US Pharm. 2012;37(11):12-15.
Patients ask pharmacists profound questions about nonprescription products. Many queries center on the products’ potential to cure serious medical conditions that should only be treated by a physician. In these instances, it is the duty of the pharmacist to stress the necessity for seeking physician care. This is an especially acute situation when the patient’s request involves certain OTC products such as dietary supplements (other than vitamins and minerals), herbs, homeopathics, and some medical devices (e.g., ear candles).1
St. John’s Wort
St. John’s wort (SJW or Hypericum perforatum) is a good example of a problematic herbal product. It has been used for centuries, especially in Europe. Its popularity rose in the United States in the 1990s due to its purported antidepressant action. It has been proposed that the chemicals hypericin and hyperforin in SJW may help regulate mood.2
Available by Prescription in Other Countries
Some countries take great care with SJW, spurred by concerns about its safety. France totally banned its sale, based on a report issued by the French Health Product Safety Agency that expressed concern about significant drug interactions.2 Ireland banned it from nonprescrip-tion sale in January 2000.3 This decision was made by the Irish Minister for Health based on the findings of the Irish Medicines Board. The board was concerned about such adverse effects of SJW as fatigue and photosensitivity, as well as its potential to cause dangerous interactions. When the decision was made, it was estimated that 75,000 Irish citizens were SJW users, and the outcry from users and health shop owners was angry and immediate. At first, the new law did not cover importation, allowing users to import the herb for personal use. Later, this loophole was closed, and SJW was banned from mail order and Internet sales. Further, residents of Ireland could neither phone nor fax an order to another country to be filled and mailed back to them.
Germany’s regulatory agency for herbs is known as Commission E. In a manner similar to Ireland’s action, the commission restricted SJW to prescription-only status.4 Some countries that allow nonprescription SJW sales are rethinking the ramifications of that policy on public safety. Japan, the United Kingdom, and Canada are all in the process of requiring drug-herb warnings on SJW packaging.2
OTC in the U.S.
U.S. citizens do not have the same protection from unproven nonprescription products as those in Germany and Ireland. In fact, the general definition of “fraud” does not seem to apply to unproven products. The FDA, for purposes of criminal investigations, defines health fraud as: “The deceptive promotion, advertisement, distribution or sale of articles, intended for human use or animal use, that are represented as being effective to diagnose, prevent, cure, treat, or mitigate disease (or other conditions), or provide a beneficial effect on health, but which have not been scientifically proven safe and effective for such purposes.”5 Thus, it would seem that SJW meets the definition of fraud if therapeutic claims are made for it. So how can it be sold in the U.S. without the vendors being guilty of fraud?
This unfortunate situation is largely due to the work of U.S. Senator Orrin Hatch of Utah.6,7 Utah has long been known as a major center of unproven dietary supplement manufacturing and marketing, being derisively referred to as “cellulose valley.”8 Senator Hatch championed a law known as the Dietary Supplement Health and Education Act (DSHEA) to enhance and expand the sale of OTC products. The 1994 law created a new class of nonprescription products, to be known as dietary supplements. According to this law, those wishing to market these products do not need to prove their safety and efficacy prior to sale, nor are they required to establish a safe and effective dosage.9 The DSHEA restricts the FDA from acting against unproven products until they have already injured and/or killed American citizens.10 Unproven homeopathic sales are allowed under an older loophole in federal law.11
After Congress passed the DSHEA and it was signed into law by President Bill Clinton, the U.S. regressed medically to the time before 1906, when dangerous and ineffective patent medicines killed or permanently ruined the health of an unknown number of Americans.7 In regard to dietary supplements, the U.S. post-DSHEA is little different from countries whose predominant medical systems are ungrounded in evidence-based medicine.12
It is also critical to note that marketers of dietary supplements and herbals are allowed to omit vitally important information from their labels. Labels seldom (if ever) include information regarding adverse reactions that can be expected, what to do if an adverse reaction occurs, dangerous drug interactions, when to seek the care of a physician, whether the supplement is safe in pregnant or nursing women, ages below which the product should not be taken, or the maximum duration of use before the patient should seek physician care. The sponsors of the DSHEA ensured that no government agency has the power to force supplement marketers to issue appropriate warnings to the public about their products prior to purchase, and instead the FDA must wait until after products have already caused patient harm.9,10
This is the short answer to the pending question regarding fraud in the sales of unproven dietary supplements such as SJW: A specific law was passed that legalized sales of products that, according to the FDA definition, meet the criteria for fraudulent. DSHEA does require unproven supplements to carry a warning label informing patients that any claim made (e.g., “supporting health” or reducing the risk of developing health problems) is not proven. The warning reads: “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.”10
Reliable Information on St. John’s Wort
The Internet is a mass of random information that consumers can access without restriction. When one attempts to research SJW, Google returns 1,330,000 potential pages. Many are full of blatant misinformation, being sponsored by marketers and other individuals who lack medical training. Pharmacists can point out credible resources such as the MedlinePlus monographs sponsored by the U.S. National Library of Medicine (NLM) and the National Institutes of Health (NIH).2 Another reliable source is the set of monographs published by the National Center for Complementary and Alternative Medicine (NCCAM).9
Efficacy of St. John’s Wort
Study results on the effectiveness of St. John’s wort for depression have been mixed. NCCAM characterizes research on SJW efficacy as “inconsistent,” highlighting a study by the NIH/NCCAM that found it no more effective than placebo in treating major depression of moderate severity.9 To be fair, NCCAM also observed that sertraline fared no better. The difference is that sertraline was FDA approved for legitimate medical use in the U.S. through a New Drug Application that thoroughly examined its safety and efficacy, with dosing established through scientific studies, information that is lacking for SJW. NCCAM also mentioned that existing studies demonstrate that SJW may benefit patients with minor depression, similar to the way standard antidepressants do.9
The remaining issue is whether these questionable benefits are outweighed by the potential dangers of medically unsupervised use. The NIH examined a set of guidelines promulgated by the American College of Physicians/American Society of Internal Medicine, and issued this statement: “Since St. John’s wort does not appear to be more effective or significantly better tolerated than antidepressant medications, and since St. John’s wort causes many drug interactions, the guidelines suggest it might not be an appropriate choice for many people, particularly those who take other medications.”2
Safety of St. John’s Wort
Fortunately, SJW and the majority of other herbs are fairly safe for most people. However, it is critical to warn potential purchasers of possible adverse reactions. SJW can cause trouble sleeping, vivid dreams, restlessness, anxiety, irritability, stomach upset, fatigue, dry mouth, dizziness, headache, skin rash, diarrhea, and tingling.2 Its safety in human pregnancy is unknown, but it may have been responsible for birth defects in rats, so its use should be avoided in pregnancy. Breastfed infants can experience colic, drowsiness, and listlessness if the mother takes it, and it should therefore be avoided when breastfeeding. It may interfere with conception, and should be avoided by those who wish to become pregnant. It has been implicated in worsening symptoms of attention-deficit/hyperactivity disorder (ADHD), causing mania in patients with preexisting bipolar disorder and major depression, causing psychosis in patients with schizophrenia, contributing to dementia in those with Alzheimer’s disease, and causing heart problems during surgery requiring anesthesia.2
SJW has the potential for many drug interactions, with at least one (an interaction with cyclosporine) having caused a patient death.1 It interacts with alprazolam, amitrip-tyline, carisoprodol, citalopram, clopidogrel, dextromethorphan, diazepam, digoxin, fexofenadine, itraconazole, HIV/AIDS medications, ketoconazole, lansoprazole, lovastatin, narcotics, nortriptyline, omeprazole, oral contraceptives, phenobarbital, phenytoin, sertraline, tramadol, triazolam, warfarin, and many others.2
SJW also increases the risk of photosensitivity and is especially dangerous when taken with other photosensitizers. This list includes amitriptyline, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, tetracycline, and trimethoprim-sulfamethoxazole (TMP-SMZ).2
A Return to Rationality?
To remedy the untenable situation described above would require a champion in Congress who would battle for a law to protect American citizens from products of unknown safety and efficacy. (Note that the Dietary Supplement Safety Act of 2010 was withdrawn.13) The ideal law would completely repeal the DSHEA. It would immediately force all unproven nonprescription products and devices from the market, with vigorous prosecution of those who would persist in marketing or selling them in any location. It would also require all marketers of herbals, dietary supplements, homeopathics, and medical devices to submit proof of safety and efficacy to a newly empowered FDA before their reintroduction to the market. It would allow the FDA to immediately recall any product that caused patient harm. The American public deserves no less.
Should You Use St. John’s Wort for Depression?
Dietary supplements are sold in thousands of locations throughout the United States, including grocery stores, pharmacies, and health food stores. Because these OTC products are not FDA approved, their safety and effectiveness are unknown. By law, supplement labels must include the following disclaimer: “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.” For this reason, purchasers are gambling with their health whenever they ingest herbal supplements such as St. John’s wort to treat symptoms of depression.
Treatment of Depression
Depression is a difficult medical condition to treat. First of all, it should not be self-diagnosed. Depression should only be diagnosed by a physician, according to criteria that trained health care professionals can fully utilize. Second, if treatment is necessary, patients are best advised not to treat themselves with herbs of unknown efficacy. Prescribed medications are known to be effective. Antidepressants do have risks to their use (side effects may include nausea, insomnia, weight gain, and decreased sex drive), but the role of the physician is to balance these risks against the benefit of proven effectiveness in treating depression.
Risks of St. John’s Wort
Because full scientific scrutiny has not been conducted on St. John’s wort, it is risky to use. The first risk is one that could occur if the herbal supplement actually worked as advertised. Physicians are aware that depressed patients are often physically unable to take the steps they might otherwise take to deal with their life circumstances. If the depression is treated successfully, patients emerging from the cloud of depression may actually find the energy to cope with their lives by committing suicide. Physicians can warn patients and their caregivers to watch carefully for signs of impending suicide. If patients purchase St. John’s wort in a health food store, for example, there is no one who can professionally advise them about this potential.
Other risks arise from the fact that St. John’s wort contains potentially dangerous chemicals. The herb can cause skin sensitivity and damage when one is exposed to sunlight while using it, which is known as photosensitivity.
Drug interactions are also a major concern. St. John’s wort can potentially interact with hundreds of prescription drugs, including antibiotics, other antidepressants, immunosuppressive agents such as cyclosporine, HIV medications, oral contraceptives, and warfarin.
Whether dietary supplements like St. John’s wort can do any good for you is an open question, as their ability to help any medical condition is not established. There may be risks to their use, but marketers are not required to put any such warnings on product labels. This is not a healthy situation for America’s consumers. If you plan to take St. John’s wort, at the very least read about the product thoroughly beforehand so you can be fully aware of its risks and benefits. It is also a good idea to discuss any OTC supplements you might be taking with your health care provider.
Remember, if you have questions, Consult Your Pharmacist.
1. Pray WS. Nonprescription Product Therapeutics. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.
2. St. John’s wort. MedlinePlus. www.nlm.nih.gov/medlineplus/druginfo/natural/329.html. Accessed September 25, 2012.
3. St. John’s wort to remain prescription only. Irishhealth.com. www.irishhealth.com/article.html?id=384. Accessed September 25, 2012.
4. St. John’s wort. American Cancer Society. www.cancer.org/Treatment/TreatmentsandSideEffects/ComplementaryandAlternativeMedicine/HerbsVitaminsandMinerals/st-johns-wort. Accessed September 25, 2012.
5. CPG Sec. 120.500 Health Fraud—factors in considering regulatory action. Inspections, compliance, enforcement, and criminal investigations. FDA. www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm073838.htm. Accessed September 25, 2012.
6. Pray WS. Orrin Hatch and the Dietary Supplement Health and Education Act: Pandora’s box revisited. J Child Neurology. 2012;27:561-563.
7. Pray WS. A History of Nonprescription Product Regulation. New York, NY: The Haworth Press, Inc; 2003.
8. Ressner J. Industries: state of relief. Time. October 1, 2006. www.time.com/time/magazine/article/0,9171,1541294,00.html. Accessed September 25, 2012.
9. St. John’s wort and depression. National Center for Complementary and Alternative Medicine. http://nccam.nih.gov/health/stjohnswort/sjw-and-depression.htm. Accessed September 25, 2012.
10. Office of Dietary Supplements. Frequently asked questions (FAQ). http://ods.od.nih.gov/Health_Information/ODS_Frequently_Asked_Questions.aspx. Accessed September 25, 2012.
11. Miller HI, Longtin D. Death by dietary supplement. Forbes. March 23, 2010. www.forbes.com/2010/03/23/dietary-supplemetns-herbal-fda-opinions-contributors-henry-i-miller-david-longtin.html. Accessed September 25, 2012.
12. Pray WS. Health fraud and the resurgence of quackery in the United States: a warning to the European Union. Pharm Policy Law (Amsterdam). 2009;11:113-152.
13. McCord D. The Dietary Supplement Safety Act: support for proposed legislation is quietly withdrawn. Sedgwick Law. March 2010. www.sdma.com/publications. Accessed September 25, 2012.
14. “Hammer8.” Prescribed citalopram but taking St Johns (sic) wort. NetDoctor.co.UK. www.netdoctor.co.uk/interactive/discussion/Prescribed-Citalopram-but-taking-St-Johns-Wort-t50797-f3.html. Accessed September 25, 2012.
To comment on this article, contact email@example.com.