St. John’s Wort

Michael Clark

Hypericum What is St. John’s Wort?

St. John’s Wort (Hypericum Perforatum) is a small plant with bright yellow flowers. Wort is an old English term that means plant. The red spots on the leaves of the plant are symbolic of the blood of St. John after his beheading. The plant is grown worldwide but it grows especially well in parts of Northern California and Southern Oregon (http://www.doctormurray.com/articles/worteditorial.htm).

St. John’s Wort has not been well known in the United States until recently. Studies on the medicine have been going on for decades in Europe. German doctors have been prescribing it and the insurance companies have been paying for it. It is available in many health shops in the United States and all across Europe but recently it has been selling out because of its increased popularity. In the United States, manufacturers can’t advertise it as a treatment for depression and doctors can’t prescribe it because the FDA (Federal Drug Administration) won’t allow it. It has to be advertised as a contribution to emotional balance and positive outlook or promoting a sense of balance for people with mild depression, not severe or major depression. St. John’s Wort comes in one of three forms: liquid, capsule, and dried form. (http://www.vanderbilt.edu/AnS/psychology/health_psychologyStJohn.htm)

What

What is the purpose of St. John’s Wort?

St. John’s Wort use for depression, insomnia, and anxiety inspired a group of German doctors in the 1980’s to do research on the herb. The findings of their studies brought the group fame in the late 1990’s. A number of studies indicate that St. John’s is an effective treatment for treating mild-to-moderate depression (http://www.mothernature.com/cg/stjohns.asp).

St. John’s is quickly becoming the most popular herbal drug in the United States. German physicians prescribed a total of 66 million daily doses in 1994. These German physicians now prescribe St. John’s wort an average of 8 times more than Prozac. These doctors claim that St. John’s wort produces better results in relieving depression, but the medicine does not have near the amount of side effects as Prozac (http://www.doctormurray.com/articles/worteditorial.htm).

How does St. John’s Wort work?

Originally, scientists thought that the reason St. John’s worked as an antidepressant was due to a substance called hypericin. Hypericin is antiviral and is also thought to be mood brightening. Hypericin acts as an inhibitor of the enzyme monoamine oxidase, a bodily chemical associated with depression, thereby resulting in an increase of CNS monoamines such as serotonin and dopamine. A new study has shown that St. John’s Wort interacts with a link between the immune system and mood. The immune system and the nervous system share many common biochemical features. Changes in the serotonin, dopamine, or melatonin levels in the body may cause St. John’s effect on the nervous system (http://www.doctormurray.com/articles/worteditorial.htm).

Another study suggests that the antidepressant effects may result from a mixture of several pharmacologic mechanisms similar to prescription antidepressants, including monoamine oxidase inhibition, blockade of muscarinic cholinergic receptors, and inhibition of γ-aminobutyric acid (GABA), norepinephrine, dopamine, and serotonin. Additional antidepressant activity may also occur through opposition of σ receptors in the limbic system, an area of the brain connected with regulation of emotions (Beckman, Sommi, Switzer 2000).

There are only a few side effects in St. John’s Wort. The most common side effects from taking St. John’s Wort include nausea, stomachache, lack of appetite, and tiredness. A small amount of people who take high doses of St. John’s Wort may experience skin reactivity to light from the sun. Pregnant women also should not take it. The effect that the herb has on the nervous system remains unclear and most experts recommend against taking it with some other forms of anti-depressants like Prozac or Zoloft. Also, St. John’s Wort greatly reduces the effectiveness of anti-HIV protease inhibitors and the organ transplant drug cyclosporin. It should not be taken with any type of these drugs (http://www.mothernature.com/cg/stjohns.asp). Some of the other drugs that St. John’s should not be taken with are Indinavir, Warfarin, Oral contraceptives, Digoxin, and Theophylline (Mehta 2000).

There are many potentially serious drug interactions between St. John’s Wort and several other prescription medicines. Many of these interactions are the result of induction by St. John’s Wort of various drug-metabolizing enzymes including the cytochrome P450 system and possible also P-glycoprotein. This could result in decreased blood levels and therapeutic effect of medicines metabolized by these enzymes (Mehta 2000).

St. John’s Wort affects the neurotransmitters in the brain. This might result in drug interactions between St. John’s Wort and certain psychotropic medicines including the selective serotonin reuptake inhibitors (SSRIs). St. John’s Wort may also interact dangerously with drugs used to treat migraines (sumatriptan, rizatriptan, etc.). Elderly patients are more susceptible to the serotonin syndrome and may develop a more serious reaction (Mehta 2000).

What claims are made about the effectiveness of St. John’s Wort?

It is said that St. John’s Wort is more effective than a placebo for treating mild to moderately severe depression. This evidence comes from an analysis of all studies in which a depressed person was randomly given either a placebo or St. John’s Wort. According to Michael T. Murray:

“There have been over 25 double-blind studies with St. John’s wort extract in the treatment of depression. The methodological quality of this research, particularly the studies since 1989, has been judged as being acceptable by strict criteria. The overall results have also been judged as providing good documentation of antidepressant activity” (http://www.doctormurray.com/articles/worteditorial.htm).

What evidence is offered in support of St. John’s Wort?

At least one out of every 20 Americans gets depressed each year. They rely on anti-depressants to help them deal with their depression. A new study shows that St. John’s is just as effective with fewer side effects. In the August 3, 1996 issue of the British Medical Journal it contains 23 studies that suggests St. John’s Wort is just as helpful as commonly used anti-depressants. In these 23 studies, there were one thousand seven hundred and fifty-seven outpatients with mild or moderately severe depression. Fifteen of the studies were placebo controlled and eight of them compared St. John’s Wort with another drug treatment. The treatment and observation period in all the studies were from periods of four to eight weeks. The trials were performed by psychiatrists (9 of the trials), internists (7 trials), general practitioners (6 trials), and obstetricians (1 trial). Twenty of the trials were double blind, one was single blind, and two were open (Linde, Ramirez, Mulrow, Pauls, Weidenhammer, and Melchart, 1996).

St. John’s Wort extracts were considerably greater to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and likewise effective in standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were only two dropouts for side effects with St. John’s and seven with standard antidepressant drugs. Side effects occurred in 50 patients on St. John’s and 84 patients on standard antidepressants (Linde et al, 1996).

There is a sufficient amount of evidence from this trial to prove that St. John’s Wort is more effective than a placebo for treatment of depressive disorders, but it is not known whether it is more effective for certain types of disorders than others. The current evidence is inadequate to establish whether St. John’s is as effective as other antidepressants and if it has fewer side effects. Additional studies should be done to compare St. John’s Wort with other antidepressants in a well-defined group of patients. The studies were laid out the following way (Linda et al, 1996).

Trial	# Of patients	Diagnoses	Compared Treatment	Total hypercin/ Day (mg)	Extract/day In (mg)	Duration of Treatment
Halama 1991	50	Neurotic depression, adjustment disorder	Placebo	1.08	900	4
Hansgen 1994	72	Major Depression	Placebo	2.7	900	4
Hubner 1994	40	Neurotic depression, adjustment disorder	Placebo	2.7	900	4
Lehrl 1993	50	Neurotic depression, adjustment disorder	Placebo	1.08	900	4
Harrer 1994	102	Single moderately severe depressive episode	Maprotiline 75 mg	2.7	900	4
Vorback 1994	135	Major depression Neurotic depression	Imipramine 75 mg	2.7	900	6
Werth 1989	30	Reactive depression after informing patients of necessity of amputation	Imipramine 50mg	.75	500	2

Another study on the effect of St. John’s Wort takes 263 moderately depressed people and distributes them St. John’s Wort, Imipramine (another anti-depressant), and a placebo. The patients took three capsules a day of one of the three pills that were all made to taste and look the same. After eight weeks of the experiment, the doctors distributed a survey, which is meant to measure the degree of the patient’s depression. St. John’s Wort eased depressive symptoms significantly more than the placebo and about the same as the Imipramine. Both drugs improved the patient’s score on the survey that gauged the quality of life. According to the researchers of the experiment, “St. John’s Wort extract may thus be considered as an alternative first choice treatment in most cases of mild to moderate depression without psychotic symptoms (http://webmd.lycos.com/content/article/1728.53357).

There are major studies that are set to begin in the fall of 2000. McLean Depression & Anxiety Disorders Outpatient Service will do one of the studies in which it will conduct a double blind and placebo controlled trial of AlterraTM, a new extended release form of St. John’s Wort, in 80 depressed outpatients. Another significant study, sponsored by the National Institute of Mental Health will be a three-year, 4.3 million-dollar study. This study will compare St. John’s Wort to Zoloft and a placebo. Three hundred and thirty-six patients will be selected from across the country to participate.

(http://www.selfgrowth.com/articles/ewing.html).

Who is presenting this information and why?

There are several different people that are presenting information about St. John’s Wort. Naturally, online herbal shops are presenting the information in order to sell it. But there are also web pages of people who were in depression but St. John’s Wort helped them work through it. There were many news articles about the herb, the safety of it, effectiveness it has in depressed patients. The medical journals presented a lot of studies done to show the effectiveness of St. John’s Wort.

Summary

According to David Menkes, “Hypericum extracts are effective in mild to moderate depression and may also be effective in severe depression if titration about the usual dose is allowed.” The main advantage of people taking it is their tolerability. Side effects are considerably mild and there is no sexual dysfunction like many other anti-depressant drugs (Menke 2000).

Based on all the evidence that I gathered. St. John’s Wort seems to be a good alternative anti-depressant medication. It seems to work best on those patients that are mild to moderately depressed. Its effectiveness on those patients with severe depression is yet to be determined.

Works Cited

Beckman, S., Sommi, R., Switzer, J. (2000). Consumer Use of St. John’s Wort: A Survey on Effectiveness, Safety, and Tolerability. Pharmacotherapy, 20, 568-574.

Linde, K., Ramirez, G., et al. (1996). St John's wort for depression---an overview and meta-analysis of randomised clinical trials. British Medical Journal, 313, 253-258.

Mehta, Ushma. (2000). Potentially Serious Drug Interactions Between St. John’s Wort And Other Medicines. South African Medical Journal, 90, 698.

Menke, David B. (2000). The Herbalist Will See You Now. British Medical Journal 320, 1142.

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