June 13, 2002 -- Antidepressant medications are some of the most widely advertised and widely prescribed drugs in the country. But there's growing evidence that placebos — sugar pills — can often be just as effective at improving mood, and can even improve brain chemistry.

When Americans complain to their doctors about being depressed, the vast majority, 90 percent, are given antidepressants, drugs such as Prozac or Zoloft or Paxil. And while these medications can help relieve depression, clinical trials show that many patients also get better from a simple sugar pill.

"They [patients] don't know whether it's the active medication or the sugar pill but they have a belief that the medication may help and that can contribute to their improvement," Dr. Timothy Walsh, a psychiatrist at Columbia University in New York, told World News Tonight's John McKenzie.

The Placebo Effect

The phenomenon of seeing an improvement while taking a placebo is known as the placebo effect, and is well-known in the field of psychiatry.

For example, a recent study published in the Journal of the American Medical Association designed to test the efficacy of the herbal remedy St. John's Wort compared the herb to a placebo as well as Zoloft.

St. John's Wort didn't perform significantly better than the placebo — but neither did Zoloft. And experts say that this isn't an uncommon occurrence with antidepressant medications.

Dr. Arif Khan, medical director of the Northwest Clinical Research Center in Bellevue, Wash., who does testing for drug companies, analyzed 96 antidepressant trials from a 17-year period. He found that in 52 percent of the trials, there was no significant difference between the placebo and the medication.

"The differences would be like 7 or 8 percent in symptom reduction, which meant the difference was not large enough to be scientifically meaningful," he said.

Khan says most drug companies ran five or more trials to get two showing a significant benefit of a medication over a placebo — the current Food and Drug Administration requirement for approval.

The Power of Belief

Some researchers have stated that the placebo effect accounts for 100 percent of the benefits seen with antidepressant medications. While many don't go that far, some experts feel that the importance of the effect should not be diminished.

"The placebo effect has been inappropriately dissed for 50 years, rather than being honored and cultivated," says Dr. J. Alexander Bodkin, director of the clinical psychopharmacology research program at McLean Hospital in Belmont, Mass. "It has even been dismissed as being observer bias rather than a genuine therapeutic process."

New research may well be changing the way placebos — especially in the context of clinical trials — are viewed.

Two studies published earlier this year in the American Journal of Psychiatry, found that taking a placebo actually affected brain function and improved mood, much like drugs do. These changes were unexpected because placebo was thought to be an inactive treatment condition.

However, there was one important caveat to these findings.

"It seems they had to believe that they were getting medication in order to feel better," says Dr. Andrew Leuchter, lead author of one of the papers and director of adult psychiatry at the University of California, Los Angeles, Neuropsychiatric Institute and Hospital. "When we told the placebo subjects they had been on placebo, their mood deteriorated, in many cases very rapidly."

A Treatment Option?

Because withholding information is a key component to guaranteeing the success while a patient is on a placebo, it seems unlikely that it will be used for the active treatment of depression.

"Placebo as a treatment is not done anymore. Because of our current patient-centered ethics and because of the rejection of paternalism in medicine in general, it's no longer socially acceptable. I think that a great deal has been lost. A lot of good that can be done is placebogenic good," says Bodkin.

However, there is much that can be learned from understanding why placebos may be working. The findings of this research shed some light on the power of interpersonal contact and therapy when treating depression.

"The fact that [the subjects] came into treatment and went through all of the different components of the research milieu … including the interpersonal contacts, changed their brain function," says Leuchter of his study. "[There are many] factors that go into engendering the placebo response. Which of those are critical, we do not yet know."