Posted by Larry Hoover on November 25, 2002, at 13:05:21
In reply to Re: St Johns Wort Works!, posted by Bill L on November 25, 2002, at 12:01:17
> Alara - just to be clear, I'm assuming that you are taking 600 mg three times a day for a total of 1800. Is that correct?
>
> Years a go, docs recommended 300 mg 3x per day for a total of 900 mg. Then, a few years a go, people reported more success with double that dosage, or 1800 per day.
>
> When a "big" SJW study was conducted about 2 years a go, the researchers concluded that it was largely ineffective for depression. And that's what the front page headlines on the news and magazines said. But they only used 900 mg and the study only lasted 8 weeks. Many people need more than 8 weeks to get a full effect. My feeling is that the researchers had a vested interest in downplaying the effectiveness of SJW in favor of prescription AD's (where there is a much greater profit margin).Do you think?
I'm employed to criticize scientific studies. It is my opinion that both studies reported in JAMA have significant limitations. I've edited down the abstracts a bit, to make my point.
JAMA 2001 Apr 18;285(15):1978-86
Effectiveness of St John's wort in major depression: a randomized controlled trial.
INTERVENTION: Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n = 102) for 8 weeks.
The number reaching remission of illness was significantly higher with St John's wort than with placebo (P =.02)
CONCLUSION: In this study, St John's wort was not effective for treatment of major depression.
Now, how did they come to ignore the major finding of the study, that there was a significantly higher remission rate with SJW over placebo? They employed a very conservative analytical process called intention-to-treat analysis. I'll spare you the details, but I've never seen such analysis applied to pharmaceutical company antidepressants. Never. (But I don't read them all.....that's my limitation.)
Then, there's this study, which compared SJW to both placebo and sertraline:
JAMA 2002 Apr 10;287(14):1807-14
Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.
INTERVENTIONS: Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. RESULTS: On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum-treated patients (P =.21) and 24.8% of sertraline-treated patients (P =.26).
CONCLUSION: This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.
Pardon me? Notice the complete absence of any mention to the effect that sertraline (Zoloft) failed the experiment? Note any mention of the fact that the SJW product was tested, and shown to contain only a minimum of 0.12% hypericin, rather than the generally accepted minimum of 0.3%? Simple math: 0.12% hypericin times 1500 mg (the highest SJW dose in the trial) equals dosage of 18.0 mg hypericin. Standard dose of 900 mg of 0.30% hypericin gives dosage of 27.0 mg hypericin. And that's the recommended dose for mild to moderate depression, not the serious depression experienced by these subjects.
It is standard medical practice to give an antidepressant a full trial before withdrawing it. You gradually ramp up the dose until one of two things occurs: a) remission of symptoms; b) intolerable side-effects. The same thing goes for SJW; dose should be adjusted to symptoms. There has never been a reported case of SJW overdose in the literature (that I've ever seen, anyway, and I look). There is no reason to restrict SJW dosage to that given for mild to moderate depression if one is attempting to treat serious depression.
What is amazing, to my mind, is that these two studies didn't get the same press.
Can Fam Physician 2002 May;48:905-12
St John's wort or sertraline? Randomized controlled trial in primary care.
van Gurp G, Meterissian GB, Haiek LN, McCusker J, Bellavance F.
Emergency Department, St Mary's Hospital Centre, 3830 Lacombe Ave, Montreal, QC. [email protected]
OBJECTIVE: To compare the change in severity of depressive symptoms and occurrence of side effects in primary care patients treated with St John's wort (SJW) and sertraline. DESIGN: Double-blind, randomized 12-week trial. SETTING: Community-based offices of 12 family physicians practising in greater Montreal, Que. PARTICIPANTS: Eighty-seven men and women with major depression and an initial score of > or = 16 on the Hamilton Rating Scale for Depression (Ham-D). INTERVENTIONS: Patients were randomized to treatment with either sertraline (50 to 100 mg/d) or SJW (900 to 1800 mg/d) in a double-blind fashion. Assessment of depression was done at entry and at 2, 4, 8, and 12 weeks using the Ham-D, the Beck Depression Inventory (BDI), and a questionnaire asking about compliance and side effects. MAIN OUTCOME MEASURES: Changes from baseline in Ham-D and BDI scores and self-reported side effects. RESULTS: There were no important differences in changes in mean Ham-D and BDI scores (using intention-to-treat analysis), with and without adjustment for baseline demographic characteristics, between the two groups at 12 weeks. Significantly more side effects were reported in the sertraline group than in the SJW group at 2 and 4 weeks' follow up. CONCLUSION: The more benign side effects of SJW make it a good first choice for this patient population.
Here's one about severely depressed subjects successfully treated with SJW:
Pharmacopsychiatry 1997 Sep;30 Suppl 2:81-5
Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10.
Vorbach EU, Arnoldt KH, Hubner WD.
Department of Psychiatry and Psychotherapy, Ev. Krankenhaus Elisabethenstift, Darmstadt, Germany.
The special extract of St. John's wort, LI 160, exhibited a superior antidepressant efficacy compared to placebo in several controlled trials. Two further trials demonstrated a similar reduction of depressive symptomatology under LI 160 compared to tricyclics. All these trials were performed in mildly to moderately depressed patients. The present investigation was a randomized, controlled, multicentre, 6-week trial comparing 1800 mg LI 160/die to 150 mg imipramine/die in severely depressed patients according to ICD-10. The main efficacy parameter, a reduction of the total score of the Hamilton Depression Scale, proved both treatment regimens very effective at the end of the 6 week treatment period (mean values 25.3 to 14.5 in the LI 160 group and 26.1 to 13.6 in the imipramine group), but not statistically equivalent within a a-priori defined 25% interval of deviation. The analysis of subgroups with more than a 33% and 50% reduction of the HAMD total score justified the assumption of equivalence within a 25% deviation interval. This view was also supported by the global efficacy ratings from patients and investigators. Regarding adverse events, the nonrejection of the nonequivalence hypothesis denotes a superiority of the herbal antidepressant. These main result indicate that LI 160 might be a treatment alternative to the synthetic tricyclic antidepressant imipramine in the majority of severe forms of depressions. However, more studies of this type must be performed before a stronger recommendation can be made.
Tricyclics like imipramine are often recommended for the most severe forms of depression because they work. It's the side effect profile that limits them (anticholinergic effects, praticularly).
IMHO, there are two major problems with people trying SJW and getting no response. One is the rampant fraud in the herbal industry. Because the herbal supplement suppliers are not bound by legislation which requires them to assure the contents of their supplements actually contains what the label says, you don't know what you're buying. Independent analyses of commercial SJW products show that up to 1/3 of all products contain no or negligible amounts of the active ingredients, 1/3 contain substantial amounts, but appreciably less than the label states, and 1/3 meet (or exceed) the label amounts. I want to ask you, what major industrial concern stands to profit from this state of affairs? Pharmaceutical companies. Destroy peoples' confidence in herbal products, and they're the only players. Germany was able to quickly and efficiently bring in pharmaceutical-type standards for herbal products. Surely America can do the same.
The second issue, as I mentioned, is that people seldom give the same sort of trial for SJW that they give for a prescribed med, i.e. increase the dose until either remission or side-effects occur.
I'm skeptical of the JAMA reports. And I think, for good reason.
Lar
poster:Larry Hoover
thread:128819
URL: http://www.dr-bob.org/babble/20021122/msgs/129227.html