St. John’s Wort and Depression

By Gail Mornhinweg, PhD, ARNP, CS

The financial impact of depression, including treatment, disability, and lost productivity, has been estimated at $44 billion per year in the United States alone; worldwide, depression is the leading cause of disability.1

St. John’s wort (SJW) is the most widely used antidepressant in Germany1 and, according to the American Botanical Council, 1998 sales in the United States totaled more than $140 million, nearly a 190% increase over 1997 sales.2 Its over-the-counter availability and relatively low cost afford some relief to a large number of people with little or no health care.

Background and Historical Usage

St. John’s wort (Hypericum perforatum) has a very long and colorful history. Ancient Greeks believed that SJW had supernatural powers and its fragrance would cause evil spirits to fly away. Romans burned its leaves and flowers on Midsummer Day to rid evil spirits. The plant was later dedicated to the world of Christianity when it was recognized that it bloomed close to John the Baptist’s birthday (June 24).

SJW belongs to the Hypericaceae family and originated in Europe, Western Asia, and North Africa. SJW is an erect and bushy perennial herb that grows best in a sunny location in dry or chalky soil. The flowers have five, small yellow petals with tiny dots of reddish brown pigment. Of the more than 370 Hypericum species in the world, 25 are found in North America. The most commonly used parts are the leaves and flowering tops gathered during the blooming season.

SJW has been used in Europe for centuries to treat gastritis, wounds, kidney and lung problems, and insomnia. Today, SJW is most commonly used to treat symptoms of mild-to-moderate depression, anxiety, sleep disorders, and seasonal affective disorder.3-6 Other uses include neuralgia, sciatica, and indigestion. In topical form SJW promotes healing of wounds and burns and acts as an anti-inflammatory agent. Extracts have shown broad antibiotic activity against E. coli and S. aureus.7

Chemical Constituents

Chemical constituents of H. perforatum include hypericin, pseudohypericin, flavonoids, xanthones, phenolic carboxylic acid, essential oils, carotenoids, hyperforin, alkanes, phloroglucinol derivatives, phytosterols, and medium chain fatty acids.

Mechanism of Action

The mechanism of action for SJW’s antidepressant effects is still largely unknown. Some studies cite monoamine oxidase inhabitation (in vitro studies); others indicate the stimulation of g-aminobutyric acid (GABA) binding and synaptic uptake.8 The inhibition of serotonin reuptake also has been studied in vitro.9 Others indicate the downregulation of B-adrenoceptors,10 increased endorphin levels,11 and inhibition of benzodiazepine receptors.12

Others believe the flavonoids xanthone and quercetin may contribute to the effects in noradrenalin and serotonin metabolism.13 More recent studies indicate that hyperforin is the active agent responsible for SJW’s antidepressant effects.8

Clinical Research

Much of the data regarding the efficacy of SJW comes from a meta-analysis of 23 European studies.14 The results of this meta-analysis showed that the herb was more effective in treating depression than placebo and as effective as conventional tricyclic agents. A follow-up analysis of 27 studies published in 1997 demonstrated that there was no difference in response rates of individuals taking SJW compared to those taking antidepressants.15 Both analyses also indicated significantly fewer side effects with SJW use.

Because of its growing popularity and the results of previous trials, the National Institutes of Health has sponsored a three-year clinical study of SJW and its ability to treat major depression.1 Patients in this study will be randomized to receive 900 mg/d SJW, placebo, or a selective serotonin reuptake inhibitor (SSRI) for eight weeks. Subjects will be assessed with standard psychiatric evaluation tools and those who respond to treatment will receive 18 weeks of follow-up treatment.

Safety

SJW is considered safe when taken orally for medicinal purposes on a short-term basis. It is unsafe during pregnancy due to potential uterotonic effects and should not be used during lactation because of insufficient reliable information.16 There have been no scientifically reported deaths caused by SJW.16

Adverse Effects

Increased photosensitivity, manifested in itching and erythematous lesions, is possible in fair-skinned individuals taking large doses for extended periods of time; an SPF 15 sunscreen should be used by patients taking SJW.17 It is also recommended that patients taking SJW avoid tanning beds and sunlamps.

Other reports indicate mild abdominal discomfort, nausea, vomiting, dizziness, dry mouth, skin irritation, insomnia, elevated blood pressure, and unusual fatigue. There have been no reports of impaired driving or problems operating machinery associated with SJW use.18

Interactions

SJW may interact with L-dopa and 5-hydroxytryptophan. Concomitant use with other antidepressants increases the risk of serotonin syndrome and should be avoided.16

A recent study suggests an interaction between SJW and cyclosporin, indinavir, and other antiretro-virals.16,19,20 New information also indicates that hypericum extracts activate the P450 system, increasing elimination of some drugs from the body. SJW also may interact with other drugs metabolized by the P450 system, including calcium channel blockers, chemotherapeutic agents, antifungals, glucocorticoids, cisapride, losartan, fluoxetine, omeprazole, and fexofenadine.16,18,21

Concomitant use with other sedative herbs may enhance therapeutic and adverse effects.16 These sedative herbs include, but are not limited to, calendula, California poppy, catnip, capsicum, ginseng, German chamomile, goldenseal, hops, lemon balm, sage, skullcap, passionflower, stinging nettle, and valerian.

Although there have been no reports of interactions with tyramine-containing foods and large doses would most likely be required to produce an effect, the concern is often raised.16

Formulation and Dosage

SJW is available as a dried herb, liquid extract, tincture, infused oil, and as a tea. For mild-to-moderate depression, the most commonly prescribed oral dose is 900 mg/d standardized extract, dosed at 300 mg tid. Most products are standardized to 0.03% hypericin content; however, more recent studies indicate the use of hyperforin at 4-5%.8 The standardized dosage of hyperforin is 30-45 mg/d in divided doses.6 The Commission E monograph suggests an average daily dose of 2-4 g.22 It is suggested that treatment continue for at least four to six weeks to assess effectiveness. If symptoms do not improve by week 6 then a change is warranted.

Conclusion

In comparing the retail price of a month’s supply of conventional antidepressants (approximately $60) to the cost of SJW (approximately $15-30), SJW may represent a much more reasonable option for many patients. (For detailed pricing information, see Table 1.) It is a promising alternative to allopathic antidepressants, particularly for those who can not tolerate standard medicinals. Although the product is readily available, health care providers and patients need to be aware that there are other causes for the symptoms of depression, including thyroid disease and anemia. If symptoms are not alleviated, professional health care should be sought.

Table 1-Cost comparison: St. John's wort vs. conventional antidepressants
Product Name Generic/Latin Name Dosage Standardized 30-Day Supply
Paxil® paroxetine 10 mg/d n/a $59.59
Prozac® fluoxetine 10 mg/d n/a $67.20
Zoloft® sertraline 10 mg/d n/a $59.19
Kira Standardized Hypericum
   St. John's Wort Extract Hypericum perforatum 300 mg tid 3% hypericin $29.98
Movana™ Advanced
   St. John's Wort Hypericum perforatum 300 mg tid 3% hyperforin $24.98
Natrol St. John's Wort Hypericum perforatum 300 mg tid 3% hypericin $13.77
Nature's Way St. John's Wort Hypericum perforatum 300 mg tid 3% hypericin $14.99
Source: http://www.drugstore.com


Dr. Mornhinweg is an Adult Nurse Practitioner at the Choice to Heal Clinic in Floyds Knobs, IN.

References

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2. Blumenthal M. Herb market levels after five years of boom. HerbalGram 1999;47:64-65.

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4. Martinez B, et al. Hypericum in the treatment of seasonal affective disorders. J Ger Psychiatry Neurol 1994;7(suppl 1):S29-S33.

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8. Chatterjee S, et al. Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci 1998;63:499-510.

9. Mueller W, et al. Effects of St. John’s wort extract, LI-160, on neurotransmitter uptake systems and adrenergic receptor density. Paper presented at the Second International Congress on Phytomedicine. Munich, Germany; 1996.

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13. Cott JM. In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Pharmacopsychiatry 1997;30(suppl 2):108-112.

14. Linde K, et al. St John’s wort for depression—an overview and meta-analysis of randomised trials. BMJ 1996;313:253-258.

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16. Natural Medicines Comprehensive Database [online version]. Stockton CA: Therapeutic Research Center Inc.; 2000.

17. Brockmoller J, et al. Hypericin and pseudohypericin: Pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30:94-101.

18. Woelk H, et al. Benefits and risks of hypericum extract LI 160: Drug monitoring study with 3,250 patients. J Geriatr Psychiatr Neurol 1994;7(Suppl 1):S34-S38.

19. Piscitelli SC, et al. Indinavir concentrations and St. John’s wort. Lancet 2000;355:547-548.

20. NIH clinical center study demonstrates dangerous interaction between St. John’s wort and an HIV protease inhibitor. Available at: http://www.nih.gov/news/pr/feb2000/wgmce-10.htm. Accessed April 10, 2000.

21. Risk of drug interactions with St. John’s wort and indinavir and other drugs. Available at: http://www.fda.gov/cder/drug/advisory/stjwort.htm. Accessed April 10, 2000.

22. Blumenthal M. The Complete German Commission E Monographs. Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; 1998.