A

ANTIDEPRESSANTS

Depression in older adults is now being recognized as a severe and widespread health problem. Despite the availability of newer and safer antidepressants, depression is often unrecognized and undertreated in this population. Currently, there are several classes of antidepressants available for treatment of depression. They could be classified as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the miscellaneous group.

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) were the original antidepressants. MAOIs are very potent but more risky to use, particularly in older patients. MAOIs work by blocking the enzyme monoamine oxidase either reversibly or irreversibly. MAOIs that block the enzyme irreversibly are Iproniazid, Phenelzine, and Tranylcypromine. While taking these medications, patients have to avoid certain food products such as cheese (which contain higher levels of tyramine) as well as many over-the-counter cold medications. In combination with MAOIs these drug-food and drug-drug interactions may cause alarming increases in blood pressure and could be lethal. Since safer antidepressants are available now, these medications are seldom used.

Reversible inhibitors of monoamine oxidase, such as moclobemide and selegiline (only at lower doses) were introduced with the claim that they may not have the dangerous interactions like the irreversible MAOIs. Nonetheless, recent reports suggest that they should also be used very cautiously.

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants (TCAs) work by increasing the availability of the neurotransmitters norephinephrine and serotonin in the synaptic space between nerve cells in the brain. Until recently this group of antidepressants was the "gold standard" in the treatment of late-life depression and is still used as a standard to compare newer antidepressants. This group includes medication such as amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotyline, nortriptyline, protriptyline, and trimipramine. Medications in this group have been shown to slow conduction of electrical impulses in the heart and could be lethal if a patient were to overdose with them. The TCAs also have anticholinergic side effects (dry mouth, blurred vision, constipation, urinary retention, etc.) to which older patients are very sensitive and thus are not currently used as first-line medication for late-life depression. Despite this, nortriptyline is the best studied antidepressant for acute and continuation treatment of depression in older patients. If nortriptyline is used, it is essential that plasma concentrations be monitored, since there is a proven blood level range at which it is effective and safe. It is also recommended that the electrocardiogram (ECG) be assessed prior to starting and during treatment.

Common side effects of the TCAs include dry mouth, urinary retention, confusion, constipation, blurred vision, dizziness (may lead to falls and fractures), and sedation.

Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) act by increasing the concentration of serotonin available to nerve cells. Currently the most prescribed antidepressants in the world, this group includes of citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. The SSRIs are safer and better tolerated than MAOIs and TCAs. There is still some lingering controversy as to whether they are as potent as the older antidepressants for very severe depression. The SSRIs are generally not lethal in overdose, which is a significant benefit in the elderly depressed patients who are at the highest risk for suicide. The common side effects of SSRIs include nausea, vomiting, diarrhea, headaches, anxiety, sexual problems, and sleeplessness. Usually the side effects are temporary in nature. In elderly people, fluoxetine has been reported to cause some weight loss, agitation, and also stays in the body for a long time. Also, it should be noted that fluvoxamine is not approved by the FDA (Food and Drug Administration) for the treatment of depression. Medications in this group are also known to interact with other drugs often causing a reduced metabolic breakdown. Of the available SSRIs, citalopram and sertraline have relatively lesser drug interactions and are well tolerated in older people. These medications are also associated with some unusual side effects predominantly in elderly people. One such side effect is the decrease in sodium in the blood (hyponatremia). The other is the report of higher incidence of Parkinson's disease—like movement problems in elderly people. There have been some recent reports of falls in elderly patients even with the use of SSRIs (which were previously thought not to increase the risk of falls in the elderly when compared to TCAs).

Miscellaneous

There are other antidepressants that do not belong to the previous categories mentioned and are grouped together here.

There is some data showing that the antidepressant buproprion is effective in late-life depression. It is thought to work by increasing the amount of dopamine available to the brain nerve cells and hence may be an attractive alternative medication. It has few interactions with other medications and fewer sexual side effects compared to the SSRIs but there is some concern for seizures at higher doses.

Nefazodone works somewhat like the SSRIs, but also has some other specific pathways through which it acts. Limited information is available at this time about the effectiveness of this medication in late-life depression. It can cause some very serious drug interactions.

Venlafaxine works by increasing both norepinephrine and serotonin, as do the TCAs. However, it is much more selective than the TCAs in affecting other nerve systems, which contribute to side effects. Nonetheless increases in blood pressure and nausea may be significant problems for some patients when using this medication.

Mirtazapine works at multiple sites in the brain to induce its antidepressant effect. There is information that it may help older patients, particularly those at risk of significant weight loss. Mirtazapine does increase appetite and also causes sedation, which may actually be helpful for some older people.

Methylphenidate is not considered an antidepressant but is sometimes used for older depressed people who are significantly withdrawn and lack motivation. Therefore it may be particularly useful in older depressed people undergoing rehabilitation. Limited data is available for its effect in depression.

St. John's Wort, a popular herbal remedy for mild to moderate depression, has not yet been thoroughly evaluated in older adults. However, St. John's Wort has recently been found to cause important drug interactions for many medications commonly used in the elderly, such as digoxin.

LALITHKUMAR K. SOLAI BRUCE G. POLLOCK

See also DEPRESSION; ELECTROCONVULSIVE THERAPY; INTERPERSONAL THERAPY; PROBLEM SOLVING THERAPY.

BIBLIOGRAPHY

DUNNER, D. L. "Therapeutic Consideration in Treating Depression in the Elderly." Journal of Clinical Psychiatry 55 (1994): 48–57.

GEORGOTAS, A.; MCCUE, R. E.; HAPWORTH, W.; FRIEDMAN, E.; KIM, M.; WELKOWITZ, J.; CHANG, I.; and COOPER, T. B. "Comparative Efficacy and Safety of MAOIs Versus TCAs in Treating Depression in the Elderly." Biological Psychiatry 21 (1986): 1155–1166.

GLASSMAN, A. H., and ROOSE, S. P. "Risks of Antidepressants in the Elderly: Tricyclic Antidepressants and Arrhythmia-Revising Risks." Gerontology 40 (1994): 15–20.

LEBOWITZ, B. D.; PEARSON, J. L.; SCHNEIDER, L. S.; REYNOLDSIII, C. F.; ALEXOPOULOS, G. S.; BRUCE, M. L.; CONWELL, Y.; KATZ, I. R.; MEYERS, B. S.; MORRISON, M. F.; MOSSEY, J.; NIEDEREHE, G.; and PARMELEE, P. "Diagnosis and Treatment of Depression in Late Life: Consensus Statement Update." Journal of the American Medical Association 278 (1997): 1186–1190.

LEO, R. J. "Movement Disorders Associated with the Serotonin Selective Reuptake Inhibitors." Journal of Clinical Psychiatry 57 (1996): 449–454.

NEWHOUSE, P. A. "Use of Selective Serotonin Reuptake Inhibitors in Geriatric Depression." Journal of Clinical Psychiatry 57 (1996): 12–22.

REYNOLDSIII, C. F.; FRANK, E.; PEREL, J. M.; MAZUMDAR, S.; and KUPFER, D. J. "Maintenance Therapies for Late-Life Recurrent Major Depression: Research and Review Circa." International Psychogeriatrics 7 (1995): 27–39.

RICHELSON, E. "Synaptic Effects of Antidepressants." Journal of Clinical Psychopharmacology 16 (1996): 1–9.

SCHNEIDER, L. S. "Pharmacological Considerations in the Treatment of Late-Life Depression." American Journal of Geriatric Psychiatry 4 (1996): 51–65.

SOLAI, L. K.; MULSANT, B. H.; and POLLOCK, B. G. "Update on the Treatment of Late-Life Depression." In The Psychiatric Clinics of North America—Annual of Drug Therapy. Edited by David L. Dunner and J. F. Rosenbaum. Philadelphia: W. B. Saunders Co., 1999: Pages 73–92.

THAPA, P. B.; GIDEON, P.; COST, T. W.; MILAM, A. B.; and RAY, W. A. "Antidepressants and the Risk of Falls among Nursing Home Residents." New England Journal of Medicine 339 (1998): 875–882.