Studies of the herbal remedy St. John’s wort have suggested that it may be effective in treating mild to moderate depression—possibly even as effective as prescription antidepressants. Other studies have even suggested it may be effective against moderately severe depression, while still others have found St. John’s wort to be no more effective than a placebo (inactive) pill. Regardless, St. John’s wort is widely used by Americans for relief of depressive symptoms.
The latest research on St. John’s wort, recently published in the
Journal of the American Medical Association,
suggests that St. John’s wort may be no more effective than placebo in treating moderate cases of major depressive disorder. Even more interesting, the popular antidepressant sertraline (Zoloft) also appeared to be no more effective than placebo. What does this mean for the treatment of depression?
Researchers in the Hypericum Depression Trial Study Group enrolled 340 men and women diagnosed with major depressive disorder into an 8-week study. Participants were aged 18 years or older and were recruited from 12 U.S. medical centers between December 1998 and June 2000.
People were excluded from this trial if they showed suicidal or homicidal symptoms in the past year, were pregnant or breast-feeding, had not responded to antidepressants in the past, were currently involved in psychotherapy, or had recently taken sertraline, St. John’s wort or any other compound known to have psychoactive properties. In addition, people with the following medical conditions were excluded: liver disease, seizure disorder, or any mental illness other than major depression.
Participants were randomly assigned to take St. John’s wort, sertraline, or a placebo pill for 8 weeks. Participants taking St. John’s wort all took the Lichtwer extract (LI-160) preparation, which was chosen for its well-known and consistent preparation and because other studies support its potential effectiveness on depression. Doctors were allowed to give participants medication doses within the following parameters, depending on how the participant was responding to treatment:
- St. John’s wort: 900 to 1500 mg per day
- Sertraline: 50 to 100 mg per day
At the start of the study and weekly or biweekly thereafter, participants’ symptoms and progress were assessed by their doctors using all of the following assessment scales:
- Hamilton Depression scale (HAM-D)
- Clinical Global Impressions Scale for severity (CGI-S)
- Clinical Global Impressions Scale for improvement (CGI-I)
At the end of the study, the researchers compared several factors of interest. First they looked at how participants’ HAM-D scores improved over the 8 weeks. Then they compared the change in HAM-D scores across the three treatment groups. Finally, they evaluated whether participants had a “full response” to their medication based on both the HAM-D scores and the CGI scores.
On average, HAM-D scores improved similarly among all three groups, suggesting that the placebo was as effective as both St. John’s wort and sertraline in relieving symptoms of major depression. The same was true for the measure of “full response” to treatment. However, sertraline did appear to be better than placebo and St. John’s wort on the CGI improvement scale scores.
Sertraline and St. John’s wort both produced more adverse side effects than placebo, including nausea, diarrhea, and sweating (sertraline), failure to achieve orgasm (sertraline and St. John’s wort), and frequent urination and swelling (St. John’s wort).
The fact that people taking placebo improved as much as those taking St. John’s wort or sertraline seems to suggest that neither of these remedies are effective in relieving symptoms of major depression. However, it’s important to understand that studies of depression tend to have a high rate of “placebo response,” which makes it very difficult to measure effectiveness of medications and other compounds.
Although these results are interesting, there are some limitations to this study. The therapeutic dose range for sertraline is 50 to 200 mg per day, but this study limited the maximum daily dose to 100 mg. St. John’s wort, on the other hand, was provided up to its maximum dosage. This leaves open the question of whether higher doses of sertraline would have produced more marked results. In addition, there are many others preparations of St. John’s wort on the market that have varying amounts of potentially active ingredients. The effectiveness of these preparations may differ from LI-160.
Does this mean that sertraline and St. John’s wort don’t relieve symptoms of depression? Not necessarily. This study found that these two substances were not better than placebo (which contains no psychoactive substances) in relieving depression. However, the phenomenon of patients responding to a placebo pill is not new. In fact, in trials of antidepressant medications alone, the placebo response can be as high as 35%.
This study adds to a growing body of conflicting reports about the effectiveness of St. John’s wort on depression. It’s important to note that some studies have suggested that St. John’s wort is effective at treating mild to moderate depression. This study, which tested St. John’s wort’s effectiveness in major depression, confirms the findings of another recent study that St. John’s wort is not effective for major depression.
If you suffer from depression or think that you may have depression, tell your health care provider how you are feeling and ask to be referred to a mental health professional. Although St. John’s wort is available without a prescription, it’s not a good idea to self-medicate for depression. There are a number of therapies that may work for you including antidepressant medications, herbal remedies such as St. John’s wort, counseling, and psychotherapy. You need the help of a trained mental health professional to determine which therapy is best for you.
Hypericum Depression Trial Study Group. Effect of
(St. John’s wort) in major depressive disorder: A randomized controlled trial.
Journal of the American Medical Association
. April 10, 2002;287(14):1807-1814.
Kupfer DJ and Frank E. Placebo in Clinical Trials for Depression: Complexity and Necessity.
Journal of the American Medical Association
. April 10, 2002;287(14):1853-1854.
Last reviewed Apr 11, 2002
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