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St. Johnís Wort: Too Good To Be True?
In our culture we seem to have the idea that if we pop the right pill, our dissatisfaction or discomfort will be assuaged. Lately, herbal drugs have become very popular as alternative medicines. They are purported to heal everything from memory problems to sexual dysfunction. One of the most common and most controversial herbal remedies is St. Johnís Wort. As a cheap over-the-counter antidepressant, and with over 17% of the population experiencing depression sometime in their lifetime, its allure to the lay person is not surprising (Kessler, R. C. et al., 1994). Is St. Johnís Wort an effective treatment for depression as many claim it is? Is it really safe?
St. Johnís Wort, often called hypercium for its botanical name, Hypercium perforatum, is derived from a yellow flowering plant. Hypercium is native to Europe, western Asia, North Africa, Madeira and the Azores, and has been transported to and grows wild in parts of Australia and North America (Cracchiolo, 1999). Extracts of the plant have been used in European folk medicine for centuries (Kim, 1999), and in Germany today, Hypercium is used above all other antidepressants (Volz, 1997). Hypercium can be taken through infusion, powder, tincture, fluid extract, or oil, and because there is no standardization, doses range from 0.4mg to 2.7mg, and 300-1000mg of crude extract per day (www.frontiercoop.com/herbfest/98/notes/snjwort.html ).
Advertisements and Other Web Sites About St. Johnís Wort
Hypercium has become popular in the United States because of its scientifically documented antidepressant properties with much of the evidence coming from European countries . Because the FDA has not approved Hypercium for any medical purpose, there are many varying reports of its effectiveness (Cracchiolo, 1999). The said effectiveness often seems to be correlated with the purposes of the reporting organization, and therefore, any information about hypercium should be regarded with caution.
The most dramatic reports of the efficacy of the herb come from commercial organizations that are trying to make a profit. Vital Source, www.intellex.com/~gilbert/johnwort.html, claims that Hypercium is the most thoroughly researched natural antidepressant available. While Hypercium may in fact be the most thoroughly researched natural antidepressant, one must consider the number of other natural antidepressants there are. There are very few, if any, and this advertisement seems to suggest to the reader that because there has been so much research, it is a safe drug to take. The advertisement goes on to say that Hypercium relieves anxiety, apathy, sleep disturbances, insomnia, anorexia, and feelings of worthlessness with no dangerous or long term side affects. Joy of Herbs, www.joyofherbs.com/stjohnswort/, claims that Hypercium balances the nervous system which helps to elevate mood. This claim brings to memory Hippocratesí assumption that psychological disorders occurred when one of the four humors were out of balance. LST Services, www.synpds.com/wort.htm, claims that Hypercium assists in and modulates the mindís perception of happiness. The advertisement also states that the herb has been shown to be safe and effective in 21 well controlled human clinical studies. There is no mention of the number of negative studies, and therefore the number of negative versus positive finding may be out of proportion. Again, the consumer is being misled. Healthy Body, www.healthybody.org/st_johns.htm, claims that Hypercium outperformed tricyclic antidepressants such as imipramine and maprotoline. Lichtwer Pharma United States Incorporated, www.lichtwer.com/kira/what/_kira.html, claims that Hypercium has no sedative effects, does not interact with alcohol or caffeine, and has no known interactions with prescription drugs. This claim seems antithetical to the Vital Source advertisement in that Hypercium has no sedative effects. The Vital Source advertisement states that Hypercium relieves insomnia. The Herbal Information Center, www.kcweb.com/herb/store_al.htm, claims that Hypercium may be effective for insomnia as well. Can it do both at the same time? The Herbal Information Center also claims that the active ingredient in St. Johnís Wort, hypercin, contains flavonoids and xanthones which are MAO inhibitors. Depressive symptoms are therefore ameliorated by the MAO inhibitors in the herb. There is no mention of the special diet that a patient must be on when taking MAOIs because of possible adverse reactions, and therefore, this ad is dangerous.
Commercial advertisements make dramatic claims to sell their product. The information they provide is often contradictory and dangerous, with little or no scientific evidence. Though many of the sites have disclaimers on the bottom of the page which say that the products are not intended to diagnose, cure, treat, or prevent any disease, most people choose to ignore the small font, and go buy the drug because of the earlier claims.
Advertisements by organizations whose purpose is to disseminate information about herbs, and sites that serve the purpose of providing the public with scientific medical news have more reliable information. On an Herb Fest Seminar site, www.frontiercoop.com/herbfest/98/notes/snjwort.html, Roy Upton gives a brief, but fairly comprehensive synopsis of the research on St. Johnís Wort today. He talks about current research and its shortcomings, gives dosage advice, mentions that there is no standardization yet available, warns that that Hypercium has a potential for causing photoxicity, and that there might be an interaction between Hypercium and MAO inhibitors. Herb World News Online, www.herbs.org/current/stjstandard.html, mentions the possibility that there is more than one compound responsible for the antidepressant effectiveness of St. Johnís Wort. The site says that one study has found that Hypercium inhibited the uptake of serotonin, dopamine, noradrenaline, GABA, and L-glutamate, and cites the study. Overall, the purpose of the above organizations is to give out information that is valid. They mention side affects and seem to avoid making wild claims. One must still proceed with caution because these web sites may want to promote the use of herbs, and might therefore construe the facts. Special care should be taken if a site seems to endorse a certain product, because the organization may be getting paid to lend support to the product.
Go Ask Alice, www.goaskalice.columbia.edu/1348.edu, is a part Columbia Universityís Health Education Program. Endorsed by a university, especially a world renowned university, adds to the legitimacy of a site. On this web page, Alice talks about how the herb may work, its side effects such as increased sensitivity to sunlight and allergic reactions, and that the Hypercium is not regulated by the FDA. She warns that pregnant women and those who are breast-feeding should not use it, and that anyone who wants to try the herb, should contact their physician first. She says that no research has been done on the herbs long-term safety and efficacy, and the NIMH, NIH, and ODS have recently launched a large-scale clinical trial. This is the first web site that I have found that gives a brief, but comprehensive look at Hypercium. She is not getting paid to sell something, instead her job is to provide consumers with information that may improve their lives.
What Science Says About St. Johnís Wort
There have been two large meta-analysis of clinical trials on the effects of Hypercium on depression. In the first, Linde, et al. (1996) reviewed 23 randomized clinical trials, with a total of 1757 subjects, that compared extracts of hypercium with placebo or another treatment in depressive patients. The researchers concluded that there is good evidence that hypercium is better than placebo in treating some depressive disorders, and that the evidence they have found is inadequate to establish whether hypercium is as effective as other antidepressants. Furthermore, hypercium seems to have fewer short term side affects than other antidepressants, and when they do occur they are very mild (Linde, et al., 1996).
This study had several problems though. The biggest problem that I have found is that although most studies stated that patients suffered from mild to moderately severe depression, the statement did not always correlate with the severity of symptoms according to the Hamilton depression scale. Furthermore, hypericin may not be the only active chemical in hypercium and therefore different hypercium preparations vary in their content. Daily doses of the extract and amount of total hypercin varied among trials. Many of these problems are common to all studies on hypercium.
A second meta-analysis by Kim, Streltzer, and Gobert (1999), attempted to correct the faults in the Lindeís study, and as a result, their conclusion differed. They included only well-defined clinical trials that were controlled, double-blind, and used strictly defined depression criteria (the Hamilton depression scale) that were analyzed by the rate of change of depression and by the number of treatment responders. They used six studies that included a total of 651 outpatients, and even though they used fewer studies, the researchers felt that their more stringent inclusion criteria increased the validity of the meta-analysis. They found that hypercium was more effective than placebo and similar in effectiveness to tricyclic antidepressants. They conclude because many of the studies included have design problems, they cannot definitely state that hypercium is an effective anti-depressant (Kim, Streltzer, and Gobert, 1999),. I feel this meta-analysis is more critical of procedures, and is therefore more valid when assessing the safety and effectiveness of hypercium. It is interesting to note that none of the advertisements cited this study, while a few did cite the Linde, et al., study. They are not giving the consumer all the information needed to make a well informed decision on whether or not take the drug.
Some of the advertisements claimed that hypercium is comparable in effectiveness to tricyclics such as imipramine and amitriptyline, and for the most part this is in fact true. Two studies have shown that hypercium is as effective as imipramine. Additionally, both studies conclude that patients tolerate the hyercium extracts better than they do the tricyclic antidepressants, and therefore by improving the patientsí compliance, hypercium is a promising drug for long term treatment (Phillip, Kohnen, and Hiller, 1999; Vorbach, Arnoldt, and Hubner, 1997). Vorbach, Arnoldt, and Hubner (1997) looked at severe depressive episodes and still found hypercium as effective as imipramine (Vorbach, Arnoldt, and Hubner, 1997). The problem with this study is that they did not have a placebo group and so therefore we cannot definitively conclude whether or not the effect was due to the drugs or a third factor. Another study compared hypercium and amitriptyline and found the two comparable in effectiveness. The authors concluded that because patients who were taking hypercium exhibited fewer side affects, hypercium is more advantageous in that there is more compliance (Wheatley, 1997).
Hypercium has also been found to be effective in treating seasonal affective disorder (SAD). In a four week treatment study of 20 SAD patients, hypercium was associated with a significant reduction in the total score of the Hamilton Depression Rating Scale. Hypercium was found to be to be well tolerated and therefore the data suggest that hypercium may be an efficient therapy in patients with SAD. Again there was no placebo group, and the researchers conclude that there needs to be further controlled studies to substantiate the result (Kasper, 1997). As odd as it is, none of the web sites mentioned that hypercium may help SAD.
Another study examined the antidepressant-like effects of hypercium on the sleep polysomnogram. The researchers administered hypercium to healthy subjects using a placebo-controlled, cross-over design, and studied their sleep polysomnograms. Hypercium appeared to significantly increase the latency to rapid eye movement (REM) sleep. The researchers conclude that their data is consistent with the proposed clinical antidepressant efficacy of hypercium, and raise the possibility that its pharmacological mechanism of action may be similar to that of conventional antidepressant medication (Sharpley, McGavin, Whale, and Cowen, 1998). Many of the advertisements that I have found on the web say that hypercium definitely helps sleep and fights insomnia. The study by Sharpley, McGavin, Whale, and Cowen (1998) mentions nothing about hypercium ameliorating sleep problems. They only speak about a correlation and say that there needs be more studies to explore the effect.
The mechanism of the antidepressant activity of hypercium is not yet understood. Muller, Rolli, Schafer, and Hafner (1997) looked at several biochemical models. They were able to confirm several previous reports of a weak potency of hypercium as an inhibitor of monoamine oxides A and B activity. They found that the weak activity of the hypercium extract does not suggest that monoamine oxidase inhibition explains the antidepressant effect. However, they found that hypercium acts as an inhibitor of serotonin, norepinephrine, and dopamine. They conclude that taken together, hypercium extract seems to be active in biochemical systems which are also relevant to explain the pharmacological properties of tricyclic antidepressants and specific serotonin reuptake inhibitors (Muller, Rolli, Schafer, and Hafner,1997). Several other studies have found comparable results as well (Muller, et al., 1998; Neary and Bu, 1999). The problem with these studies is that all use rats, and therefore there is a limit to how much we can generalize the findings to humans. A study by Franklin, et al. (1999), found that hypercium may increase some aspects of brain dopamine function in humans (Franklin, et al., 1999). So there is a definite possibility the findings in rats may apply to humans as well.
The web sites that advertised hypercium to be a monoamine oxidase inhibitor were wrong. But they may be right about the effect of hypercium on serotonin, norepinephrine, and dopamine. I find it interesting that they never mention that most of the documented results are in animal models. People would be less likely to buy the product if this was the case, and so once again they are not showing a clear picture of hypercium.
The side affect mentioned most by scientific articles and the Go Ask Alice web site, www.goaskalice.columbia.edu/1348.edu, is that hypercium increases sensitivity to sunlight. A study by Brockmoller, et al. (1997) found that UV sensitivity was not or only marginally increased. The researchers conclude that although they found that hypercium does not promote photosensitivity in humans, though higher doses of hypercium and different hypercium extracts may differ (Brockmoller, et al., 1997).Until very recently, most scientific studies about hypercium report that there are few if any side effects. The few times side effects are mentioned, theyíre minimal, and the researchers conclude that this property of hypercium will promote compliance (Linde, et al., 1996; Kim, Streltzer, and Gobert, 1999). In the February 11, 2000 issue of The Lancet , www.thelancet.com, a study is presented in which hypercium significantly reduces the plasma concentration of indinavir, an HIV drug, when the two are taken together. The effect of cyclosporin, a transplant drug used to suppress patientsí immune systems so their bodies donít reject the new organs, was found to be greatly reduced. Before these reports, there were no scientific studies that showed such important contraindications, though there were several studies that warned that there has not been enough research done to call hypercium safe.
What is bothersome is the fact that there are advertisements out there that say that hypercium is proven to be safe. Obviously, science does not know enough, and the advertisements are making people think that this is a safe drug. Additionally, there were effects the advertisements mentioned to which I could not find support for. Effects such as curing anxiety, apathy, and anorexia seem to be unsupported by scientific literature.
Scientific research has for the most part shown that hypercium does have an antidepressant effect and that it may work like other antidepressants with minimum side effects. Authors of the studies warn that there has not been enough research to definitively show that hypercium is a safe and effective drug. The advertisements and other web sites for the most part do not give an accurate account of scientific study, and therefore the information they give is not always totally accurate. They construe the empirical evidence to further their own means, and therefore the consumer needs to be wary of any incredible claims. Better packaging needs to be made to warn consumers, and more studies need to be done, because although hypercium seems to be effective we do not yet know everything about it.
1) Brockmoller, J., et al. (1997). Hypericin and Pseudohypericin: Pharmakinetics and Effects on Photosensitivity in Humans. Pharmacopsychiatry, 30, 94-101.
2) Cracchiolo, Camilla. (1999). St. John's Wort Literature Review. www.primenet.com/~camilla/STJOHNS.FAQ.
3) Franklin, Mike., et al. (1999). Neuroendocrine Evidence for Dopameninergic Actions of Hypercium Extract (LI 160) in Healthy Volunteers. Biological Psychiatry, 46, 581-584.
4) Kasper, S., et al. (1997). Treatment of Seasonal Affective Disorder (SAD) with Hyercium Extract. Pharmacopsychiatry, 30, 89-93.
5) Kessler, R. C., et al. (1994). Lifetime and 12-month prevalence of DSM-IIIR psychiatric disorders in the United States. Archives of General Psychiatry, 51, 8-19.
6) Kim, H. L., et al. (1999). St. Johnís Wort for Depression: A Meta-Analysis of Well-Defined Clinical Trials. The Journal of Nervous and Mental Disease, 187(9), 532-538.
7) Linde, K., et al. (1996). St. Johnís Wort for depression Ė an overview and meta-analysis of randomized clinical trials. BMJ, 313, 253-258.
8) Muller, W. E., et al. (1997). Effects of Hypercium Extract (LI 160) in Biochemical Models of Antidepressant Activity. Pharmacopsychiatry, 30, 102-107.
9) Neary, J. T., and Yurong, B. (1999). Hypercium LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes. Brain Research, 816, 358-363.
10) Phillips, M., Kohnen, R., and Hiller, K. O. (1999). Hypercium extract versus imipramine or placebo in patients with moderate depression: randomized multicentre study of treatment for eight weeks. BMJ, 319, 1534-9.
11) Sharpley, A. L., et al. (1998). Antidepressant-like effect of Hypercium perforatum on the sleep polysomnogram. Psychopharmacology, 139, 286-287.
12) Vorbach, E. U., Arnoldt, K. H., and Hubner, W. D. (1997). Pharmacopsychiatry. Efficacy and Tolerability of St. Johnís Wort Extract LI-160 Versus Imipramine in Patients with Severe Depressive Episodes According to ICD-10. Pharmacopsychiatry, 30, 81-85.
13) Wheatley, D. (1997). LI-160, an Extract of St. Johnís Wort, Versus Amitriptyline in Mildly to Moderately Depressed Outpatients Ė A Controlled 6-Week Clinical Trial. (1997). Pharmacopsychiatry, 30, 77-80.
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