Treating Depression in the Medically Ill: These Patients Are Sensitive to Side Effects, May Be Taking Drugs That Can Interact with Antidepressants

By Sherman, Carl | Clinical Psychiatry News, November 2004 | Go to article overview

Treating Depression in the Medically Ill: These Patients Are Sensitive to Side Effects, May Be Taking Drugs That Can Interact with Antidepressants


Sherman, Carl, Clinical Psychiatry News


Depression and medical illness are frequent fellow travelers. Not only is the mood disorder more prevalent among people with chronic medical conditions than it is in the general population, but comorbidity complicates treatment, worsens response to antidepressants, and makes relapse more likely.

"Some patients are undertreated; others overtreated," said Steven L. Dubovsky, M.D., professor and chair of the department of psychiatry, State University of New York at Buffalo. Many illnesses produce depressionlike symptoms--low energy, loss of interest, sleep disturbance, depressed mood--that may resolve with appropriate medical treatment alone.

A focus on specifics may clarify the situation. "Distinguish hopelessness from resignation. A person with a terminal illness may be resigned but still hopeful of accomplishing important goals," Dr. Dubovsky said. Weakness is not anhedonia; even a sick person can respond positively to interactions with other people.

It is perhaps more common to discount true depressive symptoms on the assumption that they represent a natural response to being sick.

"The majority of people with even severe illness may be sad or angry, but they are not depressed," said Dan V. Iosifescu, M.D., director of neurophysiology studies in the depression clinical and research program, Massachusetts General Hospital, Boston.

When they do diagnose depression, clinicians are likely to "step gingerly" around patients perceived to be physically fragile. "The medically ill are treated for depression less often, and receive lower doses of antidepressants, but in fact they may need more aggressive treatment," he said.

In a recent study of depressed outpatients, Dr. Iosifescu and his associates found less treatment success in the context of illness: Fluoxetine response rates declined as the number and severity of medical conditions rose (Am. J. Psychiatry 2003;160:2122-7).

Illness did not need to be severe to affect outcome. The study participants' medical problems--including hypertension, diabetes, hypercholesteremia, and arthritis--were well controlled. "These were typical patients who might walk into a psychiatric practice," Dr. Iosifescu said.

Depression treatment should take comorbid illness into account. "There are two broad issues," Dr. Dubovsky said. "These patients are more sensitive than others to medication side effects, and they may be taking other drugs that can interact with an antidepressant."

Such interactions most often involve cytochrome P450 enzymes. Coumadin is a cytochrome P450 2D4 substrate, for example, and the risk of bleeding may increase if patients are given a drug that inhibits 2D4, such as fluoxetine or paroxetine (Paxil). Fluvoxamine (Luvox) will inhibit the metabolism of digitalis, a 34A substrate.

Because citalopram (Celexa) and escitalopram (Lexapro) have little cytochrome P450 activity, they are less likely to be troublesome in the context of other drugs, he said.

Sensitivity to antidepressant side effects argues for a lower initial dosage and more cautious titration than would be the case with a healthy patient, Dr. Dubovsky said. The choice of drug should take into account the bodily systems that are affected by the illness.

A tricyclic antidepressant might be an unwise choice for a patient with a recent MI, for example, because of the risk of adverse cardiac effects. A monoamine oxidase inhibitor might be the safest option for an individual with epilepsy because, unlike bupropion, it does not lower the seizure threshold, he said. …

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