Editorials calling for more and better studies of alternative medicine treatments appeared in the Sept. 17, 1998, issue of the New England Journal of Medicine and the Nov. 11, 1998, issue of the Journal of the American Medical Association (JAMA) (Angell and Kassirer, 1998; Fontanarosa and Lundberg, 1998; Jonas, 1998).
Alternative medicine was the theme of this issue of JAMA and in each of the other nine American Medical Association journals published in November, including the Archives of General Psychiatry and the Archives of Neurology.
The coordinated theme issues of the AMA represented, according to JAMA editors George D. Lundberg, M.D., and Phil B. Fontanarosa, M.D., "concerted effort by the editors of these scientific journals to...[provide] physicians and other health care professionals with clinically relevant, reliable, fresh scientific information on alternative therapies."
They rejected the notion that alternative medicine warrants alternative methods of validation, arguing that medicine, whether mainstream or unconventional, must either be adequately evaluated or considered unproved (Fontanarosa and Lundberg, 1998).
In the New England Journal editorial, Marcia Angell, M.D., and Jerome P. Kassirer, M.D., noted that while both conventional and alternative medicine make use of anecdotal case reports, the reports in conventional medicine are typically well-documented occurrences in defined settings, appear in peer-reviewed publications and yield hypotheses for testing in subsequent clinical trials. In contrast, Angell and Kassirer said, anecdotes about alternative medicine remedies are often published in lay magazines and books-with no informed, critical review. They have no comparable documentation or defined settings, "and are considered sufficient in themselves as support for therapeutic claims."
Specifically, these medical editors pointed to the fact that these treatments do not undergo scrutiny before becoming widely and enthusiastically accepted in the general population as safe, healthful, remedial and restorative.
The JAMA issue included the follow-up of a 1990 national survey of alternative medicine prevalence, costs and usage patterns. According to the study, the 629 million visits to alternative medicine practitioners in 1997 exceeded total visits to primary care physicians by an estimated 243 million. Additionally, while 33.8% of the adult population in the United States (60 million people) used at least one of 16 alternative therapies in 1990, that percentage increased to 42.1% (83 million people) in 1997 (Eisenberg et al., 1998).
David M. Eisenberg, M.D., and his colleagues at both the Center for Alternative Medicine Research and Education at Beth Israel Deaconess Medical Center in Boston, and the department of health care policy at Harvard Medical School, also determined that use of herbal remedies in the United States increased by 380% and the use of high-dose vitamins increased by 130% between 1990 and 1997. They extrapolated that nearly one in five individuals taking prescription medications are also taking such "nutraceuticals," and warned, "an estimated 15 million adults are at risk for potential adverse interactions involving prescription medications and herbs or high-dose vitamin supplements." (See "Herbal Medicines Pose Potential Drug Interaction Hazard," Psychiatric Times August 1998, p 62.)
This proliferation of alternative medicine has not been without some progress in deliberate and systematic assessment of the products and practices, however. The Office of Alternative Medicine (OAM) at the National Institutes of Health (NIH) has been upgraded to the National Center for Complementary and Alternative Medicine and given increased funding for research trials (see "National Center For Alternative Medicine Established" in this issue). In 1996, the OAM funded a "complementary medicine" field within the Cochrane Collaboration, a multidisciplinary project that produces, maintains and disseminates systematic reviews on health care topics. Two major products of the Cochrane Collaboration are a database of systematic reviews and the Cochrane Controlled Trials Registry. Both databases are updated quarterly, with information added regularly by the complementary medicine field. By mid-1998, the Cochrane Complementary Medicine Trials Registry contained more than 3,500 randomized, controlled trials (Ezzo et al., 1998).
Several member agencies of the NIH collaborated on an international workshop, "Evaluating Research Needs on the Use and Safety of Medicinal Herbs," conducted at the National Institute of Environmental Health Sciences (NIEHS) conference facilities in Raleigh, N.C., in September 1998. In addition to the NIEHS, the workshop sponsors were the Office of Dietary Supplements, Office of Research on Women's Health, the Department of Health and Human Services' National Toxicology Program and Office of Disease Prevention and Health Promotion, the U.S. Food and Drug Administration's Office of Special Nutrition, and the Society for the Advancement of Women's Health Research.
Chief among the workshop topics were the changes to the Dietary Supplement Health and Education Act of 1994, proposed by the FDA (April 29, 1998), to modify allowable health claims for these products. Current interpretation of this act allows claims for effects on body structure and function, but not on disease. The proposed rule would preclude much of the structure and function claims, in addition to effects on disease, in the absence of evidence that meets the stringent FDA requirements imposed on pharmaceuticals (Mitka, 1998).
The JAMA correspondent at the workshop, Mike Mitka, reported that the critics of medicinal herbs argued that there wasn't enough efficacy and safety research on these products, while advocates argued "that the research was out there but in places that traditionally are overlooked."
The American Medical Association has made a prodigious effort in looking for the research in alternative medicine, and showcasing it in
the theme issues of its 10 journals. From the call for papers, more than 200 submissions yielded 80 articles and editorials on 30 different topics from 16 countries. These included 18 randomized trials and systematic reviews.
One such review by Edzard Ernst, M.D., Ph.D., and colleagues in the November Archives of General Psychiatry considered the available evidence supporting "complementary and alternative" therapies in the treatment of depression (Ernst et al., 1998). While they found very limited rigorous scientific data to support any regimen, the most evidence of benefit was found for exercise, herbal therapy with Hypericum perforatum (St. John's wort) and, to a lesser extent, for acupuncture and relaxation therapies.
In the Archives of Neurology, Barry Oken, M.D., and colleagues reviewed evidence for the efficacy of Ginkgo biloba on the cognitive function of patients with Alzheimer's disease. Of more than 50 articles identified in an English and non-English language literature search, only four studies met the reviewers' criteria for inclusion in a meta-analysis. In their analysis of the effect of Ginkgo biloba or placebo on a total of 212 patients, Oken and colleagues determined that three to six months of treatment with 120 mg/day to 240 mg/day of Ginkgo biloba produced a "modest effect," which they correlated to a 3% difference in the Alzheimer's Disease Assessment Scale-cognitive subtest (Oken et al., 1998).
A variety of alternative medicine therapies were assessed in the JAMA issue, with some evidencing benefit and others appearing ineffective. A review of the available data on the use of saw palmetto (Serenoa repens) conducted by Timothy Wilt, M.D., and colleagues from the Department of Veterans' Affairs Coordinating Center of the Cochrane Collaborative Review Group in Prostatic Diseases and Urologic Malignancies determined that the herb can improve urologic symptoms in patients with benign prostatic hyperplasia (Wilt et al., 1998).
In the six randomized clinical trials, a chiropractic spinal manipulation was not found effective for episodic tension headache (Bove and Nilsson, 1998). The practice of moxibustion, in which an acupuncture point is stimulated by the heat of burning a specific herb, was deemed helpful in correction of breech presentation in late pregnancy (Cardini and Weixin, 1998). A Chinese traditional medicine mixture of 20 different herbs was found to improve symptoms of irritable bowel syndrome (Bensoussan et al., 1998).
Neither acupuncture nor amitriptyline (Elavil) was ranked superior to placebo in a comparative trial on relieving the pain from HIV-related peripheral neuropathy (Shlay et al., 1998). An herbal ingredient in products marketed for obesity, Garcinia cambogia (hydroxycitric acid), did not prove efficacious for weight loss (Heymsfield et al., 1998). In a preliminary study, a yoga-based intervention did appear useful for relieving some symptoms of carpal tunnel syndrome (Garfinkel et al., 1998).
Although randomized, controlled trials represent the "gold standard" for clinical research, Arthur Margolin, Ph.D., Yale University School of Medicine Substance Abuse Center, and colleagues explained in the JAMA commentary (1998) that there are numerous difficulties in subjecting many alternative medicine treatments to these testing conditions. When an alternative medicine treatment is appropriately administered within a cultural tradition, for example, it is less likely to lend itself to a quantitative, biomedical framework. When control conditions are not as credible as active treatment, blinded testing is less feasible.
Margolin et al. also suggested that controlled evaluation of alternative medicine therapies will require its practitioners to revise their perspective on patients and treatment, and "to undertake a fundamental conceptual shift from a view of patients as requiring individualized treatment that may vary at each session to one in which trial participants are regarded as members of an equivalence class, defined by the diagnosis, who all will be given a standard prescribed treatment."
Despite the difficulties in applying rigorous scientific evaluations to alternative medicine treatments, Lundberg and Fontanarosa insist that these treatments should be so proven before they are accepted and applied. They call for additional research funding for alternative medicine, with emphasis on establishing safety and efficacy; as well as the effectiveness of treatment strategies, with consideration of community practice settings, patient expectations and compliance, and cost-effectiveness.
"However, until solid evidence is available that demonstrates the safety, efficacy and effectiveness of specific alternative medicine interventions," the JAMA editors concluded, "uncritical acceptance of untested and unproven alternative medicine therapies must stop. Alternative therapies that have been shown to be of no benefit...or that cause harm should be abandoned immediately."
Angell M, Kassirier JP (1998), Alternative medicine-the risks of untested and unregulated remedies. N Engl J Med 339(12):839-841. Editorial.
Bensoussan A, Talley NJ, Hing M et al. (1998), Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial. JAMA 280(18):1585-1589.
Bove G, Nilsson N (1998), Spinal manipulation in the treatment of episodic tension-type headache: a randomized controlled trial. JAMA 280(18):1576-1579.
Cardini F, Weixin H (1998), Moxibustion for correction of breech presentation: a randomized controlled trial. JAMA 280(18):1580-1584.
Eisenberg DM, Davis RB, Ettner SL et al. (1998), Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 280(18):1569-1575.
Ernst E, Rand JI, Stevinson C (1998), Complementary therapies for depression: an overview. Arch Gen Psychiatry 55(11):1026-1032.
Ezzo J, Berman BM, Vickers AJ, Linde K (1998), Complementary medicine and the Cochrane Collaboration. JAMA 280(18):1628-1630.
Fontanarosa PB, Lundberg GD (1998), Alternative medicine meets science. JAMA 280(18):1618-1619. Editorial.
Garfinkel MS, Singhal A, Katz WA et al. (1998), Yoga-based intervention for carpal tunnel syndrome: a randomized controlled trial. JAMA 280(18):1601-1603.
Heymsfield SB, Allison DB, Vasselli JR et al. (1998), Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA 280(18):1596-1600.
Jonas WB (1998), Alternative medicine-learning from the past, examining the present, advancing to the future. JAMA 280(18):1616-1617. Editorial.
Margolin A, Avants SK, Kleber HD (1998), Investigating alternative medicine therapies in randomized controlled trials. JAMA 280(18):1626-1628.
Mitka M (1998), FDA never promised an herb garden-but sellers and buyers eager to see one grow. JAMA 280(18):1554-1556.
Oken BS, Storzbach DM, Kaye JA (1998), The efficacy of Ginkgo biloba on cognitive function in Alzheimer's disease. Arch Neurology 55(11):1409-1415.
Shlay JC, Chaloner K, Max MB et al. (1998), Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. JAMA 280(18):1590-1595.
Wilt TJ, Ishani A, Stark G et al. (1998), Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 280(18):1604-1609.