Late-life depression appears to be a paradox in that while the prevalence of depressive symptoms increases with age, the number of individuals that are diagnosed with major depressive disorders declines with age. A possible cause of this may be that physicians tend to under diagnose depression in the elderly because they view it as "natural," or as a consequence of a serious medical illness.

Possible Causes

Some of the causes of late-life depression may be social or psychological. The elderly sustain many losses: their work with its meaningfulness, income and structured routine, their friends and loved ones, and their physical strength.

Other possible causes of depression in older adults may be medical illnesses that can appear as depression: hypothyroidism/hyperthyroidism, Cushing's disease, Parkinson's disease, cardiovascular and pulmonary disorders, vitamin B12 and folic acid deficiencies, carcinoma and stroke.

Coexistence with Chronic Illnesses

Late-life depression seems strongly correlated with the presence and severity of medical illnesses instead of a family history of depression. In general, the more severe the illness, the greater the odds that the individual will have a depressive disorder. Medical conditions associated with depression include endocrine disorders, arthritis, chronic pain states, cancer and post-myocardial infarction (MI) or heart attack and post-cardiac bypass surgery.

Research has shown that depression in people with myocardial infarction can be deadly. Depression in the immediate post-MI period is associated with a death rate three to five times higher than that seen after MI without depression. It can have major consequences for patients and families.

Depression can also lead to disability. One study of older women hospitalized for hip fracture noted that those who were depressed in the hospital after their surgery were less likely to be up and walking a year after the surgery than those who were not depressed. It can also amplify medical symptoms in older patients, especially pain, and may make drug side effects less tolerable.

Depression and Alzheimer's Disease

Several studies have suggested that depression may be associated with increased risk of Alzheimer's disease. But the precise relationship of depression to dementia remains unclear. Paula K. Ogrocki, Ph.D. of Duke University found that Alzheimer's disease patients who subsequently developed major or minor depression were more likely to have a first-degree relative with major depression. It is possible that the degeneration of Alzheimer's disease may uncover previously unmasked depression in patients. Depression can also exacerbate the memory loss of dementia. If clinicians are able to ask about a family history of depression when diagnosing dementia, they may be able to take a preventive attitude toward depression, and perhaps minimize memory loss.

Are patients suffering episodes of depression at risk for Alzheimer's disease later on? Julie Wetherell, a predoctoral student in the lab of Margaret Gatz, Ph.D. at the University of Southern California, studied depression in twins where one had Alzheimer's disease and the other one did not. In 50 pairs of twins taken from the Swedish twin registry, Wetherell found that individuals with a history of depression were four times more likely to develop Alzheimer's disease than their twins who had never been depressed. However, when the analysis was restricted to the 10 years before the onset of dementia, the likelihood of depression predating dementia was cut in half. Patients who develop a first episode of depression later in life should be treated and monitored closely for possible progression to Alzheimer's disease.

Different Symptoms

Depression in an older patient may manifest different symptoms than in a younger adult. The aging person often reports less change in mood and attitude and more of the body complaints such as constipation, headaches, and fatigue. Moreover, the older depressed patient may appear confused, have memory loss, and be agitated. These deficits in mental functioning are frequently ascribed too quickly to dementia. Because doctors expect to see dementia in this age group, there is a tendency to over diagnose it. In fact, approximately 12 percent of the elderly diagnosed as suffering from a dementia are thought actually to have a false dementia arising from untreated depression.

Suicide

Alarming Rate of Suicide in Elderly

While people over the age of 65 make up only 13% of the population, they account for 25% of all suicides.

• Each year more than 6,300 older adults take their own lives; approximately 17 a day.

• White males over the age of 80 have the highest suicide rate of all Americans.

• Over the age of 65, there is 1 suicide in every 4 attempts. In young people (15-24) there is one completion for every 100-200 attempts.

• In patients 75 years and older, 60 to 70% of suicides occur in people with diagnosable depression.

• 75% of older suicide victims have been seen by their primary care physician during the month preceding their death.

Source: American Association of Suicidology. Elderly Suicide Fact Sheet. 1996.

The increasing suicide rate in the elderly is a major clinical problem. According to Jane Pearson, Ph.D., chief of the clinical and developmental psychopathology program at the National Institute of Mental Health, the suicide rate for white males aged 80 or older has consistently been in the rate of 60 to 70 per 100,000 since 1985. That is six times the current overall national rate.

Although numerous strategies have been tested for finding and treating teenagers on the brink of suicide, the same is not true for the elderly. Almost all suicides by the elderly involve nonpsychotic, nonbipolar depression uncontaminated by substance abuse. This is the most treatable form of depression.

Brain Imaging

Patients with late-life depression have a high prevalence of brain structural and functional changes that distinguish them from young depressed patients. The brains of elderly depressed patients show several consistent structural alterations:

• Low frontal lobe volumes
• White-Matter and basal ganglia lesions
• Low caudate volumes
• Larger ventricular-brain ratios compared with age-matched controls.

One of the most common medical conditions associated with late-onset depression is the syndrome known as silent cerebral infarction (SCI) (i.e. destruction of brain cells) - also termed leukoencephalopathy. Magnetic resonance imaging studies of the depressed elderly show an unexpectedly high incidence of periventricular white-matter lesions in the frontal lobes and basal ganglia. While these lesions appear to be the result of "stroke," they do not result in motor or sensory symptoms - hence the term silent cerebral infarction. Studies have found that in comparison to age-matched early-onset depressives, late-onset cases show a much higher frequency of these white-matter lesions. The biggest risk factor for SCI seems to be carotid atherosclerosis (i.e. hardening of arteries), followed by a history of myocardial infarction.

Despite the high prevalence of brain structural changes in late-life depression, it is unclear whether these structural changes are a significant factor in the development or the course of the illness. Drs. Andrew F. Feuchter and Ian A. Cook (a NARSAD 1995 Young Investigator) of the University of California-Los Angeles are studying these structural changes using quantitative electroencephalographic (QEEG) coherence, a measure of the shared activity between different brain regions. They have found that the presence of periventricular hyperintensities (PVH), a type of white-matter disease found along the margins of the lateral ventricles, was associated with decreased coherence in the depressed patient.

Depression and Menopause

Depression may become evident for the first time during or after menopause, but it does not appear to have any unique features when it occurs during the menopausal years. A large survey, conducted by Myrna Weissman (1994 Selo Prize Co-Winner) at Columbia University, of symptoms in 422 women with major depression found no difference in symptoms (or treatment response) between those who were premenopausal and those who were postmenopausal. It appears that aging in and of itself is associated with an increased risk of depression. One-third of all depressions occur among persons age sixty or older, and it may be the aging process, rather than menopause, that contributes to the increased frequency of depressive symptoms among menopausal women. However, for women who have been suffering from menstrually related symptoms, menopause may be another period of vulnerability.

Special considerations in Treatment

Few placebo-controlled studies have been conducted using older depressed patients, therefore many of the existing treatments are based on data from a younger study population. Common misconceptions about old age and depression have contributed to the lack of clinical trials. These misconceptions include the idea that medications used to treat depression are dangerous to the older patient so it is safer to not treat or to undertreat depressive symptoms. Also, many Americans have a negative view of aging and falsely assume that depression is a natural part of aging.

Physicians treating late-life depression need to be aware of the effects of aging on treatment of depression. Changes in body functions associated with aging alter the body's response to medical treatment. As a person ages, he or she experiences a decrease in cardiac output, kidney and liver function. Chemicals in the body are metabolized by the liver and excreted by the kidneys. Because these organs are less proficient as people age, medications remain in an older person's body longer and have much stronger effects than in younger people. Lean muscle decreases and body fat increases as we age. Psychiatric drugs may be stored in these fatty deposits and released slowly by the body. Toxicity can occur due to this build up of medication.

Drug Interactions

Older people may be taking several medications for various health conditions and have an increased risk of drug-drug interactions when taking an antidepressant. Some of the medications used to treat physical ailments may cause depression.

Medications Sometimes Associated with Depression

Antihypertensives
clonidine (Catapres)
hydralazine (Apresoline Hydrochloride)
methyldopa (Aldomet)
propranolol (Inderal)
reserpine (Serpasil, Ser-Ap-Es, Sandril)

Antiparkinsonism Agents
levodopa (Dopar, Larodopa)
levodopa and carbidopa (Sinemet)
bromocriptine

Hormones
estrogen, progesterone, cortisone, prednisone

Physicians must therefore take an extensive list of all medications in use by the patient, including common over-the-counter remedies such as antacids, before prescribing an antidepressant.

Common practice in prescribing antidepressive medications to geriatric patients is to "start low and go slow", to avoid any complications with toxicity due to the physical makeup of the patient's body and other medications in use. It often takes longer for older individuals to fully respond to antidepressants than their younger counterparts, possibly as long as 12 weeks.

Orthostatic Hypotension

Of particular concern in older depressed patients, are potential cardiac side effects of antidepressant drugs. Orthostatic hypotension, a drop in blood pressure after rising too quickly, resulting in a dizzy or faint feeling, is associated with increased numbers of hip fractures and other injuries in the elderly. Patients with healthy hearts are rarely at risk for orthostatic hypotension but other factors often contribute to the risk for late-life patients. Muscle strength often decreases with age, increasing the chance of a fall. Previous heart failure contributes to a drop in blood pressure. Medications such as diuretics, nitrates, and vasodilating medications may also decrease blood pressure. Older patients taking tricyclics are particularly at risk for orthostatic hypotension. There is also an increased risk of heart attack and stroke.

Orthostatic hypotension is more common with use of the tricyclics, MAOIs, and trazodone. Antidepressants less likely to cause this condition include SSRIs, bupropion (Wellbutrin), nefazodone (Serzone), and venlafaxine (Effexor). The best option is to choose a medication less likely to cause a drop in blood pressure. Occasionally a doctor may feel it is best to keep a patient on a medication despite the presence of orthostatic hypotension, particularly if other treatment options have failed. A number of strategies may help the patient manage the condition, such as educating the patient about rising slowly and sitting back down if he or she feels dizzy, drinking fluids to avoid dehydration, and using support stockings to prevent pooling of blood in the veins. Other options include administering sodium chloride (salt) pills or using a low-dose stimulant to counteract the orthostatic hypotension. Many of the medications used to treat depression have some effect on blood pressure. For this reason, late-life depression patients should have their blood pressure monitored regularly.

Cognitive Impairment

Older people experiencing depression may exhibit signs of cognitive impairment leading to incorrect diagnoses of various dementing diseases, including Alzheimer's. Symptoms may include short term memory problems, word finding trouble, anomia (trouble associating the name of an object with the object itself), confusion, disorientation and delirium. Some antidepressant medications are also known to cause these symptoms in certain people. Cognitive impairment due to antidepressants occurs more often in mature patients than in their younger counterparts. Clinicians should rule out other conditions that cause similar symptoms, such as thyroid disease and dementia, as well as other medications that may have cognitive effects. If the antidepressant is suspected, the dosage can be lowered or the patient can switch medications.

Sexual Dysfunction

Sexual dysfunction due to antidepressant use can be distressing for any patient, and many patients are reluctant to discuss this problem. For older patients, other factors may contribute to sexual dysfunction. Around 80 percent of Americans 65 years and older have at least one chronic disease, such as cardiovascular disease or diabetes, that can impair sexual function. Medications used to treat high blood pressure, cardiac arrhythmias, ulcers, and irritable bowel syndrome may all cause sexual impairment. Antihistamines may also inhibit sexual function in women. Because physical changes due to aging can also decrease sexual desire and function, the clinician needs to assess sexual function before and during treatment with antidepressants and should address this possible side effect with the patient. Common sexual dysfunction associated with antidepressant use includes anorgasmia (having no orgasm), decreased libido, and delayed orgasm. These types of dysfunction are more often associated with the MAOIs, SSRIs, and tricyclics. Bupropion and nefazodone do not usually cause sexual impairment. Medications such as bethanechol (Urecholine), yohimbine (Yocon), or the antihistamine cyproheptadine (Periactin) may be prescribed to relieve delayed orgasm in patients taking antidepressants.

Trazodone (Desyrel) can cause priapism, a prolonged, often painful erection of the penis. Erections lasting more than an hour may cause permanent damage to the penis. Men using trazodone should be warned about this side effect and should contact their doctor immediately if they have a sustained erection for no reason.

MAOIs

Monoamine oxidase inhibitors (MAOIs) are known to be a safe and effective treatment in geriatric depression, although they are not widely prescribed for this population. Older patients respond well to MAOIs, including those who do not improve with tricyclics or some of the newer antidepressants. Studies have shown that demented patients have higher levels of monoamine oxidase in their bodies than age-matched controls, possibly making MAOIs especially effective in treating dementia related depression. As with other age groups, an SSRI should be tried first due to the drug and food restrictions necessary with use of MAOIs. Although late-life patients comply well with the diet restrictions, patients with cognitive defects should not be prescribed MAOIs unless dietary intake is carefully monitored.

The risk for orthostatic hypotension (drop in blood pressure) due to MAOI use is higher in older patients than other age groups. MAOIs can be sedating, a side effect that clinicians may want to avoid in some mature patients because it may impair regular daily activities. Foods that contain tyramine can interact with MAOIs, causing hypertensive crisis, a sudden increase in blood pressure. Toxic interactions can occur with MAOIs and SSRIs. When changing from fluoxetine (Prozac) to an MAOI, fluoxetine therapy should be discontinued for at least 5 weeks before starting an MAOI.

SSRIs

In the treatment of major depression, selective serotonin reuptake inhibitors (SSRI) are as effective as the tricyclics but SSRIs have some advantages. Side effects are fewer and less severe and they are safer in overdose. SSRIs have a low potential for causing seizures and very little effect on the cardiovascular system. Paroxetine (Paxil), the most selective of the SSRIs on the market in the United States, is not associated with weight gain, sedation, hypotension, or constipation. Side effects associated with SSRIs include nausea, vomiting, nervousness, insomnia, and sexual dysfunction. Some cognitive impairment may occur with higher doses of SSRIs.

The SSRIs are metabolized by the liver, therefore impaired liver function may slow the removal of these agents from the body. Clinicians should prescribe lower initial doses and increase levels of the medication more slowly than in younger patients. Fluoxetine has a longer half-life than the other SSRIs and may be biologically active in an elderly person for five or more weeks after discontinuing use. This may cause problems in older patients that must be removed from the medication due to other illnesses. Drugs that may have a toxic interaction with fluoxetine, such as monoamine oxidase inhibitors, should not be administered for at least 5 weeks after fluoxetine is stopped. Other medications that SSRIs are known to affect include propranolol (Inderal), warfarin (Coumadin), diazepam (Valium), digoxin, theophylline, and the tricyclic antidepressants.

Tricyclics

Cognitive impairment is most common with use of the tricyclic antidepressants. TCAs are also associated with increased risk for orthostatic hypotension and cardiac problems. They can be lethal in overdose. Common side effects include dry mouth, constipation, urinary retention, memory loss, and delirium. Although any of the tricyclics can be used safely in older patients with careful dosing, most clinicians use nortriptyline (Pamelor) and desipramine (Norpramine) because of the lower risk of toxicity.

The tricyclics can be divided by their chemical structure into secondary and tertiary amines. Secondary amines include nortriptyline (Pamelor) and desipramine (Norpramine) are considered safer than the tertiary amines such as imipramine (Tofranil), amitriptyline (Elavil) and doxepin (Adapin, Sinequan) for use in older patients. One study found nortriptyline to produce more favorable results than the SSRI fluoxetine (Prozac) in treating older patients with cardiac disease. Medication blood levels should be monitored to prevent overdose or inadequate treatment.

Psychostimulants

Some evidence suggests that psychostimulants may be helpful for elderly depressed patients who also have physical illnesses. Methylphenidate (Ritalin), commonly used in treating Attention Deficit Disorder in children, is the preferred stimulant for use in the elderly due to its shorter half-life compared to the other stimulants. These medications work more rapidly than antidepressants and help to increase energy. Stimulants can be used alone or in combination with other antidepressants. Patients taking this medication may experience an increase in blood pressure, nausea, and heart palpitations. Careful physician supervision is critical when used in conjunction with an MAOI antidepressant because of the increased risk of hypertensive crisis.

Bupropion

Bupropion (Wellbutrin) is used for both major depression and bipolar disorder. It is relatively safe in terms of cardiac effects, even in patients with cardiac disease. Bupropion does not cause hypotension or tachycardia (rapid heart beat). It also does not cause significant sedation, cognitive impairment, or pose a significant risk of sexual dysfunction. One potentially dangerous side effect is the small risk of seizures in people taking this medication.

ECT

Electroconvulsive therapy (ECT) is highly successful for the treatment of major depressive disorder; there is approximately a 90% chance that ECT will improve symptoms of a patient with major depressive disorder. It does not, however, work on most cases of atypical depression or for anxiety disorders. For this reason it is very important that an accurate diagnosis is made prior to beginning electroconvulsive treatment. Patients treated with ECT feel significant benefits from the treatment generally within one week. For a suicidal patient who cannot wait 3 or more weeks for an antidepressant to take effect or for a patient who is not eating and is malnourished, ECT can prove to be a lifesaving treatment.

For people who cannot take antidepressants due to poor health, ECT is used as an alternative treatment method. There is a risk of a temporary change in blood pressure for a short period of time immediately following the procedure. Although the majority of these changes disappear without complication, patients with a history of high blood pressure or other cardiovascular problems should have a cardiovascular consultation prior to starting this therapy. Overall, ECT has fewer adverse cardiac effects than antidepressant medications, making it a potential treatment for depressed patients with cardiovascular problems.

Psychotherapy

Used alone or in conjunction with medication, psychotherapy can play an important role in the treatment of late-life depression. Major changes associated with aging, such as the loss of loved ones, financial changes, and health concerns, may increase vulnerability to depression. If these factors are not addressed, they may complicate treatment and delay response to antidepressants. Psychosocial treatments such as cognitive/behavioral therapy, interpersonal therapy, and problem solving are effective in treating geriatric patients, especially in mild to moderate depression. Studies have shown that patients receiving psychotherapy in addition to medication are more likely to continue taking their medication than those who do not receive psychotherapy.

References

Considering Depression Across the Ages. Psychiatric Times. Supplement April 1996.

Baron-Faust, Rita. "Mental Wellness for Women." William Morrow and Company, Inc. New York. 1997

"Late Life Depression: Recent Advances in Assessment and Treatment" from Institute on Psychiatric Services Symposium held Oct. 8, 1995 in Boston, MA.

Lauerman, John. "Depressed Elderly Remain Undertreated Despite Antidepressant >Golden Age.' Psychiatric Times. February 1997.

Papolos, Demitri and Janice. Overcoming Depression. HarperCollins Publishers, San Francisco, 1997.

Rathe Pray, Diana, editor. "Special Problems in the Treatment of Depression." Psychiatric Times. Supplement June 1995.

Reynolds, Charles III. "Treatment of Depression in Late Life." Recent Advances in Assessment and Treatment. 1996.

Schneider, Lon. "Challenges in Treating Late-Life Depression" Psychiatric Times. January 1996.

Swedo, Susan and Leonard, Henrietta. "It's Not All in Your Head." HarperCollins Publishers, San Francisco. 1996.

Webster, Joy and Grossberg, George. "The New Antidepressants and the Elderly Psychiatric Patient" Psychiatric Times. October 1995.

Weiss, Kenneth J. "Management of Anxiety and Depression Syndromes in the Elderly." Journal of Clinical Psychiatry. February 1994.