Keeping Up with CAM

The Lure of Herbal Medicines Continues to Grow

By Rebekah McCallister

SAN DIEGO—Over the past 15 years, huge progress has been made in 2 aspects of complementary and alternative medicine (CAM), Barak Gaster, MD, said at the American College of Physicians annual meeting. These are (1) the increasing number of patients who are using CAM, and (2) the explosion of good research conducted in this area.

Barak Gaster, PhD

"This is not something that people are just dabbling in," said Dr Gaster, associate professor of medicine, University of Washington School of Medicine, Seattle. "This is something that people are interested in, experimenting with, and—to a pretty large extent—sticking with."

Acupuncture for Osteoarthritis

Take acupuncture, for example. About 1% of the American public has used acupuncture in the past 12 months, and 4% have used it at some time in their lives, statistics that Dr Gaster considers "astounding," and ones that no one would have believed 15 years ago.

The tricky part about acupuncture, Dr Gaster says, is that traditional Chinese medicine practitioners almost never use acupuncture by itself but rather use it in combination with a complex mixture of traditional herbs that are nearly impossible to recreate. And it is this use of complicated herbal prescriptions that can be a difficult concept for Western practitioners to understand.

"These are centuries-old formulas, with 6 to 12 different herbs mixed together. The way that we are taught to practice Western medicine is that you don't want to add too many medicines at once, it's better to add things one at a time, whereas the Chinese approach is based on symptoms and physical exam findings. And so each individual is going to get a slightly different prescription," he said.

This is one of the main reasons why Western researchers have taken acupuncture out of the traditional system and studied it in isolation.

The best evidence that acupuncture does, in fact, work is in patients with osteoarthritis (OA). This was demonstrated in the best and most rigorous study of acupuncture to date (Ann Intern Med. 2004;141:901-910). This large, randomized study included a diverse group of 570 patients, all of whom had OA of the knee. The patients were randomized into 3 arms: true acupuncture, sham acupuncture, or an education-only group that served as controls. All the patients received treatment for 2 months and were then followed up for 6 months.

"The first thing that really pops out is how much better the sham acupuncture was compared with the control group," Dr Gaster said. "It shows what we have all suspected and known for years, which is that the placebo effect from acupuncture is huge."

However, the big headline from this trial was that the patients who received true acupuncture reported much greater improvement than those who received sham acupuncture. "People who got true acupuncture in a truly blinded way did statistically better than the people who got sham acupuncture," Dr Gaster said. "So this is the first solid, good evidence we have that acupuncture works."

Acupuncture for other conditions is more of a dicey story, he says. The other 3 well-done, randomized, controlled trials have demonstrated that acupuncture is not effective for fibromyalgia (Ann Intern Med. 2005;143:10-19) or migraine headache (JAMA. 2005;293: 2118-2125), and, while it may mildly reduce neck pain, the results were not clinically significant (Ann Intern Med. 2004;141:911-919).

Take-home message:

• Good evidence has now demonstrated that patients with OA feel better with acupuncture
• Well-blinded sham acupuncture studies provide some evidence that the benefits of acupuncture may be more than a placebo effect.

St. John's Wort for Depression

St. John's wort is the "poster child of herbal medicine," says Dr Gaster. When CAM use in the United States was first exploding in the mid-1990s, St. John's wort was the number-one herb used. Since then it has been the most often prescribed antidepressant in Germany.

The pharmacology of St. John's wort is complicated. It contains more than 5 substances that have invitro activity against the standard neurotransmitter that is believed to be involved in depression. At one time, hypericin was thought to be the most active ingredient, but growing evidence suggests that hyperforin may be a more active component, Dr Gaster reports.

A large number of European trials have demonstrated positive results for St. John's wort. However, negative findings have been reported in 2 large US trials (JAMA. 2002;287:1807-1814; 2001;285:1978-1986).

Dr Gaster notes that the degree of baseline depression in the US trials was much more severe than in the European trials. "For that reason I think we can somewhat reconcile these data and say St. John's wort is maybe an effective antidepressant in people who have quite mild depression," he says.

St. John's wort is well tolerated, with very few side effects, but it does have the potential to interact adversely with many other drugs, including immunosuppressants, protease inhibitors, statins, steroids, and calcium channel blockers.

Take-home message:

• St. John's wort may be effective for mild depression, but no good data are available for its efficacy for severe depression
• It has the potential to adversely interact with many common drugs.

Ginkgo Biloba: Jury Still Out

Although ginkgo biloba is now the most frequently used herbal medicine in the United States, very few clinical studies have been conducted. A few trials have shown some modest benefit versus placebo in patients with dementia, but the benefits have been small and similar to the small effect seen with cholinesterase inhibitors, such as donepezil (Aricept). And some studies have shown negative results.

Still, the millions of people who are using ginkgo do not have dementia, Dr Gaster pointed out. They are middle-aged and elderly people who are worried that they are going to get dementia.

In 2000, the National Institutes of Health (NIH) funded a 5-year, placebo- controlled, randomized trial of >3000 patients (aged ≥75 years) to test ginkgo's efficacy for the prevention of dementia. Results are expected in 1 to 2 years.

Ginkgo is very well tolerated overall; rarely patients report gastrointestinal upset, headache, or dizziness. The most important safety issue is that this herb can cause bleeding; dozens of case reports describe people with cerebral hemorrhages associated with ginkgo consumption, says Dr Gaster.

"It's definitely wise to avoid using ginkgo in combination with other drugs that can cause bleeding, like warfarin or aspirin, and patients should definitely stop taking ginkgo at least 7 days prior to surgery," he says.

Take-home message:

• Ginkgo biloba may be moderately effective for dementia, but data are limited, and inconsistent; NIH results are expected in 1 to 2 years
• Improvement is similar to that with donepezil
• Ginkgo is much cheaper than donepezil (annual cost: $200 vs $2000)
• Warn patients about possible bleeding; they should avoid using it when taking aspirin or warfarin and before surgery.

Glucosamine and Chondroitin

Glucosamine and chondroitin are substrates for the production of articular cartilage. Glucosamine products are generally made from the shells of crabs and other shellfish; chondroitin is made from cow or shark cartilage.

Until recently, the largest study for glucosamine and chondroitin was a 3-year controlled trial that was centered in Belgium (Lancet. 2001;357:251-256). A total of 212 patients with OA of the knee were randomized to 1500 mg/day of glucosamine sulfate or to placebo. Primary outcomes were patients' Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and mean joint-space narrowing on x-ray.

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Dramatic positive results were seen with glucosamine over placebo, in terms of WOMAC score (pain: = .047; function: = .020) and joint-space narrowing ( = .04).

"This is the first suggestion that we have a disease-modifying therapy for OA," Dr Gaster said. "This is a tantalizing finding."

However, results published last year from the large NIH-funded Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) (N Engl J Med. 2006;354: 795-808) contradicted these findings, demonstrating that neither glucosamine nor chondroitin works for OA. (See IMWR, January 2006 & April 2006.)

Although overall pain reduction of patients with OA of the knee in all patients was not significantly greater with either glucosamine or with chondroitin than with placebo, "If you look at the subset of patients who had moderate-to-severe pain at baseline who got the combination of glucosamine and chondroitin, they were significantly better than the people who got placebo," Dr Gaster points out.

"This is really the first clinical trial data that we have that these 2 agents work synergistically together," he added.

More data from this trial are expected. About half of the GAIT patients are being followed for 2 years. In addition to longer-term outcomes, this follow-up will provide data on the effects on radiographic joint-space narrowing.

For now, glucosamine and chondroitin are both very safe and well tolerated, with few side effects and no reported drug interactions.

Take-home message:

• Glucosamine and chondroitin may be effective, especially in more severe disease
• The combination of both seems to work best
• Treatment can be expensive ($25-$75/month).