these agents can be given at bedtime if the patient reports sedation.

TABLE 28-6 ANTIDEPRESSANT THERAPY WITH SELECTIVE SEROTONIN REUPTAKE INHIBITORS

Atypical Antidepressants
Other options for the treatment of depressed geriatric patients include atypical antidepressants (sometimes termed second-generation or newer antidepressants) (Table 28-7). These agents’ proposed mechanisms of action do not fit into the categories listed earlier. Maprotiline is a rarely used tetracyclic antidepressant with a long half-life that is believed to inhibit presynaptic norepinephrine reuptake. Although seizures are reported to occur three times more frequently than with tricylics, maprotiline is associated with fewer cardiac arrhythmias. Amoxapine inhibits presynaptic reuptake of norepinephrine and serotonin, and its metabolite 8-hydroxyamoxapine blocks dopamine activity. Because of this inhibition, the geriatric patient may be at increased risk of developing parkinsonism, akathisia, or possibly tardive dyskinesia. The proposed use of this agent for psychotic depression is not warranted because when psychotic symptoms resolve, the antipsychotic should be discontinued to decrease the neurologic effects. With overdosage, amoxapine causes fewer cardiac effects but carries a risk of seizures, irreversible neurologic damage, and renal failure.

TABLE 28-7 ATYPICAL ANTIDEPRESSANT THERAPY

Bupropion is a popular antidepressant in elderly patients who are unable to tolerate other antidepressants because it has minimal sedative, anticholinergic, and cardiovascular properties. The mechanism of action of bupropion was believed to result from inhibition of dopamine reuptake; however, this inhibition has been found to be weak and may affect the norepinephrine and serotonin systems only slightly. Because of the increased threat of seizures with single doses of more than 150 mg, it is recommended that bupropion be given in divided doses despite a half-life that has been reported to be as long as 15 hours. Doses should be initiated at 75 mg twice daily and increased as tolerated. Because insomnia is common, a bedtime dose should be avoided.
Trazodone and nefazodone, which are classified as serotonergic drugs but not SSRIs, are believed to both inhibit serotonin reuptake and antagonize the serotonin-2 postsynaptic receptor. The postsynaptic receptor inhibition is thought to be responsible for the effectiveness of these agents in the anxious patient. Trazodone inhibits alpha-1-adrenergic receptors, giving rise to clinically significant orthostatic hypotension that peaks 1 to 2 hours after the dose and limits the clinical usefulness of this weak antidepressant in the elderly. The alpha-2-adrenergic effects of trazodone can rarely produce priapism. Both agents produce sedation with next to no anticholinergic effects, cardiac conduction abnormalities, or seizures, and both have been found safer than tricyclic antidepressants in overdose.7 Nefazodone has a 2- to 4-hour half-life and is metabolized into three active metabolites that have half-lives of less than 24 hours; thus it requires twice daily dosing. Because of the possibility of sedation and dizziness, doses should be started at or below 50 mg twice daily.
Venlafaxine selectively inhibits the reuptake of both serotonin and norepinephrine from the synaptic cleft. Interestingly, venlafaxine has been found useful in patients in whom previous treatment has failed. Thus, many clinicians are using this agent as a safer second-line therapy in elderly patients who have failed to respond to an SSRI. In contrast to most psychoactive agents, venlafaxine is metabolized to an active metabolite that is excreted through the kidneys, thus requiring dosage adjustments in elderly patients with renal impairment. Side effects include nausea, somnolence, insomnia, and confusion. Venlafaxine is less arrhythmogenic than tricyclics but can cause small increases in blood pressure.
Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors (MAOIs) are believed to exert their therapeutic effect by blocking the synaptic destruction of biogenic amines. Phenelzine and tranylcypromine block the enzyme irreversibly; however, a newer reversible MAOI (meclobemide) is being used outside the United States. The MAOIs have not been well studied in the elderly because of their limiting adverse effects and drug interactions. For this reason, these drugs are often reserved for patients who have not responded to tricyclics or SSRIs. Yet there exists a body of literature indicating that the MAOIs may be effective for “atypical depression.” The possibility of hyperpyrexia or a serotonin syndrome precludes combination therapy with other antidepressants. Other drug-drug or drug-food interactions can occur with over-the-counter cold products (which contain sympathetic amines), and foods containing high levels of tyramine such as aged cheeses, cured meats, and beer. These interactions result in a hypertensive crisis, and the clinician should be aware of the early warning signs such as stiff neck, occipital headache, nausea, vomiting, sweating, flushing, and palpitations. The MAOIs have significant adverse effects as well. Orthostasis is common and is best prevented by increasing the dosage gradually. Weight gain, sexual dysfunction, and edema may also occur. Overdosage results in palpitations, agitation, frequent headaches, hypertension, or severe orthostasis.
Stimulants
Sympathomimetic agents such as methylphenidate and dextroamphetamine stimulate presynaptic catecholamine release and inhibit reuptake. These agents have been shown to provide quick relief of depressive symptoms in small studies of medically ill, elderly patients. Unfortunately, the long-term efficacy or adverse effects of the stimulants are unknown in this population.
NONPHARMACOLOGIC TREATMENT
The nonpharmacologic treatment of depression in the elderly includes a variety of strategies, each reflecting the unique challenges of treating this population. In addition to the difficulty of distinguishing between depression and dementia, a juxtaposition of the two may occur, complicating treatment. Also, it is important to include the entire treatment team as well as the entire support system in the assessment and treatment process. The treatment team frequently consists of the primary physician, consulting psychiatrist, occupational therapist, social workers, and nurses. Proper assessment, education of the patient, day hospital care, social support services, and individual, group, and milieu psychotherapy should be considered to address the wide range of problems that may face the older individual working through issues of chronic illness or a major depressive disorder.
The choice of treatment for the elderly, as with younger populations, depends on the severity of the symptoms. Intensive psychosocial support is recommended in addition to hospitalization, medication treatment, or electroconvulsive therapy for elderly patients with more severe depressive episodes. For patients who have had a severe acute episode and for those who are more moderately depressed or who have dysthymia, long-term outpatient treatment that includes medication and psychotherapeutic strategies may be necessary.9
Assessment and education are important from the standpoint of compliance. Cohort issues arise even before the primary physician or geriatric psychiatrist begin to consider the possibility of a diagnosis of a major depressive disorder. The NIMH Consensus Development Conference of 1991 found, among other treatment issues, that depression in later life occurs in the context of numerous social and physical problems, and attentive and focused clinical assessment is essential.2 Many elderly individuals do not report depressive symptoms to health care providers because they believe these are to be expected. Depression is also often attributed to organic illness.10 All health care professionals working with the elderly should be well trained and knowledgeable about the symptoms of depression, and they should also know when to try to elicit the less obvious information from patients. Sources of information that may be vital in the assessment of the elderly include the patient’s spouse, siblings, and offspring. Family members may have observed details that may be critical for the clinician.
Education is an essential part of the diagnostic and treatment process. This process includes not only the patient and his or her family but also the primary care physician. Many elderly individuals as well as the general population are not aware of the biologic phenomenon of major depressive disorder. In presenting treatment options, an explanation of the rationale for medication treatment must be made to the patient and the family to ensure compliance. Much has been written about the need to coordinate all treatment of the elderly, including medication strategies and psychotherapy with family members.
There are many reports in the literature about the effects of psychotherapy and pharmacotherapy for elderly patients who have depression in the maintenance treatment phase.9 Most reports indicate that a combination of medications and psychotherapy is more effective than either psychotherapy or medication alone.
Cognitive behavioral techniques have been found to be effective in providing patients with skills such as enhancing coping abilities, promoting health, and improving quality of life. Education about the effects of negative thoughts on mood and training to identify these themes are very helpful. Behavioral techniques include training in ways to increase experience with pleasant events and decrease the occurrence of unpleasant events.
Group therapy provides an orientation to others as well as the use of individual psychotherapy techniques. Life review therapy is helpful in a group and allows individuals to focus on their life memories in a positive environment.
COMPLIANCE
The effectiveness of any type of treatment for depression in the geriatric patient depends on the compliance of the patient with the treatment recommendations. The diagnosis and treatment of depression in the elderly can best be divided into three components: (1) identification of depression symptoms as such and subsequent diagnosis, (2) treatment, and (3) maintenance therapy. All three are critical, and failure in any one may result in continued suffering that could otherwise be treated easily, allowing the affected individual to lead a normal and healthy life. Because of the increase in longevity, diagnosis and effective treatment of an 80-year-old may normalize the quality of life for this individual for many years!
Compliance in the outpatient arena first requires a recognition and understanding by the patient of both the diagnosis and the treatment recommendations. The stigma of mental illness and a general unawareness of depression as a physical illness as well as multiple medical comorbidities, difficulty with transportation, and a fixed income may all lead to noncompliance. For these reasons, there is a special need at the first meeting with the patient and the family to develop a good “treatment alliance” to facilitate further diagnosis and effective treatment.11
Understanding the need for medication and the requirements for safe psychopharmacotherapy is similarly critical for successful treatment of the index episode and continued prophylaxis from recurrence in this frequently relapsing chronic illness. Elderly outpatients may not pay adequate attention to medication directions or may continue to take the drugs according to their own prior preference despite current recommendations.
Compliance in this population may be affected by many factors including forgetfulness, poor vision, and self-neglect secondary to an underlying and untreated depression, psychosis, or dementia. Other factors that may contribute to patient noncompliance include medication side effects, perception of lack of efficacy, and the feeling that improvement has been accomplished and taking the medication is no longer necessary.12
Side effects are the number one reason why geriatric patients discontinue medications, and it is therefore critical for the physician to choose the appropriate medication at the correct dose. Starting low and increasing the dosage gradually are the recommended methods for treating this population.
Occasionally the physician may encounter a patient who refuses to abandon older medications and older dosing strategies. In such situations it is always helpful to have the family present with the patient to help with a discussion of diagnosis and treatment recommendations.
ELECTROCONVULSIVE THERAPY
Electroconvulsive therapy (ECT) continues to be the single most effective treatment for major depressive disorder with or without psychotic features and for bipolar disorder, and it may be helpful for treating affective and psychotic disorders in elderly patients with movement disorders such as Parkinson’s disease and tardive dyskinesia.11,13,14 It is the treatment of choice for patients with psychotic delusional depression because it is usually not possible to treat these patients rapidly, safely, and adequately without incurring significant and dangerous medication side effects.
ECT is effective, works rapidly, and is extremely safe in this population. Unilateral placement of electrodes at adequate stimulation levels along with the use of pulsed square-wave stimulating equipment has been proved safe and effective without worsening of cognitive status.
Issues of compliance for this treatment are critical. Compliance is affected by fear and apprehension engendered by the myths and misrepresentation of this method as well as the difficulty of requiring continuation or maintenance therapy. Given the high incidence of medical comorbidities, which make the logistics for follow-up treatments more difficult, compliance may be further jeopardized. This situation therefore requires extensive effort by the physician to form an effective treatment alliance so that not only the initial treatment but also the continuation and maintenance therapy can be given as required. In this way the elderly patient can be maintained symptom free, and the frequent recurrences of this often recurrent and chronic physical illness can be prevented.
CHAPTER REFERENCES

1.
Gurland BJ, Cross PS, Katz S: Epidemiological perspectives on opportunities for treatment of depression. Am J Geriat Psychiatry 1996;4(4):S7–S13.

2.
U.S. Department of Health and Human Services: Consensus Statement: National Institute of Mental Health Consensus Development Conference: The diagnosis and treatments of depression in late life. Bethesda, MD, U.S. Department of Health and Human Services, 1991, pp. 1–6.

3.
Koenig HG, Blazer DG: Minor depression in late life. Am J Geriatr Psychiatry 1996;4(4):S14–S21.

4.
Yesavage JA, Brink TL: Development and validation of a geriatric depression screening scale: A preliminary report. J Psychiatr Res 1983;17(1):37–49.

5.
American Psychiatric Association: Practice Guideline for Major Depressive Disorder in Adults. Am J Psychiatry 1993;150(4)Suppl:1.

6.
Kupfer DJ, Frank E, Perel JM, Cornes C, et al. Five-year outcome for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1992;49:769–773.

7.
Preskorn SH: Recent pharmacologic advances in antidepressant therapy for the elderly. Am J Med 1993;94(Suppl 5A):2S–12S.

8.
DeVane CL: Pharmacokinetics of the newer antidepressants: Clinical relevance. Am J Med 1994;97(Suppl 6A):13S–23S.

9.
Schneider LS, Olin JT: Acute therapy for geriatric depression. Int Psychogeriatrics 1995;7:7–25.

10.
Martin LM, Fleming KC, Evans JM: Recognition and management of anxiety and depression in elderly patients. Mayo Clin Proc 1995;70(10):999–1006.

11.
Hay DP, Hay L, Renner J, Franson K, Hassan R, Szwabo P: Compliance and the treatment alliance in the elderly patient with serious mental illness. In Blackwell B (ed): Treatment Compliance and the Therapeutic Alliance. Amsterdam, Netherlands: OPA Overseas Publishers Association, 1997, pp. 295–308.

12.
McMullen P, Ross AJ, Rees JA: Problems experienced with medicines by psychogeriatric patients in the community. Pharm J 1991;247:182–184.

13.
American Psychiatric Association Task Force Report on Electroconvulsive Therapy: The Practice of ECT: Recommendations for Treatment, Training and Privileging. Washington, DC, American Psychiatric Press, 1990.

14.
Hay DP: Electroconvulsive therapy. In Kaplan HI, Saddock B (eds): Comprehensive Textbook of Psychiatry, 6th ed, Vol. 2. Baltimore, Williams & Wilkins, 1995.
ADDITIONAL READINGS
Depression Guideline Panel: Depression in Primary Care. Vol. 2: Treatment of Major Depression. Clinical Practice Guideline, No. 5. AHCPR Publication No. 93-0551. Rockville, MD, U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1993.
Hay DP, Hay L: Comprehensive Review of Geriatric Psychiatry, 2nd ed. Washington, DC, American Psychiatric Press, 1996.

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