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Glenn Yank, MD is a Psychiatrist located in Tennessee.


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Question:
With depression and Bi-polar issues, I would like to find information on natural products (herbal) if possible. I do not like the fact of using drugs that so far have not been effective and just merely sedate. Thanks. Janice L. A Concerned Parent In A War Against Legal Drugs

Answer:

Although I would agree with you that there is little benefit to continuing to take a drug that is not effective and merely sedates you, unfortunately there is no evidence that any herbal products are effective in bipolar disorder. St. John’s wort is likely effective in mild unipolar depression (no history of mania or hypomania) as will be discussed below. However there are case reports of St. John’s wort causing mania in bipolar patients (which antidepressants are known to do). I could argue that lithium is a natural product, since it is processed only by refining naturally occurring salts, and is not a complex molecule synthesized in a laboratory. Lithium remains an extremely effective medicine for bipolar depression (depression in a person with a history of previous manic or hypomanic episodes). A newer and non-sedating alternative for bipolar depression is the anticonvulsant Lamictal (lamotrigine). Studies by NIMH have shown this drug to be particularly effective for depression in patients with bipolar illness, unlikely to cause manic swings, and less sedating than placebo (meaning it is usually a little activating). Lamictal is certainly not a “natural” product, and is not without side effects, rashes being the most common, but it has certainly helped a lot of my patients with depression and bipolar symptoms.

With regard to St. John’s wort and depression, I have included the following information from a recent, comprehensive review article. The bottom line is that St. John’s wort is probably helpful in mild, unipolar depression. There is better data, in my opinion, for cognitive behavior therapy for this condition, and that has no drug side effects. But, for those who may be considering St. John’s wort, I hope you find this useful:

Current St. John’s wort research from mode of action to clinical efficacy; Walter E. Müller; Pharmacological Research Volume 47, Issue 2 , February 2003, Pages 101-109

“Although the therapeutic use of St. John’s wort extracts first came from practice, the high acceptance, such as found today in Germany and a few other countries, can only be explained by the fact that over the past years a number of good clinical studies have been carried out which confirm the efficacy and tolerability of St. John’s wort extracts in mild depressive disorders.

The therapeutic efficacy has recently been questioned by an American study. The essential finding of this study revealed no difference in time course of the HAMD (Hamilton Depression Scale) primary target criterion over the 8 weeks, as the placebo and St. John’s wort curves did not differ significantly. This also applied to the majority of other scales investigated. However, if the proportional distribution of responders (50% or higher improvement at end point) is considered, a numerical advantage of St. John’s wort extract compared to placebo was found, although not of statistical significance. In general, placebo response (14%) was exceptionally low. The situation was different for the rate of remission (HAMD values <7 at the end of the study, i.e. symptom-free patients), where almost three-fold more remissions were observed under St. John’s wort extract than under placebo. This difference was statistically significant.

This study is indeed a negative study (primary target criterion HAMD), but remains not without some evidence for the efficacy of St. John’s wort. Nevertheless, the study is in marked contrast to almost all other clinical studies, as well as the study discussed below.

Extremely sick patients with a mean duration of depressive illness of about 10 years were included in this study by Shelton et al. The acute depressive phase treated in the study with St. John’s wort or placebo lasted 2 years on average, which is also extremely long for such a study. Over 40% of the patients were additionally characterized as the melancholic sub-type, which is also indicative of severe depression. The inclusion of severely and chronically ill depressive patients is in marked contrast to the clinical use and the registered indications of St. John’s wort extracts in Germany, where only mild to moderate depression is addressed. Many physicians who willingly and frequently prescribe St. John’s wort extracts would not have prescribed them for the patients included in the Shelton study.

To sum up: certainly an interesting study, where the central statement, that St. John’s wort extracts in the dose used (usually 900 mg per day) is possibly not sufficiently effective for severely and chronically depressive patients, should be accepted. Apart from this, it is known that St. John’s wort extract is not the therapy of choice in cases of severe depressive illness. Most important, the indirect implication of this study that other antidepressant (e.g. SSRIs) would have been more effective is not confirmed. Even more, a most recent American study, where even slightly less severely and chronically ill depressant patients were included, failed to show therapeutic efficacy not only for St. John’s wort but also for the active comparator sertraline (Zoloft, an SSRI). This shows, that patient selection in both studies was not only biased against the herbal but also against one of the mostly prescribed synthetic antidepressant as well.

A recently published placebo-controlled, double-blind study carried out in France by Lecrubier et al. was of similar design. There was a very clear placebo response, however, and a significant superiority of the St. John’s wort extract according to the HAMD scale at the end point of the study. The placebo response at the end of the 6-week therapy phase of over 40% is therefore strikingly different to the placebo response of 17% in the Shelton study. Additional analyses in the Lecrubier study with the sub-scale melancholia and the sub-scale anxiety and somatization showed highly significant benefits of St. John’s wort extract treatment in both domains. The Lecrubier study is therefore in agreement both with many other clinical studies on antidepressants, and with a series of other recently published placebo-controlled clinical studies on St. John’s wort extract of high methodological standard. It emphasizes once again the exceptional position of the two American studies.

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