has anyone tried St. John's wort for depression?

Hi,
I have been resisting standard anti-depressants because I get some nasty side effects. Has anyone tried St. John's Wort? I just started it, and am hoping I can do better with it and avoid spiralling down into the depression I can feel coming on - anyone tried it?

Pretty safe as long as you are on nothing else. It is basically an MAOI so do some reserch on that and you will have a good idea....

It is important to try and get quality controlled capsules too so that they have enough of each active ingredient in each capsule. Something that can go wrong with St John's Wort (I've heard) is that there are some brands that don't have consistency in active ingredient across tablets and / or they contain less of the active ingredient than they say they do.

I've heard the laws are stricter in Canada than the US regarding quality control on these kinds of non prescription products. Might be worth looking into that online too.

And looking at how hefty of a dosage you should be looking at taking (sometimes people are surprised at how much is reccomended to take for people who are really rather depressed rather than people who are just feeling a 'little flat')

psisci - FYI. The 1984 study by Suzuki, Katsumata, etal, in the journal Planta Medica (1884; 50: 272-274) reported that hypericin in SJW had significant mono-amine oxidase activity, but subsequent studies suggested that impurities in the hypericin were responsible for the results. Further investigations did show that SJW did have minimal MAOI activity, but at levels far below that required for therapeutic effect (see: Upton R, editor. St. John's Wort Monograph. Santa Cruz. American Herbal Pharmacopoeia Inc., 1997: 1-32). Inhibition of serotonin reuptake activity has been suggested, but again concentrations appear to be inadequate (see Upton, 1997). Indications are that the psychotherapeutic properties of hypericum (another constituent of SJW) are due to other causes, possibly related to GABA or reduced interleukin-6 expression (see Upton, 1997), but further studies are needed.

Studies of hyperforin was identified as a major active component of hypericum extract, and is a potent inhibitor of serotonin, norepinephrine, and dopamine neuronal reuptake. Hyperforin also inhibits the synaptosomal uptake of L-glutamate and stimulates GABA receptors (see Chatterjee SS, et al. Life Sci 63; 1998: 499-510a).

That being said, the actual mechanism of action of SJW has not been definitively established. Compared to SSRIs, TCAs, and SNRIs, SJW has far less antidepressant activity, but not a more favourable side effects profile, and can interact adversely with several medications due to inhibition of the liver's Cytochrome P-450 system. SJW also can cause photosensitivty reactions, making one's skin more sensitive to sunlight.

Also, all positive clinical trials of SJW use the expensive plant extracts, which can put a good dent in one's pocketbook.

Just my two-bits. - Cam

A very quick google scholar search revealed this:

Titre du document / Document title
St John's wort for depression: A systematic review
Auteur(s) / Author(s)
GASTER B. (1) ; HOLROYD J. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Medicine, University of Washington, Seattle, ETATS-UNIS

Résumé / Abstract
To address whether St John's wort is useful for the treatment of depression we attempted to retrieve all English-language articles with data on the efficacy, safety, and availability of St John's wort. Randomized, controlled, double-blind trials were selected and assessed for methodological quality using a standardized checklist, and data on pharmacology, cost, regulation, and safety were extracted. Eight studies were identified, found to be of generally good methodological quality, and determined to provide a modest amount of data to suggest that St John's wort is more effective than placebo in the treatment of mild to moderate depression. The absolute increased response rate with the use of St John's wort ranged from 23% to 55% higher than with placebo, but ranged from 6% to 18% lower compared with tricyclic antidepressants. More data are required to assess both its use in severe depression and its efficacy compared with other antidepressants. Rates of side effects were low. As a dietary supplement, St John's wort is currently largely unregulated, but the Food and Drug Administration is reviewing plans to tighten its regulatory oversight.
Revue / Journal Title
Archives of internal medicine (Arch. intern. med.) ISSN 0003-9926 CODEN AIMDAP
Source / Source
2000, vol. 160, no2, pp. 152-156 (40 ref.)

That was in 2000. I don't know what research has been done since then...

So...

I guess the question is...

Who is sponsoring you? Lilly?

;-)

alexandra - Janssen Pharmaceuticals provide better meals ; alas, they don't have an antidepressant.

BMJ and NEJM both have published recent studies concluding that SJW isn't much better than placebo (ie. SJW is not worth the money). Hey, if it were any good, I'd say so. Besides, antidepressants are only tools for psychotherapy. No antidepressant is a cure, you have to fix the problem that caused the depression in the first place, and that takes understanding and hard work, usually with a therapist.

- Cam

And here is another (more recent but also more favourable with respect to st johns wort compared with standard anti-depressants):

Rajanikanth Madabushi1, Bruno Frank2, Bernd Drewelow3, Hartmut Derendorf1 and Veronika Butterweck1

(1) Department of Pharmaceutics, College of Pharmacy, University of Florida, P.O. 100494, Gainesville, FL 32610, USA
(2) Kneipp Werke Würzburg, Germany, Würzburg
(3) Institute of Clinical Pharmacology, University of Rostock, Germany, Rostock

Received: 16 September 2005 Accepted: 6 January 2006 Published online: 14 February 2006

Abstract Recently, interactions of herbal medicines with synthetic drugs came into focus of particular interest. In the past 3 years, more than 50 papers were published regarding interactions between St. John’s wort (Hypericum perforatum L.; SJW) and prescription drugs. Co-medication with SJW resulted in decreased plasma concentrations of a number of drugs including amitriptyline, cyclosporine, digoxin, indinavir, irinotecan, warfarin, phenprocoumon, alprazolam, dextrometorphane, simvastatin, and oral contraceptives. Sufficient evidence from interaction studies and case reports indicate that SJW is a potent inducer of cytochrome P450 enzymes (particularly CYP3A4) and/or P-glycoprotein. Recent studies could show that the degree of enzyme induction by SJW correlates strongly with the amount of hyperforin found in the product. Products that do not contain substantial amounts of hyperforin (<1%) have not been shown to produce clinically relevant enzyme induction. On the other hand, some evidence suggests that hyperforin may also contribute to the antidepressant activity of SJW. However, clinical studies using SJW preparations with a low hyperforin amount (<1%) clearly demonstrated the superiority of this plant extract over placebo and its equivalence to imipramine and fluoxetine in the treatment of mild to moderate forms of depression. In the present paper clinical significant SJW interactions are critically evaluated against the background of hyperforin.

The birth control thing is something to keep in mind if it applies (antibiotics similarly reduce the efficacy of birth control pills). It is important to tell your doctor / pharmacist that you are taking st john's wort so they can figure possible interactions with what they are planning on prescribing you.

With respect to the mild / moderate thing... What counts as (clinically) severe these days? Constant suicidal ideation / suicidal attempts and / or catatonia???

> BMJ and NEJM both have published recent studies concluding that SJW isn't much better than placebo

do you have a reference?

alexandra - My apologies; I haven't personally researched SJW in a few years. It looks like BMJ has published a study showing SJW's efficacy. Although, there was some concerns voiced.

Another apology. The NEJM did not publish a recent SJW study. It was a couple of (JAMA-1 & JAMA-2) a few years back that made news. These studies were what my faulty memory remembered.

Using the same preparation of SJW a clinical trial in American Journal of Psychiatry also showed efficacy for SJW.

The above studies used specially prepared extract of SJW. I am not sure that this product is available for sale in Canada or the US. Although I did find one product claiming to be better thanthe WS 5570 extract used in the studies. Most commercially available preparations are not made with the same exacting standards as those used in the above trials. Herbal products are unregulated; as such they are not manufactured to the same standards required by medications. Thus, one cannot be certain that one is buying a product with similar efficacy as those used in the above studies.

Furthermore, the Cochrane Library is not convinced that SJW is an effective treatment. The Cochrane Library is a collection of databases that contain high-quality, independent evidence to inform healthcare decision-making. Cochrane reviews represent the highest level of evidence on which to base clinical treatment decisions and is the most trusted of evidence-based medicine databases.

I do not believe that I'd ever use or trust commercially available preparations of SJW, but far be it for me to stop anyone else from doing so. I am not fully convinced that SJW is as safe and effective as some studies suggest. Granted, this is only my personal opinion.

Again, I apologize for not checking my facts before posting. My memory ain't what it used to be. I hope that you'll forgive me. Sincerely - Cam

Hey Cam. No problemo, I'll admit that I've never personally researched St John's Wort before. I was going solely by word of mouth and I guess I was just lucky this time that they had done their research. Quite often I turn out to be wrong and it does indeed seem that the issue is more controversial than I thought it was.

I have heard that getting decent products can indeed be a problem. I could be completely wrong on this... But I have some notion that it might be the case that Canadian laws on non-prescription medications are tighter than the US (with respect to false advertising on the bottle) and thus I've heard that a number of people choose to purchase St John's Wort through Canadian rather than USA sources. But that could be a folk notion. I have no idea. I'm from the Southern Hemisphere and I have no idea what the situation here is (unregulated I guess but I don't know).

I didn't know about the Cochrane library, so thanks for that.

I've been following the literature on Hypericum perforatum (St. John's wort) for some time. I am absolutely surprised at how little "press time" is given to successful SJW trials, whereas negative outcomes receive massive publicity. I'd like to present some of those positive studies.....

The follow-up maintenance phase for the above-referenced BMJ study has been published, and the numbers for the St. John's wort group were better than those of paroxetine in the longer trial, as well:
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=17124643

There have been studies which show superiority of hypericum over fluoxetine (Prozac):

http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16160619
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15458612
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=10759336

It should be noted that a recent Brazilian study showed no benefit from SJW versus placebo, but that fluoxetine (active comparator) also failed in that comparison:
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16612487

When active comparators also do not exceed placebo response rates, one must question methodology first. Let's just say that there are more questions raised than answers provided.

Another recent study show non-inferiority of SJW compared to citalopram (Celexa):
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16555167

Many successful comparisons have been made with sertraline (Zoloft), unlike the negative JAMA study:
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15744631
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=12053635
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=10823363

Over the years, many comparisons with the quintessential tricyclic imipramine (Tofranil) have shown equivalence or superiority of SJW:
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=10968813
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=10591711
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9342765
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=7857502

With respect to the negative JAMA-published trial, the methodological flaws in that study are legendary. Most interesting was that the active comparator, sertraline, also led to lower remission rates than did placebo, but only the SJW results were emphasized in both the journal article (an incredibly unscientific lapse) and the lay press. Surely, the complete failure of an FDA-approved antidepressant was more note-worthy?

In the above references, SJW extracts were identified by cryptic letter/number codes. LI 160 is marketed in North America as Kira. WS5570/72/73 is Perika. I don't know the brand names of the others.

Given the number of unpublished studies which failed to show efficacy of prescription meds (FDA archives), I suspect that publication bias is responsible for the number of negative articles about SJW. It may be an herb, and it may act by unknown mechanisms (one completely novel global reuptake inhibitor effect, and three others which influence serotonin in a more targetted manner, already identified), but it has similar efficacy to other major antidepressant medications, and is less likely than any of them to produce side effects (higher tolerability). It also has no known toxic threshold, making overdose unlikely.

Just my analysis, as food for thought.....

Lar

Thanks for all that information. I'm going to mark this thread as a favorite.

I have to wonder if there might be some other variable at work, such as who chooses SJW vs. prescription meds or no meds (not that research subjects generally are given a choice since they are blind studies, but that would be something else to consider too in future studies). I'd like to speculate that people who choose SJW and are motivated to take charge of and participate in their own recovery would have better long-term outcomes than, say, someone who only goes to their family doctor for a prescription to manage symptoms. But there would be so much more involved too. Very severe depression might remove SJW as an option. And of course there are people who take charge of their own treatment and choose prescription meds. Nothing is ever simple, is it?

Thanks Lar - Good to hear from you. The info on Kira™ & Perika™ is much appreciated. Ya gotta spend the money if you want the efficacy. My opinion of SJW is bending.

Thanks again - Cam

hiya larry

long time no babble ;-)

(from each of us)

hope you are well

** bump

Here's another site to check: http://www.holisticonline.com/Herbal-Med/_Herbs/h20.htm

My MD once told me he was using wort for "mild depression" and he was happy with the results.

I've grown it for years but use it in a topical ointment I make along with two other herbs. It is EXCELLENT for this use - better than Neosporin!

I have had some degree of success with SJW, but please bear in mind it is more suitable for mild depression and S.A.D. Also bear in mind it can be expensive to buy the better brands which are apparently superior. The Kira brand is popular but pricey (in the UK). The only side effect I had was indigestion. Good luck !

I had a side effect from St. John's Wort -- I got pregnant while I was taking birth control pills. I took my pill at the same time everyday and never missed a day, so I was shocked when I got pregnant. It turns out St. John's Wort interferes with the efficacy of birth control pills. I didn't know that until AFTER I got pregnant. So, ever since then I have made sure that I check for any documented interactions with prescriptions meds I'm taking before I try any herbal supplements.

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blueeyedboy said:
I have had some degree of success with SJW, but please bear in mind it is more suitable for mild depression and S.A.D. Also bear in mind it can be expensive to buy the better brands which are apparently superior. The Kira brand is popular but pricey (in the UK). The only side effect I had was indigestion. Good luck !

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Umm, the reason I collected all those links together was to demonstrate that SJW was not just for mild depression. In head-to-head- comparisons with pharmaceutical antidepressant drugs, SJW performed as well or better than they did. It may be necessary to take more than the 900 mg/day dose, but you titrate any antidepressant to greatest efficacy. There is no toxic threshold to worry about with SJW.

Lar

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Juliana said:
I had a side effect from St. John's Wort -- I got pregnant while I was taking birth control pills. I took my pill at the same time everyday and never missed a day, so I was shocked when I got pregnant. It turns out St. John's Wort interferes with the efficacy of birth control pills. I didn't know that until AFTER I got pregnant. So, ever since then I have made sure that I check for any documented interactions with prescriptions meds I'm taking before I try any herbal supplements.

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I'm sorry you learned the hard way. SJW induces, or increases the activity of, liver enzyme 3A4. That's the same enzyme inhibited by grapefruit juice, so a simple rule of thumb is that if the grapefruit warning applies to any of your meds, it applies to SJW also.

In the case of birth control pills, SJW speeds up the clearance from the blood of the synthetic hormone that blocks ovulation. In some cases, the concentration falls low enough to no longer inhibit the ovaries.

It is indeed wise to check for interactions when taking any substance. Medicinal herbs are drugs, too.

Lar

Hi Larry. Thanks so much for the explanation of how SJW interferes with birth control pills. I wish my medical doctor had been as informed as you are.

I went hypomanic with it - and I had never had anything but depression... wasn't for me I guess...

Funny, I never remember to warn of manic induction. Any antidepressant can do that. Thanks for pointing that out. Hopefully, I'll now remember to do so, in the future.

Lar

Hello Larrykins. How are you today

I would love to try SJW again. It worked really well for me once upon a time.

But I don't wanna get preggers just at present ... knowing my luck I probably would :|

I guess maybe if I were completely single i would.