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Antidepressant, Talk Therapy Fail to Beat Placebo



Neither antidepressants nor "talk therapy" were able to outperform inactive placebo pills in a new clinical trial on depression treatment -- though there were hints that the effects varied based on people's sex and race, researchers report.

The findings, published in the Journal of Clinical Psychiatry, add to evidence that people receiving "real" depression treatment in studies -- from antidepressants to St. John's wort -- often do no better than people given a placebo.

A recent review found that a minority of antidepressant users even fared worse than placebo users.

In this latest study, researchers randomly assigned 156 depression patients to either take the antidepressant sertraline (Zoloft and other brands) daily for 16 weeks; undergo a form of psychotherapy called supportive-expressive therapy (twice a week for four weeks, then weekly for 12 weeks); or be in a placebo group given inactive pills.

After 16 weeks, there were no overall differences in how the three groups fared.

Of antidepressant patients, 31 percent were treatment "responders" (meaning they'd fallen below a certain score on a standard measure of depression symptoms, or had seen their score drop at least 50 percent.)

The same was true of about 28 percent of patients in the talk-therapy group, and 24 percent in the placebo group. The differences among the three groups were so small as to be likely due to chance.

"I was surprised by the results. They weren't what I'd expected," said lead researcher Jacques P. Barber, dean of the Institute of Advanced Psychological Studies at Adelphi University in Garden City, New York.

Still, he stressed in an interview, the lack of benefit over placebo does not mean that depression therapies are pointless.

For one, Barber said, receiving a placebo in a clinical trial "is not the same as getting no treatment."

Study participants in placebo groups have contact with health professionals who are asking about their symptoms and well-being, Barber pointed out. And for some people, that attention can make a difference -- and may help explain the placebo response seen in studies.

In addition, at least some people in placebo groups believe they are getting the real treatment. And some studies have suggested that people's beliefs about their therapy play a key role in whether they get better.

But apart from that, different people may respond differently to a given type of depression therapy. Barber's team found some evidence of that.

The study, which focused on urban, low-income adults with major depression, had an unusually large minority population for a clinical trial on depression: Of the 156 patients, 45 percent were African American.

And Barber's team found that African-American men tended to improve more quickly with talk therapy than with medication or placebo.

In contrast, white men fared best on placebo, while black women showed no differences in their responses to the three treatments.

Only white women, Barber said, showed the expected pattern: a quicker response to both medication and talk therapy than to the placebo.

But all of that is based on fairly small numbers of people, and more research is needed to see if the gender and racial differences are real, according to Barber.

A psychiatrist not involved in the study agreed. "Those findings are interesting, but need to be interpreted with a grain of salt," said Dr. David Mischoulon, an associate professor of psychiatry at Harvard Medical School.

EVERYTHING WORKS TO SOME DEGREE?

As for the overall lack of benefit from the real treatments over placebo -- in this and other studies -- Mischoulon cautioned against reading that as "nothing works for depression."

"I think it's the opposite," he told Reuters Health, "It's more that, everything seems to work to some degree."

Like Barber, Mischoulon said that the placebo condition in clinical trials is not really "no treatment."

His advice for people suffering from depression symptoms is to talk with your doctor about the pros and cons of all the treatment options, including different forms of talk therapy and medication.

"I try to offer as broad a menu of options as possible, because all may potentially help," said Mischoulon, who has also studied alternative depression remedies, like fish oil and acupuncture.

Another caveat from the current study, he noted, is that it looked only at two types of medication. (Some patients were switched to another drug, venlafaxine (Effexor), if they did not respond to sertraline after eight weeks). And it tested just one type of talk therapy.

Supportive-expressive therapy is a short-term form of psychoanalysis that aims to help people understand how their personal relationships are related to their symptoms.

It's different from cognitive behavioral therapy, the best-studied form of talk therapy for depression. Both Barber and Mischoulon said it's not clear if the current findings would extend to psychotherapies other than supportive-expressive therapy.

"This is one type of psychotherapy, and it's two antidepressants," Mischoulon said. "It would be wrong to conclude that psychotherapy doesn't work, and antidepressants don't work."
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