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Life Extension Magazine

LE Magazine April 1997

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.

image 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.

image 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.

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.