Use of Herbal Medications in Elderly Patients
Author Affiliations: Dr. Scholz is at Vanderbilt University School of Medicine, Department of Medicine, Nashville, TN; Dr. Holmes is at The University of Texas M. D. Anderson Cancer Center, Division of Internal Medicine, Department of General Internal Medicine, Ambulatory Treatment, and Emergency Care, Houston, TX; and Dr. Marcus is at Baylor College of Medicine, Department of Medicine, Section of Immunology, Allergy, and Rheumatology, Houston. ________________________________
Introduction As cultural views of conventional medicine change and patients seek “natural” solutions to health problems, Americans have increasingly turned to herbal medicines.1,2 Herbal medicine use is prevalent in the United States, with 12% of adults in the United States reporting use of herbals, and only about one-third of patients informing their medical doctors about herbal use.1,3 Although only 8% of Americans over the age of 65 use herbal medications, 49% do not disclose this use to their physicians.4 About half of patients believe physicians have a “hostile attitude” about alternative therapies,5 and others may not recognize that herbals are pharmaceutical agents that may cause serious adverse effects. According to the American Society of Health-System Pharmacists, “the widespread, indiscriminate use of dietary supplements presents substantial risks to public health.”6 A growing body of medical literature has documented adverse drug events and lack of efficacy of herbal medications, but regulatory changes have not been forthcoming to help protect patients and to enable clinicians to address herbal medicine use in daily clinical practice. There are no evidence-based guidelines developed by expert panels regarding the use of herbal medicines that are comparable to other guidelines for disease treatment. No clear guidelines exist regarding the use of herbal medicines in the elderly. Herbal medicines have not appeared on any explicit lists of medications to avoid, nor have there been any consensus statements by nationally recognized authorities in geriatric medicine regarding herbal medicine use. Given the potential vulnerability of the older population to herbal medicines, this is a significant gap in guidelines for better practice.7 The purpose of this article is to summarize current data regarding the regulation, efficacy, and safety of herbals, and to suggest how older patients should be counseled about the use of herbal medicines. What Are Herbals, and How Are They Regulated? Herbal medicines are “crude drugs of vegetable origin”8 that are used throughout the world, and in Europe some are prescription medicines.9 However, they were designated as dietary supplements, neither food nor drugs, by the 1994 Drug Safety and Health Education Act (DSHEA).10 DSHEA essentially tied the hands of the Food and Drug Administration (FDA) in regulating these products. There is no oversight of the contents, efficacy, or safety of herbal medicines.11 In vitro or animal studies are not required prior to human trials because of the belief that traditional use implies efficacy and proof of safety.12,13 Because manufacturers can place products on the market without FDA approval, there is no incentive for them to conduct randomized controlled trials.13 Although DSHEA did not require manufacturers to report serious adverse events to the FDA, an amendment now requires reporting to the agency.14 Herbals are marketed directly to consumers. Herbal manufacturers may not make claims to diagnose, treat, prevent, or cure a disease unless these claims are evaluated and approved by the FDA.15 Manufacturers’ claims are often misleading and difficult for the consumer to evaluate.13 Despite these regulations, illegal statements regarding the efficacy of herbals for treatment and diagnosis, and without a mandatory disclaimer that the health claims have not been approved by the FDA, are prevalent on Internet sites, a frequent source of information on herbals for consumers. The majority of websites regarding herbals are retail or vendor sites, and more than half make illegal claims to treat, prevent, diagnose, or cure a specific disease.16 Thus, most of the information available to patients regarding herbal medications comes from vendors rather than a professional or research organization.13 How Do Herbals Differ From Conventional Medications? While touted as safe because they are natural, herbal products are medications. The body does not distinguish between chemicals in a crude extract of a plant and a purified drug. Proponents of herbals say that supplements intended merely to “improve or sustain the structure or function of the body” should not be regulated, in contrast to drugs, which “prevent, treat, or cure a disease.”12 However, after the passage of DSHEA, intention to treat a medical problem was among the most common reasons for which consumers reported use of herbals.5 Although herbals are advertised as “standardized,” they are not standardized for biological activity, and analysis of popular herbals demonstrates that their contents are variable and not consistent with their labeling.17 Moreover, because of DSHEA, listing of ingredients is not required.15 Herbals may also be adulterated with contaminants and prescription medications, such as heavy metals in valerian or caffeine in yohimbine. Colchicine has been identified in Echinacea and Ginkgo biloba. However, some contamination has been with prescription or over-the-counter (OTC) medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), ephedrine-like compounds, and relatives of sildenafil. Not only does this violate the Federal Food, Drug, and Cosmetic Act of 1994, but these contaminant drugs have their own side-effect profiles and drug interactions. Thus, even when patients report herbal product use to physicians, it is not always possible to know what the patient is actually consuming.18 Efficacy and Safety of Herbals There is no definitive evidence for efficacy of individual herbal medicines. Many trials that demonstrate the efficacy of herbals have methodological flaws, including inadequate randomization, inadequate blinding, lack of intention-to-treat analysis, and small sample sizes.19-21 Studies of herbal medicines that are funded by the herbal industry are more likely to report positive results, as is the case with glucosamine for osteoarthritis.19 Rigorous randomized controlled trials funded by independent sources have shown no efficacy for Echinacea, saw palmetto, and black cohosh.22-24 Characteristics of the most commonly used herbal medicines are summarized in the Table.22-38 The belief that herbals are efficacious and safe is based on their long history of use, unfounded belief in “natural” medicines, and the lack of systematic study.5,9 There are virtually no trials of herbal medicines that include monitoring of hepatic or renal function. Unlike herbal medicines, the safety of medications that require FDA approval is studied in clinical trials in thousands of patients, and uncommon serious adverse events may be noted only during post-marketing surveillance.13 As herbals are not required to pass preliminary safety studies, adverse events may not be noted until many patients have used the product over many years. Most serious adverse events caused by herbals have been reported to Poison Control Centers rather than to the FDA.39 Rates of adverse event reporting for herbal products are also disproportionately low, because consumers and some physicians believe that herbals are harmless. The Office of the Inspector General of Health and Human Services concluded that the current practices for adverse event reporting for herbal supplements are “inherently limited” and that the FDA “rarely takes safety actions related to the adverse event reporting system.”39 Even when reports are made, insufficient case data may be available to fully investigate the claim, and formal prospective pharmacoepidemiology studies are necessary to establish causality.13 Large numbers of patients must use a drug before all associated adverse events may be noted. NSAIDs are in exceedingly common use, but the prevalence of associated risks of serious gastrointestinal bleeding and myocardial infarction were only noticed after a decade of post-marketing surveillance.40 Most herbal medications are less frequently used than NSAIDs, so even ten years of surveillance may be inadequate to observe serious adverse events.40 For example, if a particular adverse event occurs in one of a thousand patients taking a particular medication, a single physician would need to treat 4800 patients with that medication to have a 95% chance of seeing that particular adverse event more than once. For that to occur would require placing a new patient on the medication every working day for 18 years.41 Herbal Medications in the Elderly The impact of herbal medications in the elderly is an important but ill-defined issue.42 The contribution of herbal medicines to adverse drug reactions (ADRs), hospitalization, and nonadherence to conventional medications is unknown.43,44 Despite less common herbal use in the elderly, appreciable numbers of older patients take herbal medicines.4,45 Two-thirds of people over age 65 years who take herbal medicines also take at least one prescription medication.4,44 Older patients may be more inclined to view herbal medicines as an alternative to avoid overuse or excess cost of prescription medications.44 Older persons may be more vulnerable to drug interactions and toxicities of herbal medicines due to polypharmacy and age-related changes in pharmacokinetics. However, the contribution of herbal medicines to this risk is unknown in the elderly. Not only is there a lack of information about the impact of aging on commonly used medications, but there is also a substantial knowledge gap about the pharmacokinetics of herbal agents themselves. Examples of Specific Problems with Herbals in the Elderly About 20% of older people with arthritis take herbals, and nearly half of older persons with arthritis take NSAIDs.46 Concern over the limitations and adverse effects of conventional medications for arthritis may lead patients to try herbals such as ginger.47 However, ginger contains cyclooxygenase inhibitors and can cause many of the same adverse effects caused by NSAIDs, without warnings to consumers who have renal insufficiency, heart failure, peptic ulcer disease, or who are taking anticoagulants.48,49 Sexual problems are common in older persons and are infrequently discussed with physicians,50 raising concerns about patients’ self-medication for sexual disorders. Many herbal products are marketed to improve “sexual vigor,” and there have been numerous reports of identification of prescription medications in such products, especially the phosphodiesterase inhibitors sildenafil, tadalafil, and vardenafil.51,52 Such adulteration presents a serious danger to those taking vasodilator medications who may be taking herbal medicines in order to avoid the interactions of prescription phosphodiesterase inhibitors. Given the prevalence of chronic illness in the elderly and the prevalence of prescription medication use, herb-drug interactions are of significant concern in older persons. The most well-described herbal-drug interaction is caused by St. John’s wort. Promoted for treatment of mild depression,39 St. John’s wort induces the cytochrome P-450 3A4 isozyme, lowering blood levels of 50% of commonly used medications, including immunosuppressants, statins, benzodiazepines, calcium channel blockers, HIV medications, chemotherapeutic agents, and many others.38 Weight loss products should be avoided in the elderly. Even those that advertise being “ephedra-free” may contain ephedra-like products or caffeine. The use of these products could result in tachyarrhythmias, myocardial infarction, hypertension, or stroke.11,53 Other products in herbal weight loss medicines are not effective for weight loss, and they commonly cause side effects such as bloating and headache. A systematic review of weight loss therapies concluded that none of the supplements for reducing body weight should be recommended for OTC use.54 Conclusions and Recommendations Herbal medicines have little evidence of efficacy and growing evidence of toxicity despite the absence of effective reporting of adverse events. Herbals should be considered inappropriate medications in the elderly, largely because few data of acceptable quality exist regarding the efficacy and safety of these agents in any population. Because the elderly represent a more vulnerable population, it is important that healthcare providers discuss the benefits and risks of herbal medicine use with older patients. Older patients with multiple chronic conditions may easily be frustrated with their health status; one should admit the shortcomings of conventional medications but also emphasize that the patient is receiving the best known therapy. Since 81% of people believe that the FDA should ensure safety of herbal supplements,5 many patients may not want to pursue herbal options after hearing about the lack of regulations. Patient autonomy must be acknowledged and respected. Patients may not be willing to notify their physicians of herbal use, and physician recommendations on this matter should be informative but not paternalistic. Herbal medicine use should be assessed frequently, and questions should be directed to help disclose the complete use of herbals, dietary supplements, natural remedies, and nonprescription medications.55 If a patient adamantly desires herbal products, one must equip the patient to appropriately judge these therapies. Patients need to know about the uncertainties of product content and activity, expected benefits and side effects, drug interactions, and how to report adverse events should they occur. Information about herbal products from the Internet and from sources likely to gain from the sale of those products should be viewed with a healthy dose of skepticism.16,56 Above all, physicians must strive to educate patients about the nature of herbal supplements. Naturally occurring substances are chemically active compounds. The same elements make up herbs and conventional medications alike, but conventional medications are purified, characterized, and scrutinized for safety and efficacy. The authors report no relevant financial relationships.