St. John's Wort

Authors:

Andrew Bartlow, Jay Shah, Justin Crawford, Kenneth M. Klemow, Michael Ritsick, Neil Kocher

Findings:

St. John's Wort (SJW) has a long history of use and is extensively studied for depression, showing efficacy particularly for mild to moderate forms, with recent Cochrane Reviews also pointing to efficacy in major depression, though some conflicting results exist. Research also supports its use for cancer, inflammation, bacterial/viral diseases, and as an antioxidant/neuroprotective agent, with hyperforin and hypericin being key active compounds. While SJW preparations generally have few adverse effects at recommended doses, they cause numerous drug interactions by inducing enzymes like P-glycoprotein and cytochrome P450s (e.g., CYP3A4), primarily through hyperforin.

Participants:

The text reviews studies conducted on isolated tissue samples, animal models (e.g., rats, mice as mentioned in sections like 11.6.1.1, 11.6.2, 11.6.4, 11.6.5, 11.6.7), and human clinical trials. Human participants mentioned in the reviewed literature include adult outpatients with major depression (e.g., N=200 in Shelton et al. 2001; N=340 in Hypericum Depression Trial Study Group 2002), patients in meta-analyses (e.g., 2291 to 5489 patients across various trials cited by Linde et al.), HIV-infected patients (N=30 in Gulick et al. 1999), patients with skin conditions (Kacerovská et al. 2008), and healthy subjects/volunteers in pharmacokinetic studies (e.g., N=8 to N=16 in various drug interaction studies cited in section 11.7.2.3).

Dosage:

Clinical trials using various H. perforatum preparations report typical dosages in the range of 300-1800 mg/day of standardized extract. Specific commercial preparations mentioned include LI 160 (standardized to 0.3% hypericin, 300mg capsules), Ze 117 (dosage 500 mg/day, 0.2% hyperforin), WS 5570 (300 or 600 mg tablets, 5-6% hyperforin, 0.12-0.28% hypericin), and STEI 300 (350mg capsules, 0.2-0.3% hypericin, 2-3% hyperforin). The German Commission E and European Scientific Cooperative on Phytotherapy (ESCOP) monographs recommend 900 mg of standardized extract per day. High doses of hypericin (e.g., 0.5 mg/kg of body weight for AIDS treatments) were associated with phototoxicity. Drug interaction studies often involve multi-day treatments (e.g., 10-15 days) with SJW.

Study Quality Assessment:

The text is a chapter reviewing literature on St. John's Wort from the past 30 years, referencing studies including in vitro analyses ('isolated tissue samples'), animal model experiments, and human clinical trials. It states that the effectiveness for depression is 'particularly well studied' and underlying mechanisms 'well understood'. Specific study designs cited from the reviewed literature include 'randomized', 'double-blind', 'placebo-controlled', and 'three-armed' trials, as well as 'meta-analyses' and 'Cochrane Reviews'. The text notes critiques of some studies (e.g., 'unrealistically low' dosages of comparators, 'short duration') and discusses conflicting results (e.g., U.S. vs. German depression studies, 'unusually high placebo response'). It highlights that benefits are often linked to 'standardized extracts' (e.g., LI 160, WS 5570/2, ZE 117) and points out needs for further research, including replicability for some drug interaction findings.

All Effects:

Authors:

Hubner W-D, Kirste T

Participants:

children under 12 years with symptoms of depression and psychovegetative disturbances

Authors:

Hypericum Depression Trial Study Group

Findings:

On the 2 primary outcome measures (change in HAM-D total score and rates of full response), neither sertraline nor Hypericum perforatum was significantly different from placebo after 8 weeks. The study fails to support the efficacy of H perforatum in moderately severe major depression.

Participants:

Adult outpatients (n = 340) with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20.

Dosage:

Daily dose of H perforatum could range from 900 to 1500 mg; sertraline from 50 to 100 mg, based on clinical response.

Study Quality Assessment:

Double-blind, randomized, placebo-controlled trial. N=340. Active comparator: sertraline. Duration: 8 weeks, with responders continuing blinded treatment for another 18 weeks. Main outcome measures: Change in HAM-D total score, rates of full response (HAM-D and CGI scores). Limitation mentioned: 'low assay sensitivity of the trial'.

All Effects:

Findings:

Many studies have proved the efficacy of some St. John's wort extracts in mild to moderate depression.

Study Quality Assessment:

Mentions 'many studies have proved the efficacy'