St. John’s wort. St. John’s wort (Hypericum perforatum) is a medicinal herb used for the treatment of neurological and psychiatric disorders, including depression (Nangia M et al 2000). Compared to placebo, H. perforatum extract can effectively treat mild to moderate depression, reducing symptoms and recurrence rate (Lecrubier Y et al 2002).
The mechanism of action of St. John’s wort in depression is not entirely clear. One idea is that St. John’s wort affects presynaptic serotonin uptake and inhibits norepinephrine re-uptake (Nangia M et al 2000). By affecting or inhibiting reuptake mechanisms of presynaptic neurons, St. John’s wort may increase availability of serotonin and norephinephrine. Clinical trials show positive response rates to treatment with St. John’s wort (Kim HL et al 1999; Linde K et al 1996). Please see the important safety information on St. John’s wort at the end of this chapter.
In January 1997, we carried a story on hypericum (St. John’s Wort), an herbal extract used extensively in Germany to treat depression. On June 27, 1997 ABC-TV program “20/20” featured an extremely favorable story about St. John’s Wort that has caused a run on health food stores for this “new” natural antidepressant. The ABC report featured psychiatrist Harold Bloomfield, co-author of “Hypericum & Depression,” who said that St. John’s Wort is a good alternative to Food And Drug Administration-approved drugs for mild or moderate depression.
The report also featured interviews with patients who said they had improved dramatically with St. John’s Wort after failing to gain relief from antidepressant drugs. In recent weeks, there have been other stories about St. John’s Wort for depression in newspapers and magazines. In light of this media blitz, we present a short review of the subject.
Scientific Evidence
To date, there have been case reports and drug monitoring studies in more than 5,000 patients on the efficacy and safety of standardized St John’s Wort preparations. Twenty-three controlled double-blind studies have been conducted on more than 1,757 patients. Sixteen of these compared hypericum with placebo (sugar pills) and nine with standard reference treatments including Imipramine-2, Amitryptilin-2, Maprotiline-1, Desipramine-1, Diazepam-2 and light therapy.
In most of these studies, both depressive symptoms (depressed mood, anxiety, loss of interest, feelings of low worth, decreased activity) together with secondary symptoms (sleep disturbance, lack of concentration, bodily complaints such as fatigue) showed general clinical improvement, ranging from 50 to 80 percent when compared to low- to medium-dose treatment with “classic” synthetic anti-depressants.
In a German study by 663 private practitioners on 3,250 patients (76 percent women and 24 percent men), the percentage of patients who showed improvement in depressive and secondary physical symptoms (ranging from fatigue, cardiac, digestive and sleep disorders, to generalized pain) was similar to previous studies, with about 80 percent of patients feeling better and only 15 percent unchanged or worse. In these studies, St. John’s Wort was significantly superior to placebo and similarly effective as standard antidepressants, with significantly fewer side effects.
Dosage and Indications
Although St. John’s Wort is available without a prescription, it should be used for clinical depression under the care of a physician. The evidence shows that St. John’s Wort is effective only for mild or moderate depression and should not be relied on for severe depression.
The evidence also shows that St. John’s Wort is slow-acting, and that it can take up to six weeks before it begins to relieve depression. Anyone seeking a fast-acting alternative to antidepressant drugs should consider S-adenosylmethionine (SAMe), which has been shown to have potent antidepressant effects in a week or less in some studies.
The most commonly used dose of St. John’s Wort for depression is 300 mg, three times a day for four to six weeks. If benefits are found after this period, the dosage is usually reduced somewhat. If you already are taking prescription antidepressants, do not alter your dosage or combine with St. John’s Wort without first consulting with your doctor.
St John’s Wort should not be used with MAO (monoamine oxidase) inhibitors such as Nardil or Parnate. There is some evidence that at least part of the action of St. John’s Wort is as a serotonin uptake inhibitor (SRI). Combining an SRI with a MAO inhibitor can cause a dangerous rise in blood pressure.
For further information we recommend the book “Hypericum & Depression” by Harold Bloomfield, M.D., Mikael Nordfors, M.D. (With Peter McWilliams).
A survey released at the annual American Academy of Family Physicians meeting in San Francisco revealed that one in three primary care doctors recommend herbal supplements to patients on a weekly basis. And the herbal supplement doctors have found most useful and effective is St John’s wort, a mood stabilizer that may help treat minor depression.
The survey, conducted by Pharmaton Natural Health Products, also found that physicians are practicing what they preach: On average, 28 percent of doctors use herbal supplements themselves.
According to a survey conducted by addiction researchers at the University of North Carolina, alcoholics also may benefit from St. John’s wort. Both alcoholism and depression have been linked to a deficiency of serotonin in the brain. Researchers in the study speculate that hypericin, St. John’s wort’s main active ingredient, may ease alcohol addiction as it does depression: by increasing serotonin levels in the brain. Further, St. John’s wort may also influence dopamine and gamma-aminobutyric acid (GABA), neurotransmitters that may be key in alcohol addiction.
However, a word of caution: The possibility exists that St. John’s wort may cause further complications when taken with alcohol or any other drugs.
A Botanical Alternative To Antidepressant Drugs (By I. J. Wolf)
In Hypericum & Depression, Dr. Harold Bloomfield (and co-authors Mikael Nordfors, M.D. a nd Peter McWilliams) note that St. John’s Wort has long been used in folk medicine as a powerful antibacterial and antifungal remedy. They cite Rodale’s Illustrated Encyclopedia of Herbs for evidence that hypericum has been a tool to relieve ulcers, gastritis, diarrhea and nausea, as well as a balm for cuts, and an analgesic.
For decades, millions of Americans seeking relief from clinical depression have had limited treatment options: sufferers might work with a therapist, or try antidepressant drugs like Prozac or Zoloft. While these approaches have a credible track record, they have drawbacks.
A Natural Option
In the early 1990s, Bloomfield and McWilliams, co-authored a book How to Heal Depression. In the course of their research they came across wide-ranging (often unverified) alternatives to standard treatments for depression. Among these was Hypericum Perforatum or St. John’s Wort (wort means plant)-an herbal extract from a flowering botanical, long known for its medicinal properties.
“Hypericum isn’t something they’ve just discovered across the Atlantic. It’s been used by European and German physicians in a continuous pattern since ancient times,” says Dr. Bloom- field. “It comes as a surprise to us here in the U.S. because we’ve chosen to sever our roots to herbal medicine.”
At the same time, studies examining the effect of hypericum on depression began to appear in medical literature such as the British Journal of Medicine. These studies suggested that one or more of the active ingredients in the botanical extract (possibly hypericin) was as effective in alleviating the symptoms of depression as synthetic pharmaceuticals, with fewer side effects. This led them to write their current book Hypericum & Depression, just published by Prelude Press.
Scientific Validation
The results of 23 studies involving five thousand participants led the British Medical Journal to editorialize that: “St. John’s wort is a promising treatment for depression…Hypericum extracts were significantly superior to placebo and similarly effective as standard antidepressants…The herb may offer an advantage, however, in terms of relative safety and tolerability, which might improve patient compliance.”
In October 1994, the Journal of Geriatric Psychiatry and Neurology also editorialized about hypericum in a supplemental issue devoted entirely to papers exploring the herb as antidepressant. According to editor Michael A. Jenike, M.D:
“The many studies form an impressive body of evidence…treatment with hypericum has been confirmed [to have] similar effectiveness (50 to 80 percent) as synthetic antidepressant drugs. Its mild side-effect profile may make it the first treatment-of-choice for mild-to-moderate depression…”
Hypericum Vs. Antidepressant Drugs
There have been at least 8 randomized, double-blind studies comparing hypericum with antidepressant drugs such as imipramine, amitryptilin, maprotiline and desipramine in patients with mild-to-moderate de-pression. In general, hypericum has produced similar antidepressant effects that become stronger with the length of treatment, without the adverse side effects associated with these drugs. Here are the results of two of these studies.
In a study at the Psychiatric Clinic in Darmstadt, Germany, 135 patients, age 18-75 years (71 males and 64 females) were given indistinguishable tablets of hypericum extract (2.7 mg. daily of standardized hypericin content) or imiprimine (75 mg. daily) in three divided doses for 6 weeks in a randomized, double-blind clinical trial. Two of the measures of depression used in this trial were the Hamilton Depression Scale (HAMD) and the Clinical Global Impressions (CGI) scale.
The mean HAMD fell from 20.2 to 8.8 in the hypericum group and from 19.4 to 10.7 in the imipramine group. The CGI score for therapeutic effect rose from 1.3 to 3.1 in the hypericum group and from 1.2 to 2.7 in the imipramine group. Based upon the CGI scores, the researchers concluded that: “The CGI score on change of illness severity showed a trend towards better results with hypericum. 81.8% were classified as having improved on hypericum, while 62.5% improved on imipramine. 18.2% were unchanged or the same on hypericum compared to 34.4% in the imipramine group. None of the hypericum patients and two of the imipramine patients experienced worsening of their condition.”
Adverse drug effects were reported by 8 patients on hypericum and 11 patients on imipramine. The most frequent adverse effects in the hypericum patients were dry mouth and dizziness compared to dry mouth, dizziness, anxiety and constipation in the imipramine group. Ten of the 11 adverse side effects reported by the hypericum patients were considered to be “mild”, while in the imipramine patients, 15 were considered “mild”, 4 “moderate” and 3 “severe”.
Another randomized, double-blind study compared hypericum (75 mg daily of standaridized hypericin) with amitryptiline (30 mg. daily) in three divided doses for 6 weeks in 80 patients with mild-to- moderate depression (Neurologie/Psychiatrie, 7:235-240, 1993). In this study, the HAMD score fell from 15.82 to 6.34 in the hypericum group and from 15.26 to 6.86 in the amitryptiline group.
In this study, there were more than twice as many complaints about ad-verse side effects in the Amitryptiline group (58%) than in the hypericum group (24%). The side effects in the Amitryptiline group, which included gastrointestinal and respiratory problems, were more serious than in the hypericum group.
Hypericum Vs. Placebo
There have been at least 16 randomized, double-blind studies comparing the antidepressant effects of hypericum with placebo. In 13 of these studies, there was a statistically significant advantage for hypericum over placebo. In a summary of 15 of these studies in 1,008 patients, there was no reported difference in adverse side effects in the patients receiving hypericum (4.1%) and the patients receiving placebos (4.8%). There were actually fewer patients who dropped out of the hypericum groups (0.4%) than from the placebo groups (1.6%).
In a multi-center placebo-controlled trial, 72 patients, age 18-70 years, with “major depression” were given 2.7 mg hypericum (standardized hypericin content) daily or placebo in three divided doses for 6 weeks. In the last two weeks of the study, the patients in the placebo group were given hypericum because of the obvious advantage of hypericum over placebo.
The scores on the HAMD showed a clearcut, statistically significant benefit for hypercium vs. placebo. The mean score in the hypericum group fell from 21.8 to 9.3 (within the normal range) after 4 weeks of treatment, with a further reduction to 6.3 in weeks 5 and 6 of the trial. In comparison, the placebo group also showed reduced scores, but not to normal levels.
According to the CGI scale, there was major therapeutic improvement in the hypericum group compared to only mild improvement in the placebo group. In the last two weeks of the study, when those in the placebo group were given hypericum, there was “noticeable improvement” (according to the CGI scale). There were few or no side effects reported in the hypericum group.
Other Benefits Of Hypericum
According to the book Hypericum & Depression, the authors note that the herb “is currently being medically studied as a treatment for AIDS, several forms of cancer, skin diseases such as psoriasis, rheumatoid arthritis, peptic ulcers, and even hangover.”
Hypericum also seems to improve the quality of sleep, a major concern in depressed patients. Early studies on subgroups of depressed populations reveal that St. John’s Wort may yield beneficial results when used as treatment for Seasonal Affective Depression (SAD) and other forms of depression.
How Hypericum Works
Early on, there was speculation that hypericum may prevent the breakdown of neurotransmitters by enzymes such as monoamine oxidase (MAO). This explanation had the herb cast in the role of a MAO inhibitor. Further study, however, has called this theory into question.
A more probable scenario is that one out of about ten possible components in hypericum blocks the binding of serotonin and other neurotransmitters.
Another possibility is that hypericum boosts the immune system by blocking the production of stress-induced hormones such as CRH, ACTH and Cortisol. This action may validate the herb’s proposed antiviral properties.PK: By the way, we much prefer that people take natural products, such as St. John’s Wort, rather than prescription pharmaceuticals for depression. In times of great stress we have taken it ourselves, and everybody we have recommended it to has had positive results. Besides, the antidepressant effect of St. John’s Wort is very well documented, both in this country and in Europe, especially Germany. In Germany, for instance, doctors prescribe St. John’s Wort five times more often than any other anti-depressant.
EK: The same goes for passionflower, in case of anxiety. It works as well as or better than prescription medications and leaves the mind perfectly clear. And it does not appear to have any side effects. It also works wonders for insomnia, if taken a little before bedtime, and
Adverse Side Effects
“Hypericum is very very safe,” says Bloomfield. "In Germany, 66 million doses were prescribed daily in 1994. There were no reports of negative drug interaction and no evidence of toxicity or overdose.
In a study of 3,250 patients taking the herb, 2.4% experienced side effects, usually mild. Gastrointestinal irritations accounted for 0.6%, allergic reactions for 0.5%, tiredness for 0.4% and restless-ness for 0.3%.
The British Medical Journal reported a higher figure: 10.8 percent, with complaints similar to those above.
“Even at this higher rate”, notes Bloomfield, The British Medical Journal reported a higher figure: 10.8 percent, with complaints similar to those above. “Even at this higher rate”, notes Bloomfield, “the medical publication concluded that the herb’s serious side effects were ‘rare and mild’”.
Dr. Bloomfield observes that most of the side effects noticed with hypericum disappear on their own as the body acclimates itself to the herb, and may also be improved with a slight reduction in dosage. Bloom-field also advises the user to stay in communication with his/her healthcare provider and, if the symptoms remain severe, discontinue the therapy and try another approach.
Recommended Dosage
Based upon the majority of the medical studies on hypericum and depression, Bloomfield recommends 300 mg of hypericum extract (containing 0.3% standardized hypericin) three times a day for depression. The adult dosage may be taken by adolescents.
Bloomfield cautions that the herb may not work for six-to-eight weeks. Testimonials have recorded results in shorter periods of time.
Regarding how long a time to continue on hypericum, Bloomfield estimates a likely maintenance dose of six months. “Though it’s generally a 1/3, 1/3, 1/3 situation,” he continues: “A third of those taking hypericum will be fine after six months and can wean themselves off the herb; another third may find they want to use it intermittently as needed; while the last third may feel best continuing on the herb for longer period of time.”
Important Cautions
Bloomfield stresses that anyone currently taking standard antidepressant drugs should not change their regimen suddenly without professional supervision. Abrupt discontinuation of such drugs risks a potentially dangerous rebound effect. As with any serious illness, anyone suffering from clinical depression should be followed by a qualified psychiatrist or other physician with experience in treating depression.
Also, combining hypericum with MAO inhibitors might produce a dangerous rise in blood pressure. Unsupervised self-medication with hypericum in combination with antidepressant drugs can cause serotonin syndrome-an excess of the neurotransmitter. Symptoms of this syndrome include sweating, agitation, confusion, lethargy, tremor and muscle jerking.
Bloomfield does not recommend hypericum for severe depression or bipolar (manic-depressive) illness until more research is conducted in the use of hypericum for these conditions.