A clinical trial of the popular herbal supplement St John's Wort which seems to suggest that it is no more effective than a placebo at treating depression has been slammed by dietary supplement associations in the US.
The trial, carried out by researchers at Duke University Medical Center, tested the efficacy of St. John's Wort against a placebo for the treatment of major depression. They also compared the herb with the antidepressant sertraline (also known as Zoloft).
The study was sponsored by the National Center for Complementary and Alternative Medicine (NCCAM), the NIMH and the Office of Dietary Supplements (ODS).
Some 340 people took part in the eight-week Duke study, divided into three groups receiving St John's Wort, sertraline or placebo. The initial treatment was followed by up to 18 weeks of continuation treatment in those participants who were responding favourably to medication at eight weeks. Patients were recruited from 12 academic or community clinics, and were all diagnosed with major depression.
What the researchers found was that there was apparently no evidence to show that St John's Wort, or indeed the antidepressant drug, was more effective than the placebo at treating depression.
"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," said Jonathan R.T. Davidson, director of the Anxiety and Traumatic Stress Program at Duke and principal investigator of the study, writing in the Journal of the American Medical Association (JAMA). "Rather than self-medicate with an over-the-counter medication or supplement, patients are strongly advised to consult an appropriate healthcare provider to assess the best treatment for a depressive episode."
Another author on the study, Robert Califf, director of the Duke Clinical Research Institute, emphasised the dangers of inadequate studies of St. John's Wort and other herbal remedies. "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," he said.
The researchers claimed that previous studies of the herb, performed largely in Europe and many of which had positive findings, had not clearly characterised the types of depression that might respond to the treatment.
"More people are turning to St John's Wort as a treatment for their depressive symptoms than ever before, and the majority of them do so without consulting a physician," said Davidson. "It is vitally important to conduct well-designed studies to examine herbal supplements and other drugs for the treatment of depression, which is a common and sometimes debilitating illness."
But it is not only the results of the study which have angered the herbal products industry - the researchers took the opportunity to warn against the excessive use of herbal products. "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.
"There are only two kinds of therapies - those that work and those that don't work. Until there is a reliable compound made from St. John's Wort that has demonstrated efficacy for treating depression, it is very important that people think twice about taking this drug," he added.
The St John's Wort extract used in the study was LI-160, manufactured by Lichtwer Pharma of Germany. It was selected because it is a well-characterised and well-studied extract of St John's Wort that had published literature supporting its possible efficacy in treating depression. The entire supply of St John's Wort extract used in the study came from one batch and was standardized to between 0.12 and 0.28 percent hypericin. Hypericin is thought to be one of the primary active ingredients in St John's Wort. The US herbal products industry was unanimous in its condemnation of the study's conclusions.
"This new research in no way invalidates the scores of clinical studies and analyses that have clearly demonstrated that St John's Wort is effective for mild to moderate depression," said Phil Harvey, director of science and quality assurance for the National Nutritional Foods Association (NNFA).
"In fact, contemporary researchers have found evidence that St John's Wort extracts are 'therapeutically equivalent to' and 'at least as effective as' some commonly prescribed antidepressant drugs. Research also indicates that people have better tolerance for the herb.
Harvey pointed out that the body of literature mentioned by the Duke researchers concerning the efficacy of St John's Wort focused almost entirely on mild to moderate depression. However, he said, the scientific literature has never supported the use of St. John's Wort for more severe forms of depression, such as those experienced by the subjects in the study.
"Therefore, this study neither supports nor invalidates the use of St John's Wort for the appropriate population - those mild to moderately depressed."
The NNFA was joined in its condemnation by the American Herbal Products Association (AHPA), whose vice president of scientific and technical affairs, Steven Dentali, called it "a quintessential case of the Emperor's New Clothes".
"It is inexplicable that JAMA has created such fanfare over the fact that St John's Wort is not shown to be effective for a condition that it was never intended to treat. The real story here is that if this study is believable it showed that a blockbuster drug, with sales of over $2 billion and prescribed to millions of Americans for severe forms of depression, may be no more effective than placebo."
The Council for Responsible Nutrition (CRN) called the report "misdirected and inconsequential," and accused the researchers of downplaying the fact that St John's Wort "did no worse than a known, effective antidepressant in the two most important primary outcome measures of the study".
John Cardellina, vice president, botanical science and regulatory affairs at the CRN, said: "This new report dismisses the scientific fact that St John's Wort has been proven safe and beneficial for the treatment of mild to moderate depression, stress and anxiety, according to a substantial body of evidence in the medical literature based on more than 30 controlled clinical studies and three meta-analyses or systematic reviews."
Other leading experts also questioned the usefulness of the research. "It is difficult to understand why NIH chose to study this type of patient population," said Jerry Cott, psychopharmacologist and former chief of the Psychopharmacology Research Program at the National Institute of Mental Health (NIMH).
"It appears that they enrolled a population of patients who were too depressed to respond to either sertraline or hypericin. If they had designed the study to focus on mild to moderate depression, then we would most likely have seen a very different result with both standard antidepressant and St John's Wort. The lack of response in the standard treatment (positive control) group prevents any valid conclusions from this study regarding the effectiveness of St John's Wort."
He continued: "This result is not uncommon in pharmaceutical industry-sponsored studies, though normally they are not published. The study simply lacked the sensitivity to detect a difference."