April 25, 2000

Weighing Prozac, Once More

If the claims made by some researchers over the last few years are given any credence, the drugs, despite their popularity, are little better than dummy pills in driving away despair.

The critics insist that as much as 75 percent of the improvement shown by depressed patients taking antidepressants can be attributed to the "placebo effect," the healing power of taking a pill, any pill, and the support patients find in clinical trials. They say clinical trials of antidepressant medicines have been tainted by the pro-drug bias of the investigators conducting them.

But a recent report in The American Journal of Psychiatry offers a very different view. In it, a group of Columbia University scientists review the critics' evidence and find it far from convincing.

The studies cited by the critics "fail upon closer examination" to support their assertions, wrote the scientists, led by Dr. Fredric M. Quitkin, a professor in the department of therapeutics at Columbia's College of Physicians and Surgeons. And Dr. Donald F. Klein, a psychiatrist and co-author of the report, called claims that antidepressants are only slightly better than a placebo "a clear distortion."

"We are concerned that these conclusions may discourage depressed people from seeking effective treatment," Dr. Quitkin and his colleagues wrote.

It is true that teasing out the healing effects offered by a drug from the benefits bestowed by a dummy pill is a difficult task, particularly when the drug in question is intended to treat chronic illnesses like depression, arthritis or hypertension, whose symptoms worsen at some times and improve at others.

Complicating matters, depression, like most psychiatric illnesses, cannot be detected with blood tests and produces no changes in body tissue or other measurable physiological markers. Studies set up to test the efficacy of treatments for depression must rely upon more subjective measures: doctors' ratings or patients' own assessments.

The wiggle room left by such methods offers a perfect battleground for competing ideologies: those who believe, for example, that drugs are overused and promote psychotherapy as the treatment of choice for depression, versus those who see antidepressants as a lifesaving and underused resource.

The skeptics argue that even in the best studies, antidepressants are only minimally effective, and that doctors and patients often can tell, by the presence or absence of side effects, who is taking a drug, and who a placebo.

"Maybe 2 out of 10 people benefit," from taking antidepressants, said Dr. Roger Greenberg, a psychologist at the State University of New York Upstate Medical University at Syracuse, who has been among the most vocal critics.

In their review, however, Dr. Quitkin and his colleagues could find no evidence that bias accounted for the effects of the drugs shown in clinical trials.

Still, clinical trial investigators themselves are quick to concede that the measures used to assess subjects' progress are far from perfect.

"Emotions are not linear, and trying to measure something as complex as emotions on an arithmetic scale just becomes very difficult," said Dr. Arif Khan, the director of the Northwest Clinical Research Center in Bellevue, Wash.

In a paper appearing this month in Archives of General Psychiatry, Dr. Khan and two colleagues analyzed drug effects using clinical trial data from 7,315 patients participating in 45 studies of 7 antidepressants.

The researchers, who obtained clinical trial data from the Food and Drug Administration through a request under the Freedom of Information Act, found that of patients in the trials who received the antidepressants, 40.7 percent showed a reduction in symptoms. Of patients who received placebos, 30.9 percent improved.

Most studies have found larger effects. A 1999 study by the federal Agency for Health Care Policy and Research, for example, involving more than 80 trials of antidepressants, found that 50 percent of patients improved on the drugs, compared with 32 percent on placebos.

Dr. Khan called the effects of antidepressants in his study "modest," but he said he had no doubt that the drugs worked, particularly with severely ill patients who are normally excluded from trials. "When you go out in the real world and look at treated patients and untreated patients in Seattle or New York, believe me, the difference is very large," Dr. Khan said.

In the end, the clearest message of clinical trials may be that the drugs now available to treat depression are effective, but not effective enough.


By ERICA GOODE
Copyright 2000 The New York Times Company
"http://www.nytimes.com/library/national/science/health/042500hth-reflections.html"

janet paterson
53 now / 41 dx / 37 onset
a new voice: http://www.geocities.com/janet313/
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