Is alternative medicine poised for hospital formularies?

Standards, acceptance, and patient numbers are growing

The first U.S. multicenter clinical trial of a botanical alternative medicine, set to begin this summer to test the efficacy of St. John’s wort as a treatment for depression, is the first step toward the scientific status of an herbal product becoming a prescription drug in the United States, a status St. John’s wort already has achieved in Europe.

For hospital pharmacists, the news signals the integration of alternative medicine with the mainstream of the profession, where drug interactions, patient questions, and acceptance levels by the industry have already become issues. (For more information on the impact of alternative medicine, see the April 1998 issue of Drug Utilization Review.) Along with the advent of clinical trials, evidence that herbals could one day become part of a hospital’s floor stock or an agenda item with the pharmacy and therapeutics committee is growing. Recent surveys of physicians and consumers show that professional referrals and popular acceptance are climbing, all while sales are increasing dramatically. That has caused drug makers to introduce new herbal lines this year, while the National Institutes of Health Office of Dietary Supplements is working to make scientific information available, and the Federal Trade Commission is fine-tuning its regulatory oversight on a host of remedies that carry no FDA approval process.

The St. John’s wort trial will randomly assign the herbal (Hypericum perforatum), a placebo, or the antidepressant Zoloft (sertraline) in a six-month study funded by the National Institutes of Health Center for Complementary and Alternative Medicine.

"Research conducted in Europe suggests St. John’s wort has the potential to relieve depression without some of the side effects of pharmaceutical antidepressants, but still, the botanical’s own side effects must be rigorously evaluated as well as its true effect on mood," says Jeffrey Kelsey, MD, PhD, assistant professor of psychiatry and behavioral sciences at Emory University in Atlanta, one of 12 sites selected to conduct the St. John’s wort clinical trial.

Professionals like Kelsey are calling for such trials as a way to bring about standard scientific knowledge of herbals no matter what their future status because millions of consumers are using them regardless. At the same time, trials could help flatten out the learning curve for hospital pharmacists by giving them credible information.

Researchers believe that hypericum extract inhibits the reuptake of serotonin and other neurotransmitters similar to prescription selective serotonin reuptake inhibitors. What’s still unclear is the mechanism of action and the specific concentrations of the herbal that provide positive results.

According to the publication OTC Update, U.S. sales of St. John’s wort grew from $5 million in 1995 to $89 million just two years later. Similarly, sales for another popular herbal, ginkgo biloba, went from $85 million to $130 million in one year’s time. This year the regulatory oversight that does exist for the herbals market tightened. New labeling regulations that went into effect in March require herbal manufacturers to list the nutrient content of their products. That rule stems from the Congressional Dietary Supplement Health & Education Act of 1994. The act also gave the FDA power to take herbal products off the shelves if safety or post-market circumstances warrant it, but the agency has no scientific approval capabilities as it does with prescription drugs.

Instead, the Federal Trade Commission is the largest overseer of the botanicals market, largely addressing issues of advertising and labeling claims.

Also this year, the FTC refined and reissued its set of advertising regulations, titled A Guide for the Dietary Supplement Industry. The guidelines cover the disclosure of a product’s adverse effects, ensures that ads and labels disclose the limits of scientific research done on a product, frames the uses of anecdotal evidence, and even stipulates the labeling jargon in terms of what a product "may" do or "help" achieve, which is commonly used by manufacturers. (To see the entire set of guidelines, check out the FTC’s Web site at www.ftc.gov/bcp/conline/pubs/ buspubs/dietsupp.htm.)

Says Marcia Angell, MD, executive editor of the New England Journal of Medicine, "There cannot be two kinds of medicine, conventional and alternative, only medicine that has been adequately tested or has not, medicine that works or may not work. Once a treatment has been tested rigorously it no longer matters whether it was considered alternative, but it is time for the scientific community to stop giving alternative medicine a free ride."

Drug makers going herbal

Aware that market share is climbing, pharmaceutical companies are not waiting for exhaustive clinical trial results to get into the alternative marketplace. Last year, Warner-Lambert jumped first with its Halls Zinc Defense and Celestial Seasonings Herbal Comfort with Echinacea. This year the company is tapping into two of the most popular supplements with its Quanterra line, highlighted by Quanterra Mental Sharpness, a ginkgo biloba supplement, and Quanterra Prostate from saw palmetto.

Warner-Lambert is using the same carefully worded marketing for the products, which are not tested or regulated by the FDA, but are overseen for advertising content by the Federal Trade Commission to assure no specific medicinal claims are made. Packaging for Warner’s ginkgo supplement speaks to the promotion and maintenance of mental sharpness and blood circulation to the brain and extremities, both standard promotions for the product.

The company’s saw palmetto offering "helps to maintain healthy urinary flow and supports male prostate health," says Warner-Lambert’s David Barber. He notes that Warner-Lambert is also attempting to help its traditional industry associates, namely pharmacists and physicians, keep up with their homework on alternative medicine. "We are making a significant commitment to education, and we’ve already assembled an advisory board across conventional areas of medicine as well as leaders in herbal supplements."

American Home Products is also entering the herbal market with a line of six products called Centrum Herbals that includes ginkgo, saw palmetto, St. John’s wort, echinacea, garlic, and ginseng offerings.

The company is co-marketing with the Pharma Print Corp., which has patented a technology that measures herbal molecular levels to promote specific biological activity and therefore product marketing, which the company says is aimed at furthering scientific standards for the unregulated products. Another large and "traditional" drug maker, Bayer Corp., has also entered the market with a line of One-A-Day Specialized Supplements, while Herbs for Kids, a start-up company based in Bozeman, MT, is offering a line of 31 liquid herbal extracts for children ages 1 and up that also includes St. John’s wort and echinacea among its products, as well as white pond lilly, goldenseal, dong quai and chaparral.

More doctors are recommending alternative remedies and more consumers are using them, according to recent surveys. Late last year, the American Academy of Family Physicians published a survey that found one in three physicians recommend herbals to their patients at least once a week, while one in four doctors use the products themselves. The leading product physicians are recommending is St. John’s wort, according to the survey, followed by ginkgo biloba. Among consumers, nearly 70% say they use alternative medicines when traditional prescriptions have not cured them, according to a poll conducted by the Stanford University Center for Research in Disease Prevention.

Forty-nine percent said they’ve detected positive results from the use of herbals and supplements, while 65% said they use the products primarily for prevention. In terms of overall use, 81% said they have used some sort of alternative therapy, ranging from herbals to chiropractors, at some point in their lives.

A similar poll conducted this year by the National Consumers League states that 64% of those queried had taken vitamins in the last 12 months, 39% had taken herbal supplements and 21% had taken mineral supplements. Respondents were also asked if they agreed with a series of statements, from which 46% agreed that herbal supplements are generally safe, 37% found them effective in maintaining overall health and well-being, 36% agreed they were effective in preventing some diseases, 29% thought the products a good value, and 23% agreed they were as effective as prescription or OTC drugs.

For more information on the St. John’s wort trial, contact the Wesley Woods Health Center at Emory University, (404) 727-8968.