Posted by Larry Hoover on December 7, 2003, at 7:17:11
In reply to St. John's Wort - Is it worth while?, posted by JimD on December 4, 2003, at 8:18:11
> I've been struggling with mild depression and am trying to avoid going on meds. I understand that St. John's Wort has been proven in some studies to alleviate symptoms of mild-moderate depression.
I have pasted in some relevant abstracts below.
> Does anyone have any experience with SJW? Has it proven to be effective?
It was the best antidepressant I've ever used, period.
I am a major advocate of SJW....I'm sorry I came late to this discussion. There are two main active ingredients in SJW extracts, hypericin and hyperforin, but recent work has shown that even if those compounds are removed from SJW extract, the remaining substances still show potent antidepressant activity. Down below is a nice summary of the various effects of SJW extract....virtually every neurotransmitter yet identified is affected directly at receptors, or indirectly at the gene regulatory level....but not with the typical sledge-hammer effect of prescription drugs....broader, and more gentle.
Down below, you'll find a meta-analysis of the research into SJW, done by Cochrane Reviews. The Cochrane people are the absolutely most conservative review group in existence. Studies must meet the strictest methodological standards, or they're simply not considered. The Cochrane people are satisfied that SJW stands up to other antidepressants (the RR of 1.01 statistic means they are identical (1.0 is perfectly equivalent)), but that more research is needed to make the conclusion ironclad. The Cochrane review includes only those studies done before 1998, so I'm sure that they have many more to consider if they revisit the issue now.> I also understand that it is important to use a 'brand you can trust,' given that it is not regulated by the FDA. Any recommendations?
You may want to choose Perika, which is a German product (where herbal products *are* regulated) marketed here by Nature's Way.
> Thanks!Interesting, is it not, how there was so much press given to the heavily flawed American studies published in JAMA, declaring SJW ineffective, while other studies in respected journals which demonstrate efficacy have been ignored? (The Canadian study compared the very same drugs, sertraline and SJW, but came up with a very different result.) Interesting too that the JAMA work was funded by one of the largest pharmaceutical companies in the world...
Am J Psychiatry. 2002 Aug;159(8):1361-6.
Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial.Lecrubier Y, Clerc G, Didi R, Kieser M.
Unite Institut National de la Sante et de la Recherche Medicale 302, Hopital Pitie Salpetriere, Paris, France. lecru@ext.jussieu.fr
OBJECTIVE: In a double-blind, randomized, placebo-controlled trial with 375 patients the authors investigated the antidepressant efficacy and safety of 300 mg t.i.d. of hydroalcoholic Hypericum perforatum extract WS 5570. METHOD: The study participants were male and female adult outpatients with mild to moderate major depression (single or recurrent episode, DSM-IV criteria). After a single-blind placebo run-in phase, the patients were randomly assigned, 186 to WS 5570 and 189 to placebo, after which they received double-blind treatment for 6 weeks. Follow-up visits were held after 1, 2, 4, and 6 weeks. The primary outcome measure was the change from baseline in the total score on the 17-item Hamilton Depression Rating Scale. In addition, analyses of responders (patients with at least a 50% reduction in Hamilton total score) and patients with remissions (patients with a total score of 6 or less on the Hamilton scale at treatment end) were carried out, and subscale/subgroup analyses were conducted. The design included an adaptive interim analysis performed after random assignment of 169 patients with options for group size adjustment or early termination. RESULTS: Compared to placebo, WS 5570 produced a significantly greater reduction in total score on the Hamilton depression scale and significantly more patients with treatment response or remission. It was more effective in patients with higher baseline Hamilton scores and led to global reduction of depression-related core symptoms, assessed with the melancholia subscale of the Hamilton scale. The placebo and WS 5570 groups had comparable adverse events. CONCLUSIONS: H. perforatum extract WS 5570 was found to be safe and more effective than placebo for the treatment of mild to moderate depression.
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. gerald.vangurp@mcgill.ca
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.
Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S38-41.
Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort.
Friede M, Henneicke von Zepelin HH, Freudenstein J.
Schaper & Brummer GmbH & Co. KG, Salzgitter, Germany.
The purpose of this report was to evaluate specific depressive symptoms that are most suitable for a therapy with the Ze 117 St. John's wort extract. We examined the antidepressant efficacy and drug safety of Ze 117 and fluoxetine in a multicentric prospective randomized double-blind parallel group comparison according to generally accepted guidelines such as the Declaration of Helsinki and GCP. We treated outpatients (n = 240; Ze 117: 126; fluoxetine: 114) with mild to moderate depressive episodes (ICD-10: F 32.0, F 32.1; HAMD range: 16-24) with either two tablets St John's wort (Ze 117; 500 mg extract/day) or fluoxetine (20 mg/day) for 6 weeks. Antidepressant efficacy was evaluated with the validated HAMD psychometric method. A validated analysis of HAMD subscores was made to verify the efficacy for certain depressive symptoms. The main results were: * The HAMD responder rate was 60% in the Ze 117 group compared to 40% in the fluoxetine group (p = 0.005). * Particularly, there was a marked decrease of depressive agitation (pre-post comparison: 46%) and anxiety symptoms (44%) during the therapy with St. John's wort. Depressive obstruction (44%) and sleep disorders (43%) were reduced during the treatment, too. There were no statistically significant differences between the treatment groups. * Adverse events occurred in 28 patients (25%) in the fluoxetine group and in 18 (14%) of the St. John's wort group (p < 0.07). St. John's wort extract is a clinically effective equivalent to fluoxetine regarding overall depressive symptoms and main symptoms of depressive episodes. An especially interesting overall observation is that Ze 117 is particularly effective in depressive patients suffering from anxiety symptoms. St. John's wort revealed better safety and tolerability data than fluoxetine.
Int Clin Psychopharmacol. 2001 Sep;16(5):239-52.
A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review.Whiskey E, Werneke U, Taylor D.
Pharmacy Department, Maudsley Hospital, London, UK.
The herbal remedy St John's wort is widely used as an antidepressant but its efficacy has not been systematically investigated. Meta-analyses and systematic reviews of published trials strongly suggest St John's wort is more effective than placebo although comparative efficacy to standard antidepressants is less clearly established. We updated and expanded previous meta-analyses of St John's wort, scrutinised the validity of published reports and examined possible mechanisms of action. Twenty-two randomised controlled trials were identified. Meta-analysis showed St John's wort to be significantly more effective than placebo (relative risk (RR) 1.98 (95% CI 1.49-2.62)) but not significantly different in efficacy from active antidepressants (RR 1.0 (0.90-1.11)). A sub-analysis of six placebo-controlled trials and four active comparator trials satisfying stricter methodological criteria also suggested that St John's wort was more effective than placebo (RR 1.77 (1.16-2.70)) and of similar effectiveness to standard antidepressants (RR 1.04 (0.94-1.15)). There was no evidence of publication bias. Adverse effects occurred more frequently with standard antidepressants than with St John's wort. The mechanism of action of St John's wort remains unknown. Future research should include large scale, appropriately powered comparisons of St John's wort and standard antidepressants.
CNS Drugs. 2003;17(8):539-62.
Mechanism of action of St John's wort in depression : what is known?
Butterweck V.
Institute of Pharmacology and Toxicology, Universitatsklinikum Munster, Munster, Germany. butterv@uni-muenster.de
Extracts of Hypericum perforatum L. (St John's wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John's wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones. Although St John's wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John's wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, other in vitro binding assays carried out using St John's wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors. In vivo St John's wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John's wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John's wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John's wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John's wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids. This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John's wort and its active constituents with a large body of existing literature.
Cochrane Database Syst Rev. 2000;(2):CD000448.
St John's wort for depression.
Linde K, Mulrow CD.
Munchener Modell - Centre for Complementary Medicine Research, Technical University/Ludwig-Maximilians-University, Kaiserstr. 9, Munich, Germany, 80801. Muenchener.Modell@lrz.uni-muenchen.de
BACKGROUND: Extracts of the plant Hypericum perforatum L. (popularly called St. John's wort) have been used in folk medicine for a long time for a range of indications including depressive disorders. OBJECTIVES: To investigate whether extracts of Hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of depressive disorders in adults; and whether they have have less side effects than standard antidepressant drugs. SEARCH STRATEGY: Trials were searched in computerized general (Medline, Embase, Psychlit, Psychindex) and specialized databases (Cochrane Complementary Medicine Field, Cochrane Depression & Neurosis CRG, Phytodok); by checking bibliographies of pertinent articles; and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were included if they: (1) were randomized; (2) included patients with depressive disorders; (3) compared preparations of St. John's wort (alone or in combination with other plant extracts) with placebo or other antidepressants; and (4) included clinical outcomes such as scales assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, outcomes and results was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Hypericum with placebo and standard antidepressants was the responder rate ratio (responder rate in treatment group/responder rate in control group). The main outcome measure for side effects was the number of patients reporting side effects. MAIN RESULTS: 27 trials including a total of 2291 patients met inclusion criteria. 17 trials with 1168 patients were placebo-controlled (16 addressed single preparations, one a combination with four other plant extracts). Ten trials (eight single preparations, two combinations of hypericum and valeriana) with 1123 patients compared hypericum with other antidepressant or sedative drugs. Most trials were four to six weeks long. Participants usually had "neurotic depression" or "mild to moderate severe depressive disorders." Hypericum preparations were significantly superior to placebo (rate ratio 2.47; 95% confidence interval 1.69 to 3.61) and similarly effective as standard antidepressants (single preparations 1.01; 0.87 to 1.16, combinations 1.52; 0.78 to 2.94). The proportions of patients reporting side effects were 26.3% for hypericum single preparations vs. 44.7% for standard antidepressants (0.57; 0.47 to 0.69), and 14. 6% for combinations vs. 26.5% with amitriptyline or desipramine (0. 49; 0.23 to 1.04). REVIEWER'S CONCLUSIONS: There is evidence that extracts of hypericum are more effective than placebo for the short-term treatment of mild to moderately severe depressive disorders. The current evidence is inadequate to establish whether hypericum is as effective as other antidepressants. Further studies comparing hypericum with standard antidepressants in well defined groups of patients over longer observations periods, investigating long term side effects, and comparing different extracts and doses are needed.
poster:Larry Hoover
thread:286464
URL: http://www.dr-bob.org/babble/alter/20031204/msgs/287357.html