St. John's Wort
(Hypericum perforatum)

St. John's wort (Hypericum perforatum) Monograph
Alternative Medicine Review 2004 (Sep); 9 (3): 318–325 ~ FULL TEXT
A meta-analysis published in 1996 of 23 studies involving over 1,500 individuals found significantly positive responses to St. John’s wort based on analysis of the Hamilton Depression Scale (HAMD) before and after treatment. [19] This was supported by a more recent meta-analysis covering clinical trials published through 2000. [20] In 2000, the Annals of Internal Medicine featured a two-part overview and critique of newer drug therapies for depression and dysthymia (a chronic but milder form of depression), and included St. John’s wort as a potential treatment for both conditions. [21, 22] Both reviews conclude St. John’s wort is more effective than placebo for the treatment of mild-to-moderate depression and less likely to cause side effects than commonly prescribed antidepressants. The 2000 meta-analysis of St. John’s wort clinical trials lists 16 placebo-controlled trials on persons with mild-to-moderate depression. [20]

Experience with St John's Wort (Hypericum perforatum) in Children
Under 12 Years with Symptoms of Depression and Psychovegetative Disturbances
Phytother Res 2001 (Jun); 15 (4): 367–370
The value of an extract of Hypericum perforatum (St John's wort) for children with mild to moderate depressive symptoms was investigated for the first time in a multi-centre post-marketing surveillance study. Based on the data available for analysis, the number of physicians rating effectiveness as 'good' or 'excellent' was 72% after 2 weeks, 97% after 4 weeks and 100% after 6 weeks. The ratings by parents were very similar.

Comparison of St John's wort and Imipramine for Treating Depression:
Randomised Controlled Trial
British Medical Journal 2000 (Sep 2); 321 (7260): 536–539
This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better.

Hypericum Extract Versus Imipramine or Placebo in Patients with
Moderate Depression: Randomised Multicentre Study of
Treatment for Eight Weeks
British Medical Journal 1999 (Dec 11); 319 (7224): 534–1538
At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.

St. John's wort (Hypericum perforatum) Monograph
Alternative Medicine Review 1999 (Jun);   4 (3):   190–192 ~ FULL TEXT
While it is not yet known definitively which constituent or constituents are responsible for Hypericum's anti-depressant effects, recent studies seem to indicate the compound hyperforin is at least in part responsible. Researchers found the concentration of this compound to significantly contribute, in a dose-dependent manner, to the anti-depressant effect of St. John's wort. [1] Another study, utilizing two behavioral assessments typically used to assess anti-depressant effects, found a positive correlation between hyperforin concentration and anti-depressant efficacy. The concentration of other constituents of several hypericum extracts were not found to be connected to their efficacy. [2]

St. John's wort (Hypericum perforatum): Clinical Effects
on Depression and Other Conditions
Alternative Medicine Review 1998 (Feb); 3 (1): 18–26 ~ FULL TEXT
Hypericum has been favorably compared to numerous antidepressant drugs, the studies having revealed equivalent results and a much more favorable incidence of side effects. Studies have also demonstrated its efficacy in treating seasonal affective disorder.

LI 160, An Extract of St. John's wort, Versus Amitriptyline in
Mildly to Moderately Depressed Outpatients:
A Controlled 6-week Clinical Trial
Pharmacopsychiatry 1997 (Sep); 30 Suppl 27: 77–80
With regard to tolerability, LI 160 was clearly superior to amitriptyline, particularly in relation to anticholinergic and Central Nervous System adverse events. Thus, 37% of the LI 160 treated patients reported adverse events, compared to 64% in the amitriptyline group. This considerable superiority in tolerability for LI 160 in relation to amitriptyline, could confer an advantage in improving compliance for antidepressant pharmacotherapy.

Effects of Hypericum Extract (LI 160) in Biochemical Models
of Antidepressant Activity
Pharmacopsychiatry 1997 (Sep); 30 Suppl 2: 102–107 Moreover, subchronic treatment of rats with hypericum extract led to a significant down-regulation of beta-receptors and to a significant up-regulation of 5-HT2-receptors in the frontal cortex. The data might suggest that hypericum extract acts via similar biochemical mechanisms to other antidepressants (e.g. tricyclics).

St John's wort for Depression: An Overview and Meta-analysis
of Randomised Clinical Trials
British Medical Journal 1996 (Aug 3); 313 (7052): 253–258
There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed.