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For Minor Depression, Study Shows No Benefit Over Placebo from St. John’s Wort, Citalopram

Science Update

yellow flower

An extract of the herb St. John's Wort and a standard antidepressant medication both failed to outdo a placebo in relieving symptoms of minor depression in a clinical trial comparing the three. The results of this study, consistent with earlier research, do not support the use of medications for mild depression.


St. John's Wort  is a plant whose yellow flowers have been the source of extracts used medicinally for centuries. It is widely used to treat depression, as a nutritional supplement in the United States, and as a prescription medication in Europe. Evidence from clinical trials of St. John's Wort has failed to show effectiveness for treatment of major depression; but research has raised the question as to whether the herb might offer benefit for people with less severe depression.

This Study

This study, focusing specifically on minor depression, was conducted by Mark Hyman Rapaport and colleagues at the Cedars-Sinai Medical Center and David Geffen School of Medicine in Los Angeles; the Massachusetts General Hospital, in Boston; and the University of Pittsburgh. Participants in the study had minor depression, defined as the presence of two to four symptoms used to diagnose major depression, with at least one symptom being depressed mood or anhedonia, a lack of pleasure in activities usually found enjoyable. Symptoms had to have been present for six months to two years. Subjects were randomly assigned to receive St. John's Wort, the antidepressant medication citalopram, or a placebo. Neither participants, nor the staff treating them, knew what treatment they took. Seventy-three subjects completed the trial.

Results from the trial showed that no treatment relieved depression more than any other; patients in all three of the treatment groups showed improvements in symptoms over the course of the study, and in measures of quality of life and psychological well-being.

Patients in all three treatment groups—including placebo—also frequently reported side effects. In addition, before treatment began in this study, more than half of participants responded positively when they were asked if they had any of a broad list of physical or psychological complaints. This finding suggests that it's important to assess both physical and psychological symptoms even before treatment begins; otherwise, many of these symptoms might be interpreted as medication-related.


While minor depression is by definition a milder condition than major depression, research suggests it has consequences for health and well-being that go beyond the symptoms themselves, including lost work days, social difficulties, and possibly a higher risk of developing future major depression.

The authors are careful to point out that the reason that there was no difference in benefit between St. John's Wort, citalopram, and placebo was not because the study was too small to detect a difference, but because participants taking placebo experienced substantial improvement in measures of depression and well-being—participation in the study had positive effects. In addition, participants taking all three treatments—even those on placebo—experienced side-effects. Fewer of the subjects taking St. John's Wort reported that side effects were distressing (40 vs. 60 percent); but St. John's Wort recipients reported more gastrointestinal and sleep problems than those receiving placebo.

Identifying effective and safe ways to treat minor depression remains an important goal; further research on non-pharmacologic treatment is needed to identify the optimal psychotherapies for minor depression.

This study was funded by the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine, National Institutes of Health.


Rapaport, M.H., Nierenberg, A.A., Howland, R., Dording, C., Schettler, P.J., and Mischoulon, D. The treatment of minor depression with St. John's Wort or citalopram: Failure to show benefit over placebo. Journal of Psychiatric Research 45:931-941, 2011.