Mixed meds

Think twice before mixing your herbs and your prescription medicine.

Published February 17, 2000 5:00PM (EST)

The cafeteria of this psychiatric clinic is especially packed on a rainy February night. But the members of this manic depression support group say attendance always increases when there's a speaker. The guest tonight, a young pharmacist, is here to talk about the illness they all face -- and to advise the 50 or so people on what to do and what not to do when taking so many medications at once.

But every time the pharmacist starts to explain something, she is interrupted mid-sentence by someone yelling out a question: "Can I mix lithium with an anti-inflammatory?" No, she responds politely, and that means Advil, too. "You say I need to drink a lot of water while on my medication. Can I still go to the steam room twice a week?" Yes, just make sure you replenish your lost water. As each inquiry comes in, she answers it with an almost-perfect textbook recitation of some pharmaceutical manual.

That is, until a woman toward the end of the evening asks, "How about the herbs? Is there an interaction with my medication?"

"Not that I know of."

Her response is unfortunately representative of her field. Many pharmacists, physicians and other health-care professionals aren't trained in herbal medicine, and are, therefore, unfamiliar with the dangerous side effects that can arise when such remedies are combined with prescription drugs.

With the growth of the $12 billion alternative-medicine business, and the prescription drugging of America, a $134 billion empire, the two worlds are meeting or, as one leading researcher says, "colliding." With the same glass of water, herbs, dietary supplements and natural products are being washed down with prescription drugs. And as Adriane Fugh-Berman wrote in a recent editorial in the Lancet, "All ingested substances have the ability to interact."

At the clinic, Annette Brown, sitting about 10 rows back, listens intently. It's her first time at this support group. The mother of two later opens her eyes wide with enthusiasm and speaks quickly when explaining what happened to her only a month earlier. Though she was diagnosed years ago with manic depression, she sought treatment for it only recently. Her doctor prescribed the antidepressant Paxil, which she took for several weeks. "I felt anxiety, shaking inside, tightness in my arms and legs; every muscle tensed up; I would try to relax but it still hurt," she says as she points to the afflicted areas. "I just kept thinking, 'Paxil is messing with me.'" Her doctor then switched her medication.

What Brown didn't tell her doctor was that she was also taking another pill to combat her depression: St. John's wort, also known as hypericum perforatum. Though it's hard to say for sure what happened to Brown, the popular herb is believed to interact with certain antidepressants, also known as selective serotonin reuptake inhibitors (SSRIs), such as Paxil, Zoloft and Prozac. The interaction can cause serotonin syndrome, with symptoms that include restlessness, muscle twitches and shivering. "I didn't tell my doctor because I never considered it a drug," she says. "After all, it's an herb; it's natural."

Two new studies in last Thursday's the Lancet provide further evidence that St. John's wort is not quite the harmless little herbal many people believe it is. The new research (which prompted the Food and Drug Administration to issue a health advisory) shows that St. John's wort can interact with the commonly used HIV protease inhibitor indinavir, and cyclosporine, an immunosuppressant drug used to prevent rejection after organ transplants. "The common misconception is that because it's natural, it's safe," says Stephen Piscitelli of the National Institutes of Health, author of the HIV study. Since so many people with AIDS also suffer from depression, and take meds to combat it, Piscitelli and his colleagues kept hearing anecdotes of an interaction and decided to look into it. His concerns seem to be justified: St. John's wort, he found, reduces the blood plasma concentrations of indinavir, which can lead to not only drug resistance but to treatment failure. "This study clearly shows that there can be dangerous interactions when you get St. John's with other drugs," he says.

According to a 1998 study in the Journal of the American Medical Association, 15 million people are using dietary supplements, and 18 percent are taking them in addition to their prescription medicine. As a result, pharmacists report interactions between synthesized medicine and natural products are increasing; research into the causes is not.

"It's not a new problem; it's a problem that's growing in numbers because far more people are combining natural products with drugs," says Forrest Batz, assistant professor in the department of clinical pharmacy at the University of California at San Francisco and associate editor of the "Natural Medicines Comprehensive Database." The database is kind of the bible of herb/drug interactions, and includes clashes, like the one between Lanoxin (digoxin), which is used to treat heart conditions, and St. John's wort. There have also been cases where gingko biloba, when taken with the blood-thinner Coumadin (warfarin) has caused spontaneous bleeding. Grapefruit juice supplements can increase the blood levels of people taking any of the cholesterol-lowering drugs like Mevacor (lovastatin), Zocor (simvastatin) and Lipitor (atorvastatin); and when combining neuroleptic drugs and betel nut there is an increased risk of extrapyramidal side effects like spasms and tremors.

On the flip side, having a dietary supplement interact with a prescriptive might be something we want. Herbalists point to "positive" cocktails, where the supplement's presence either magnifies the effect of the drug in a good way, or reverses a side effect of a medication. Gingko, for example, is believed to reverse the sexual dysfunction many people on antidepressants experience. And supplements containing lacto bacillus acidophilus may reduce or prevent antibiotic-induced diarrhea.

"While we have to be cautious about it, we shouldn't be afraid of it," says Roy Upton, executive director of American Herbal Pharmacopoeia. "Also, when you look at the data worldwide, it's not a big problem. Most of the information is either theorized or based on animal studies."

And that is the problem. There is no medical literature. Herbalists will point to this to downplay the situation. Pharmacists, who are often at odds with them, will say there are no papers because there's been no research money funneled into this field. No research means no literature.

"It's resource-intensive to look at herb/drug interactions but in the U.S. with the amount of resources (we have), we are capable of doing that," says Richard Ko, a food and drug scientist responsible for regulating ethnic drugs, like Chinese herbs, for the California Department of Health Services. "Right now, the companies are under no obligation and have no incentive to do the research, especially the herbal manufacturers. That's why most of the research on herbal products is mainly being done in Japan and European countries."

And that brings up the larger issue of how dietary supplements are regulated in the United States. Many countries consider them drugs, and manufacturers fund the studies required before a new remedy can be sold. In the United States, the Food and Drug Administration regulates dietary supplements less stringently than it does drugs and food. As a result, the makers of these products are not required to report adverse reactions even when they learn about them. So there isn't an agency thoroughly tracking these kinds of interactions. A spokesman for the American Association of Poison Control Centers says they have noticed an increase in calls but, at best, the evidence is anecdotal.

Although some companies do voluntarily provide information, this regulatory fact greatly reduces the number of adverse reactions and side effects reported to the FDA; most of the information it receives comes from consumers and doctors and is reported to the FDA's MedWatch program. An official at the FDA says that if the Center for Drug Evaluation and Research had to rely only on the MedWatch program -- which accounts for only 6 to 10 percent of all the drug-to-drug interactions being reported -- it would be receiving only a trickle of the information it receives now.

Indeed, what the FDA receives on dietary supplements is a trickle. Since 1993, when the Center for Food Safety and Applied Nutrition started looking at adverse reactions to dietary supplements, it has recorded 2,621, and 101 people have died as a result. But these numbers don't tell us whether the reactions are to a dietary supplement, or to an herb/drug interaction. Also, these statistics are from 1998 -- the last time the center made the numbers public. (The FDA asked Congress for an additional $2.5 million to monitor supplements but the money was denied.)

"They get fewer reports than we do," says Dr. Peter Honig, deputy director of the FDA's office of post-marketing drug risk assessment. "It's just the nature of voluntary reporting; the consumers are not necessarily tuned in to the reporting of dietary supplements, nor are physicians." Honig says in order to receive more reports on dietary supplements, either a law would have to be written to require reporting from its manufacturers, or consumers and physicians would have to overcome the barriers that prevent them from reporting interactions.

Pharmacists say one of the main reasons why reporting is scarce is that many doctors don't recognize herb/drug interactions when they see them. A patient may report an interaction but the doctor might think it's just the prescription medicine that's causing the adverse effects.

Georgetown University researcher Dr. Raymond Woosley suspects that many adverse reactions attributed to prescription drugs may actually be caused by an interaction between a dietary supplement and the drug. He points to a report last year on medical errors that cited adverse drug reactions as one of the leading causes of medically related deaths in the United States.

"It's very possible that a large fraction of that could be caused by drugs used with herbs. We don't have the data but recent papers show that it can react," says Woosley, Georgetown's pharmacology department chairman. "People say they're natural, but so is snake venom."

While the dietary supplement industry will hardly say that everything under the umbrella of "dietary supplements" or "natural medicine" is safe, they do contend that these substances are less potent, overall, than Western medicines. In many cases, they are also less expensive. "I'm not going to deny that there's a perception that natural is, as a rule, less dangerous than a pharmaceutical substance," says Michael McGuffin, president of the Herbal Products Association, a trade association representing manufacturers and marketers of dietary supplements. "I'm also not going to deny that in fact, natural botanicals are as a rule less dangerous than pharmaceutical substances. (Although) you need to find the references to know which botanicals to use during different stages of life, like pregnancy."

Whether they turn to these reference sources or not, people are turning to alternative medicine. Their reasons include everything from a distrust of the medical establishment to almost a spiritual belief in these products to a feeling of individual responsibility for their health. What they haven't always included in the regimen is communication about their self-medication. It's not that people are locking themselves in dark rooms, popping their pills and not telling anyone about it. More often, as with Annette Brown, they believe their herbs are harmless and, therefore, not worth mentioning to a doctor. A recent study looking at breast-cancer patients, presented last month at UCSF's International Congress on Women's Health Issues, found that 72 percent used some form of alternative treatment in conjunction with their usual treatment. And only one-third told their doctors about it.

"Sometimes when patients aren't talking about something, people may read into it that they are being secretive," says Shelley Adler, professor of medical anthropology at UCSF. "But it's more complicated than that; there's a logical and rational strategy that patients use." And those reasons, she found, varied. Many thought that their doctors just weren't interested; others thought that their alternative medicine was not relevant to their other treatment. And some thought it was almost a moot point because even if they told their physician, he/she wouldn't be able to give them any useful information.

"When I said to my oncologist, 'I've used shark cartilage,' he almost laughed me out of the office," said one patient.

"I did tell the doctor and he didn't say, 'Good,' or 'Not good,' or 'OK' or anything," said another.

That is what happened to Katie Allen, a sickle cell research nurse living in Oakland, Calif., when she told her physician about all the Chinese herbs, vitamins and antioxidants she was taking to fight her breast cancer. He just shrugged. So just before starting chemotherapy, she went to see a consultant, brought up the different treatments she was on and asked for his opinion. "He said if the antioxidants protect all these healthy tissues (from the chemotherapy), it might also protect the cancerous cells from the Adriamycin (doxorubicin)," she says. "I had to make a choice, and something had struck me about what he said."

Indeed, the dietary supplement industry's McGuffin believes that physicians have to create an environment that is more respectful of patients' treatment choices. "The message to health-care providers is to respectfully receive the information. Stop telling them that they are dumb for believing that vitamin C and echinacea is good for them."

According to Adler's study, patients were more likely to tell their doctors about their alternative medicine use when their physicians expected them to be on supplemental treatment. If a doctor broaches the topic with sensitivity, the patient will be more likely to respond. A sample question for a doctor, she says, might be: "People use a variety of different methods to maintain or improve their health. What kind of things are you doing to take care of (your health/this problem)."

Susan Winckler, group director of policy and advocacy at the American Pharmaceutical Association, says that a blending of the pharmaceutical and herbal worlds will require improved communication between patients and their doctors and pharmacists. "You can't disconnect the health care from the self care," she says. "There needs to be some type of bridge connecting the two."

And that bridge, many critics say, has to happen in doctors' offices, and at the pharmacy counters. While Winckler says it's happening on a smaller level at pharmacies across the country, the most public step by the health-care industry came last month when CVS, the second-largest pharmacy chain in the United States, announced that it is tackling this problem. When customers come in, a form will be given to them, asking them not only what other medicines they're on, but also what dietary supplements they're taking. This information will then be entered into the computer -- as prescription drugs already are -- and the substances will be cross-checked for possible interactions. "Our pharmacists were getting more and more questions from our customers about the safety of these products," says Mike De Angelis, spokesman for CVS. "The service we're offering now is an extension of technology we've always had in the pharmacy to cross-check for harmful interactions."

People on all sides of the issue applaud CVS' initiative and believe it will be commonplace in the years to come. A spokeswoman for Walgreens says the company is looking into implementing a similar system. But pharmacists also acknowledge what CVS and other companies are up against, since so little is known about the interactions. For example, how plausible will it be to check prescription medicine against a natural product when the components of that product aren't known, or may be prepared differently or mixed with some other type of natural herb?

"As a pharmacologist, I would never argue that those plants don't have value, but the product that we put in these pills is more pure and a better characterized product than the plants," says Woosley. "There are too many variables -- how long they're harvested, how well they were ground up, whatever is mixed in with it. People have died from teas that they have drunk that have wiped out their liver. That's why more research needs to be done."

That's one point all sides agree on.

By Dawn MacKeen

Dawn MacKeen is a former senior writer for Salon, and author of a forthcoming book about her grandfather’s survival of the Armenian Genocide, "The Hundred-Year Walk: An Armenian Odyssey" (Houghton Mifflin Harcourt, January 2016).

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