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Herbs, drugs and severe depression

A new study found placebo to be more effective than either St. John’s Wort or the popular anti-depressant Zoloft in providing relief to severely depressed patients.
Millions of Americans take St. John's wort for depression, but a new study questions the herb's effectiveness. NBC's Robert Bazell reports.
Millions of Americans take St. John's wort for depression, but a new study questions the herb's effectiveness. NBC's Robert Bazell reports.
/ Source: staff and news service reports

A sugar pill was more effective than either St. John’s Wort or the antidepressant Zoloft in providing relief to severely depressed patients, according to a new study that is unlikely to end the debate about the role of the popular supplement in treating the disorder.

In the study, depression improved after eight weeks in 32 percent of patients treated with a placebo, versus 24 percent of those taking St. John’s wort and 25 percent treated with Zoloft, an antidepressant in the Prozac family. The trial enrolled 340 patients with major depression.

The National Institutes of Health funded the work after a 1996 meta-analysis of 23 studies involving 1,757 people showed that Hypericum, the active ingredient in St. John’s wort, may be effective for mild to moderate depression. Many doctors said that the 23 studies, mostly done in Europe, were insufficient from which to draw firm conclusions.

Many of the trials used different preparations, which contained varying amounts of the active ingredient in the weed with bright yellow flowers known as St. Johns’ wort, they said. And, they added, many of the studies were too short, or had too few people, to be conclusive.

But instead of ending the debate, the new study, which will be published in this week’s Journal of the American Medical Association, stirred more controversy.

The confounding results show the difficulties in examining the effectiveness of various remedies for severe depression, said John Cardellina of the Council for Responsible Nutrition, a trade group representing herbal remedies and supplements.

In order for the study to be instructive, the group of patients taking Zoloft would need to improve beyond those taking a sugar pill, or placebo, he said.

“You can’t claim St. John’s wort is ineffective based on this trial, because Zoloft was also ineffective,” said Cardellina, who was not involved in the study.

“The study falls into the one third of clinical trials on depression where the active ingredient didn’t work,” concurred Steven Dentali, vice president of scientific and technical affairs for the American Herbal Products Association, another trade group. “The trial is underpowered,” he said, meaning that it was either too short or enrolled too few people to show benefit.

But the study’s lead author Dr. Jonathan Davidson of Duke University noted that Zoloft did produce improvements on a secondary scale measuring the symptoms of depression, while St. John’s wort did not.

Another explanation for why Zoloft did not work better is that the dose prescribed was too low, he said.

“Major depression is treatable, but this research suggests that major depression of at least moderate severity should not be treated with St. John’s wort,” Davidson said.

“Rather than self-medicate with an over-the-counter medication or supplement, patients are strongly advised to consult an appropriate health care provider to assess the best treatment for a depressive episode,” he said.

Another problem
Another problem, critics said, is that St. John’s wort was never recommended for the severe depression suffered by patients in the trial.

St. John’s wort is indicated for mild depression, “on the order of heightening mood when you have the blues,” said Dentali. “St. John’s wort was not meant to supplant the use of drugs for serious depression.”

But Robert Califf, director of the Duke Clinical Research Institute and another author of the study, said, “As long as these types of products remain available to the public without the protection of adequate, controlled and unbiased studies, taking them is like playing Russian roulette with your health.

“Just because St. John’s wort was found to be ineffective for this type of depression does not mean it is harmless to the body,” said Califf. “Several studies have shown that St. John’s wort interacts dangerously with several medications such as those used to treat HIV/AIDS, certain cardiac conditions and even those that keep the body from rejecting organs after transplant.”

In the study, St. John’s wort was generally well tolerated, though people who were taking the extract did experience more sexual dysfunction, general swelling and urinary frequency than those taking placebo. Side effects associated with Zoloft sexual dysfunction, sweating, nausea and diarrhea.

The NIH is now planning to conduct a study of the effectiveness and safety of St. John’s wort in patients with minor depression.

But until thsoe results are in, Cardellina said he was concerned that the study will be misinterpreted as condemning St. John’s wort as researchers take sides in the ongoing controversy in the American medical community about the herbal remedy. “The interpretation of the results of the study is going to be confusing,” he said.

Reuters contributed to this story.