There are at least 16 randomized, double-blind studies comparing the antidepressant effect of hypericum extracts to Placebos. There is also one comparing with placebo light therapy.
In thirteen of the studies there was a statistically significant difference in efficacy similar to the difference shown between effects of synthetic antidepressants compared to placebos.
Two of these studies were judged as of low quality (collecting only 25 points out of 110) in terms of reliability concerning methods, patient material and statistical analysis in the systematic, criteria-based review by Ernst. The third one is from a thesis, not yet published in a medical magazine. The study by Osterheider managed to accomplish 0% treatment responses in both placebo and treatment group, a very unusual result. According to informal sources one reason for this very unusual result might have been that a person unknown to the patients did the ratings of depressive symptoms etc., and not their normal doctor. This was not popular among the patients and might have influenced the response rate. In the study by König there were extremely many side-effects, 26% on placebo! There were also many treatment dropouts (25%)
In no one of the studies here has been any significant difference in terms of ADRs between hypericum and placebo. In a summary of 15 of these studies performed on 1008 patients there was no difference concerning amount of side-effects (4.1% on hypericum and 4.8% on placebo), and actually less treatment dropouts because of side effects among patients treated with hypericum (0.4% versus 1.6%). One can therefore say that hypericum seems to have no significant side effects at all, except for allergic reactions.
Hypericum has also been proven effective in the treatment of secondary symptoms of depression like headache, sweating, heart palpitations, anxiety and insomnia. There are also promising results in treatment of anxiety syndrome.