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National Institutes of Health

Press Release
March 21, 2003

Treatment for Minor Depression

In a new approach to research on minor depression, the National Institutes of Health (NIH) has launched a four-year study to determine the safety and effectiveness of St. John's wort, a common herbal supplement, and citalopram, a standard antidepressant, compared to placebo.

The trial is being conducted at three sites. A total of 300 participants with minor depression will be randomly assigned a standardized extract of St. John's wort (Hypericum perforatum), citalopram, or placebo in a 12-week double-blind trial. Researchers will assess changes in patients' symptoms, functioning, and quality of life. Those who show no improvement will receive the active treatment they hadn't been assigned before, while patients with improved symptoms will take their assigned treatment for another 14 weeks for a total of 26 weeks.

The more than $4 million collaborative study is funded by the National Institute of Mental Health (NIMH), the National Center for Complementary and Alternative Medicine (NCCAM), and the Office of Dietary Supplements (ODS).

Minor depression is a common disorder that may impair a person's functioning and quality of life and is a serious risk factor for major depression. Yet it is underdiagnosed and undertreated. The study addresses a need for definitive data on therapy for this significant health problem. Patients with minor depression who seek treatment from family doctors are often treated with prescription antidepressants, if their mood disorder is diagnosed at all. Many people use St. John's wort without consulting a physician. This study will help determine how the herbal agent and the antidepressant fit in the overall management of the disorder.

"If the trial demonstrates that citalopram or St. John's wort benefits patients with minor depression, it will expand our understanding of this underrecognized mood disorder and offer new evidence-based treatment recommendations for either primary care or mental health clinicians," explained Matthew Rudorfer, M.D., Associate Director of Treatment Research, Division of Services and Intervention Research, NIMH.

"There is high public interest in herbal remedies for depression," according to Stephen E. Straus, M.D., NCCAM Director. "Our intent is to study St. John's wort for the spectrum of depressive conditions for which the public considers its use. This new study extends our earlier research efforts from the more serious form of depression to a clinically less serious one, yet one that is, in fact, of considerable public health significance," he said.

Men and women age 18 to 85 who meet diagnostic criteria for minor depression are eligible to participate. They must have experienced depressive symptoms for at least 6 months but less than 2 years continuously without meeting criteria for a major depressive episode or dysthymia within the past year. Additional exclusionary criteria include other mental disorders, such as schizophrenia, bipolar disorder, anxiety, and substance use disorders. Individuals with some active physical illnesses, such as cardiovascular, renal, respiratory, endocrine, neurological, or blood diseases also are not eligible for the study.

Participants are interviewed at an initial screening visit, during the initial 2-week period when they are withdrawn from all psychotropic medications, at baseline, and every 2 weeks thereafter during the study. At the screening visit, Week 12, and Week 20, patients will undergo a complete blood count with laboratory tests. Well validated scales will be used to assess symptoms, dysfunction, and well-being.

Minor depression affects about 7.5 percent of Americans during their lifetime. Although there is broad knowledge about the scope of suffering and disability due to major depressive disorder, less is known about the day-to-day struggles faced by people with minor depression. Its symptoms are the same as those of major depression, though fewer in number and causing less impairment. They include:

Trials are being conducted in:

Boston, Massachusetts, at Massachusetts General Hospital. Andrew A. Nierenberg, M.D., is the principal investigator. The coordinator is Megan Hughes at 617-726-3129;

Los Angeles, California, at Cedars-Sinai Medical Center. Mark Rapaport, M.D., is the principal investigator. The coordinator is Justin Henderson at 310-423-0744;

Pittsburgh, Pennsylvania, at the University of Pittsburgh. Robert Howland, M.D., is the principal investigator. The coordinator is Michael Lightfoot at 412-624-5035;

For more information about the study go to, For press calls at NIMH, 301-443-4536; NCCAM, 301-496-7790; and ODS, 301-496-4819.

NIMH, NCCAM, and ODS are part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.


The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.