Scientific Names | Reported Uses | Scientific Evidence | Adverse Effects | References

Reported Uses:

• Historical reputation as a mild, short term anti-depressant.
  
• Anxiolytic.
  
• Possible anti-retroviral action.
  

Scientific Names | Reported Uses | Scientific Evidence | Adverse Effects | References

Scientific Evidence:

• In 1996, a meta-analysis was conducted on 23 randomized clinical trials designed to assess the efficacy of St. John's Wort on depression. In 10 of 13 placebo-controlled trials investigated, St. John's Wort was deemed superior to the placebo in eliciting an anti-depressant response in the trial participants. In three antidepressant-controlled studies, similar response rates were found in the St. John's Wort group as in the standard anti-depressant group.⁸ Many flaws in the studies have been pointed out since this meta-analysis was conducted. Only 2 of the aforementioned 16 studies enrolled participants who met DSM-IV criteria for major depressive disorder (MDD). The studies were also of short duration, lasting only four weeks for most trials.¹¹ Because of flaws like these, it would be hard to extrapolate a sustained therapeutic benefit of St. John's Wort on patients who suffer from a real depressive disorder.
  
• A 1998 placebo-controlled study tested the efficacy of two preparations of St. John's Wort extract that differed in the hyperforin content (0.5% hyperforin vs. 5.0% hyperforin). A decline in the Hamilton Depression Scale (HAMD) was significantly greater in the high hyperforin group when compared to the placebo controls. The low hyperforin group showed no significant difference in HAMD decline when compared to placebo controls.⁶ If the anti-depressant activity of St. John's Wort is real, this study points to the importance of standardizing St. John's Wort extract for hyperforin content when considering it as a therapeutic agent.
  
• To address some of the shortcomings of previous clinical trials (subjects with differing levels of clinical depression, lack of placebo controls, lack of SSRI controls, short duration of study), a study was published in 2002 which tested the efficacy of a well-characterized St. John's Wort extract (LI-160) in 340 adults with MDD, who all had a baseline total score on the Hamilton Depression Scale of at least 20. Using decreases in HAMD as the primary outcome measure, there were no differences found between a St. John's Wort group vs. placebo vs. sertraline. This study failed to support the efficacy of St. John's Wort in moderately severe depression.² The authors do note that St. John's Wort may be most effective in less severe major depression, but that even this claim can not be supported based on the studies that have been done to date.
  
• A study published in 1999 sought to evaluate the safety and antiretroviral activity of hypericin in HIV-infected subjects. Despite its demonstrated antiretroviral activity both in vitro and in animal models, there was no evidence of antiretroviral activity at this study's completion (based on HIV p34 antigen levels, culture titers, and HIV-RNA levels).⁵
  

Scientific Names | Reported Uses | Scientific Evidence | Adverse Effects | References

Adverse Effects, Contraindications, Drug Interactions:

• In the 1996 meta-analysis performed, authors noted some non-specific gastrointestinal symptoms and allergies in the St. John's Wort groups, but in the placebo-controlled studies, the St. John's Wort extracts were not associated with more adverse events than placebo.⁸
  
• A specific adverse event associated with St. John's Wort is the increase in skin photosensitivity caused in a dose-dependent manner. Indeed, in the aforementioned HIV study, 16 of the 30 study participants had to discontinue treatment before completion of 8 weeks of therapy because of grade 2 or 3 (moderate or severe) phototoxicity.⁵
  
• The safety of concurrent administration of St. John's Wort with prescription or over-the-counter medications has not been studied in depth, and adverse reactions can therefore not be excluded.¹¹
  
• Three cases of possible treatment-emergent mania have been described in the literature in patients with diagnoses of unipolar, bipolar II, and bipolar I disorders after exposure to St. John's Wort.⁹
• Eight case reports exist suggesting that St. John's Wort extract can induce hepatic enzymes (specifically cytochrome p450) potentially lowering therapeutic serum levels of concomitantly taken medications which are metabolized similarly.³
  
• As many drugs used in the perioperative period (such as midazolam, lidocaine, calcium channel blockers, alfentanil) are substrates of p450, it is suggested that patients discontinue the use of St. John's Wort at least 5 days prior to surgery.¹
• Five case studies document symptoms of central serotonin excess (serotonin syndrome) in patients taking both St. John's Wort and a stable dose of an SSRI anti-depressant.⁷

Scientific Names | Reported Uses | Scientific Evidence | Adverse Effects | References

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