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Cancer Treatment Side Effects & Supportive and Palliative Care

St. John Wort

St. John's wort (Hypericum perforatum) is an herb native to Europe, West Asia, and North Africa, that has been used for centuries across Europe. The German Commission E (Germany's regulatory agency for herbs) describes the safety and effectiveness of the herb. Because of safety and effectiveness, St. John's wort was designated an approved herb by the Commission E in 1984, and it is available in Germany as a prescription for depression and anxiety.

The mechanism of action of St. John's wort seems to be related to the inhibition of the reuptake of serotonin, dopamine, and noradrenaline, along with activation of gamma-aminobutyrate and glutamate receptors.

RCTs of St. John's wort have shown that the extract is effective in treating mild to moderate depression in non-cancer patients, but results are mixed with regard to its effectiveness in treating severe depression. Some studies comparing St. John's wort to standard antidepressants suggest it may be as effective as imipramine or selective serotonin reuptake inhibitors (SSRIs) to treat mild to moderate depression. A recent review and meta-analysis of 37 double-blind randomized controlled trials that compared clinical effects of Hypericum with either placebo or a standard antidepressant in adults with depressive disorders reported that larger placebo-controlled trials restricted to patients with major depression showed only minor effects over placebo, while older and smaller trials not restricted to patients with major depression showed marked effects. Compared with standard antidepressants Hypericum extracts had similar effects. The authors concluded that the current evidence regarding Hypericum extracts is inconsistent and confusing.

A recent RCT involving 340 adult patients with major depression who were followed over a period of 2 to 6 months, compared the effects of St. John's wort, a placebo, and sertraline. The study showed that neither the St. John's Wort nor the sertraline group was any different from the placebo. This and similar studies suggest that St. John's wort may not be effective in moderate to severe depression, although this study was criticized because the approved antidepressant also showed no benefit.

Safety

Hypericin and hyperforin are the active constituents of St. John's wort, although other constituents have been identified, such as flavonoids that may also have antidepressant effects. Although St. John's wort extract is generally safe at doses of 400mg 3 times a day, interactions with drugs used in oncology care have been reported. For example, a recent pharmacokinetic study of the interaction between St. John's wort and imatinib mesylate (gleevec) showed that in healthy adult volunteers receiving a single 400-mg oral doses of imatinib before and after 2 weeks of treatment with St. John's wort 300 mg 3 times/day, the pharmacokinetics of imatinib were significantly altered by St. John's wort. Because therapeutic outcomes of imatinib have been shown to correlate with both dose and drug concentrations, the authors concluded that co-administration of imatinib with St. John's wort may compromise imatinib's clinical efficacy.

The most common adverse effect of St John's wort is transient photosensitivity. Other less common adverse effects include gastrointestinal upset, nausea, headache, constipation, dizziness, confusion, fatigue, and dry mouth Side effects reported appear less frequent than those triggered by standard antidepressants.

Recommendations

Because of the lack of evidence for St. John wort in oncology populations and possible interaction between this herb and chemo agents, St. John wort may be useful in patients who do not respond well to SSRIs but it is not recommended as a first line treatment.

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References - Hide References

  • Blumenthal M. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998, and Boston: Integrative Medicine Communications, 1998.
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  • Schrader E. Equivalence of St. John's wort extract (ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol 2000;15:61-8.
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  • Thiede HM, Walper A. Inhibition of MAO and COMT by hypericum extracts and hypericin. J Geriatr Psychiatry Neurol 1994;7(suppl 1):S54-6.