The Nation: Side Effects; Your Zoloft Might Prevent a Heart Attack
By PETER D. KRAMER
Published: June 22, 2003
PATIENTS are beginning to treat depression with respect. Whether their doctors are ready to do so is less clear.
A study in the current issue of The Journal of the American Medical Association finds that almost six in 10 Americans who suffer depression seek treatment in a given year. A decade ago, the figure was one in three.
But the researchers found that only about 40 percent of patients received what standard guidelines consider ''minimally adequate medical treatment.'' Those criteria call for a month of antidepressants monitored in four office visits or eight half-hour counseling sessions.
There is a long tradition in general medicine of ignoring or undertreating depression. But a second article in JAMA suggested reasons that the pattern may change. That report described the largest study of psychotherapy ever conducted, sponsored by the National Heart, Lung and Blood Institute.
The study is a response to evidence, developed over the past decade, that depression, like diabetes and hypertension, is a risk to the heart. By middle age, studies show, depression triples or quadruples the risk of cardiac death. The most acute danger comes in the wake of heart attacks. After a first attack, depression raises the risk of recurrence dramatically -- between two- and fourfold.
The recent study enrolled about 1,800 patients who had suffered a heart attack in the past month and now met criteria for depression. Half the depressed patients received cognitive psychotherapy, a treatment aimed at reversing self-disparaging thoughts. The other half received ''usual care,'' without psychotherapy.
Despite the researchers' expectations, psychotherapy had no effect on the recurrence of heart attacks or on mortality. Therapy lowered the degree of depression early on; over time, the differences between the treatment and control groups vanished.
But hidden in the therapy trial results are suggestive findings about another standard intervention, antidepressants. For ethical reasons, if subjects had severe depression or if they failed to respond to psychotherapy, they were offered medication, principally Zoloft. By the end of the study, almost a quarter of the subjects had taken antidepressants for substantial periods of time.
Antidepressants were associated with an extraordinary reduction in death or heart attack recurrence -- 30 to 40 percent. The treatment assignment was not random, which makes the result hard to interpret. But it was the more depressed, less responsive group who had gotten medication.
If antidepressants reduce cardiac risk, how they do so remains unclear. The connection between depression and heart disease goes beyond neglect of one's health. Recent studies have shown that people suffering from depression have subtle problems with heart rate regulation. And it has long been known that their blood platelets can be ''sticky'' -- that is, likely to cause clots. The drugs used to treat depression by affecting the brain's use of the chemical serotonin -- Prozac, Paxil, Zoloft -- also tend to reduce the abnormalities in heart rhythm and blood clotting. For cardiac patients, these antidepressants may act primarily as blood thinners, a complicated form of baby aspirin.
However the drugs work, their role in treatment is becoming clear. Dr. Ranga K. Krishnan, chairman of psychiatry at Duke University and a consultant to the cardiac study, says that until contradicting data emerge, treatment with a medication like Zoloft is now the standard of care for patients with heart attacks accompanied by depression.
The relationship between cardiovascular disease and depression is especially intimate. Harm runs in both directions. Scans show that patients who develop depression late in life tend to have suffered ''silent strokes'' in parts of the brain that regulate mood. A region called the prefrontal cortex (just behind the forehead) is particularly implicated.
But depression extends into other realms of internal medicine. Chronic depressives may have enlarged adrenal glands, brittle bones and a diminished ability to fight off infections. Interferon -- a standard treatment for hepatitis C, some cancers and multiple sclerosis -- causes depression with high frequency. In one study, giving two weeks of Paxil before starting interferon cut the depression rate from 45 percent to 11 percent, with a corresponding decrease in the treatment dropout rate. Dr. Krishnan, believes that it is only a matter of time until large numbers of non-psychiatric doctors gain experience in treating depression.
Brain scans suggest that like silent strokes, interferon may exert its harm by impeding the workings of the prefrontal cortex. And it turns out that run-of-the-mill depression looks a good deal like these ''medical depressions.'' In autopsies of depressed patients, the brains show subtle disorganization in the prefrontal cortex.
No one expects the cause of depression to be located in one cortex of the brain. Psychiatric research is turning up anatomical differences in diverse regions that regulate emotion. Nor, despite the mixed showing in the JAMA study, has psychotherapy lost its role in treatment for depression.
But evidence from a number of quarters is making depression appear more ''medical'' -- the result and cause of concrete pathology in discrete parts of the brain and then throughout the body. The JAMA study finding that depression is treated inadequately suggests that family doctors have yet to adopt this view. The cardiac research hints that they may have to -- in which case, the cultural standing of depression may change as well. Depression may look ever less like a charming element in the artistic temperament and ever more like a progressive, systemic disease.
Drawing (Ray Vella)