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Rapaport 2011 Treatment of minor depression with St. John's Wort or citalopram: Failure to show benefit over placebo


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It looks like this study was trying to show citalopram (Celexa) was superior to St. John's Wort in "minor" depression; instead, it found they were both worthless and generated unpleasant side effects. NIMH concluded: "The results of this study, consistent with earlier research, do not in support the use of medications for mild depression."


J Psychiatr Res. 2011 Jul;45(7):931-41. Epub 2011 May 31.

The treatment of minor depression with St. John's Wort or citalopram: Failure to show benefit over placebo.


Rapaport MH, Nierenberg AA, Howland R, Dording C, Schettler PJ, Mischoulon D.



Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, USA.


Abstract at http://www.ncbi.nlm.nih.gov/pubmed/21632064


This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John's Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John's Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John's Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated.





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

NIMH Science Update • July 22, 2011


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 in 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.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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