Is St. John’s Wort Effective for Major Depression?

Healthnotes Newswire (August 10, 2006)—St. John’s wort extract is the best-known herbal treatment for mild to moderate depression—but can it be used to treat major depression as well? If so, how much is needed? A new clinical trial, published in the journal BMC Medicine, attempted to answer these questions.

“St. John’s wort [Hypericum perforatum] is an attractive treatment option for patients with mild to moderately severe depression because it has been shown in clinical trials to be effective and well tolerated with a more favorable side effect profile than many [prescription] antidepressants,” said Siegfried Kasper, MD, professor and chairman of the Department of Medical Psychiatry at Vienna Medical University, and lead author of the study. “For patients with major depression, however, [the use of St. John’s wort] remains somewhat controversial since some studies in major depression showed no significant effect.”

Dr. Kaspar and colleagues enrolled 332 volunteers with major depressive episodes in his study. They were randomly assigned to receive 600 mg once per day of St. John’s wort extract, 600 mg twice per day (1,200 mg per day) of the same extract, or a placebo for six weeks.

Both groups taking St. John’s wort extract experienced significantly greater relief than those taking placebo. The effects of 600 mg once per day were greater than those found in a previous placebo-controlled study of major depression, in which participants took 300 mg three times a day. There was no significant difference between the effects of 600 mg per day and 1,200 mg per day of St. John’s wort.

Major depression (also known as major depressive episodes) can be mild, moderate, or severe, but differs from the “mild to moderate depression” described in most studies of St. John’s wort. Mild to moderate depression refers to depressive symptoms discovered by using one or several standardized rating scales. These scales do not necessarily match the American Psychiatric Association’s official criteria for major depression, as described in their Diagnostic and Statistical Manual of Mental Disorders.

To have an official diagnosis of major depression, a person must have five or more of the following symptoms during the same two-week period, and they must represent a change in behavior:

(1) Depressed mood or loss of interest or pleasure, most of the day, nearly every day (this must be at least one of the symptoms; the others would include four or more of the following)

(2) Significant weight loss when not dieting or weight gain (for example, a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day

(3) Insomnia or too much sleep (hypersomnia) nearly every day

(4) Agitation or slowing of voluntary body movements nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)

(5) Fatigue or loss of energy nearly every day

(6) Feelings of worthlessness or excessive or inappropriate guilt nearly every day

(7) Diminished ability to think or concentrate, or indecisiveness, nearly every day

(8) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

These symptoms cause significant distress or impairment in social, occupational, or other important areas of functioning, and the are not due to the direct effects of a substance (for example, an abused drug, a medication) or a general medical condition (for example, hypothyroidism).

In the new study, mild adverse effects were seen in both of the St. John’s wort groups (approximately 24% of the people taking St. John’s wort extract, compared with approximately 16% in the placebo group). The most commonly reported problem was gastrointestinal upset. Sensitivity to light and menstrual complications were also reported. These adverse reactions have been noted previously for St. John’s wort, and they are usually transient and infrequent.

“The results of this study demonstrate the superior antidepressant efficacy of [St. John’s wort extract] compared to placebo in the treatment of patients with a mild or moderate major depressive episode after six weeks of treatment,” the study concluded. “Although the [St. John’s wort extract] 1,200 mg per day dose did not prove to be significantly more effective than the 600 mg per day dose, the doubled dose was equally safe and well tolerated.”

It should be noted that two of the authors are employees of the pharmaceutical company that manufactured the St. John’s wort extract used in the study. The other three authors received consultancy fees from that company.

Jeremy Appleton, ND, CNS, is a licensed naturopathic physician, certified nutrition specialist, and published author. Dr. Appleton was the Nutrition Department Chair at the National College of Naturopathic Medicine, has served on the faculty at Bastyr University of Natural Health Sciences, and is a former Healthnotes Senior Science Editor and a founding contributor to Healthnotes Newswire. He has worked extensively in scientific and regulatory affairs in the supplement industry and is now a consultant through his company Praxis Natural Products Consulting and Wellness Services.

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