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PubMed1984

[Antidepressive effect of a Hypericum extract standardized to an active hypericine complex. Biochemical and clinical studies].

In 6 women with depressive symptoms aged 55-65 years the effect on the excretion of urinary metabolits of noradrenaline and dopamine was measured after a monotherapy with the active hypericine complex (Psychotonin M). In all patients there was a significant increase in 3-methoxy-4-hydroxyphenylglucol which is considered an expression of a beginning antidepressive reaction. With the same patients supplemented with further 9 cases the clinical influence on the depression was measured during a period of 4-6 weeks, with the rating-scales SCAG (Clinical assessment geriatric scale) and DSI (Depression Status Inventory) there was shown a quantitative improvement of the items anxiety, dysphoric mood, loss of interest, hypersomnia, anorexia, depression regularly worse in the morning, insomnia, obstipation, psychomotoric retardation and feeling of worthlessness.

Adult↗
PubMedDate not supplied

[The immunotropic properties of biologically active products obtained from Klamath weed (Hypericum perforatum L.)].

We carried out a systematic study of immunotropic activity of John's wort on the level of integrated fractions including all basic active substances of this plant. Both types of substances capable of increasing and suppressing the immunity were found in John's wort. Polyphenol fraction exhibits the immunostimulating activity with respect to the system of mononuclear phagocyte system, cellular and humoral immunity, and is capable of recovering the immune response in conditions of high-zone tolerance. Lipophilic fraction of this plant exhibits immunosuppressing properties with respect to cellular and humoral immune response. Immunotropic activity of polyphenol and lipophilic fractions correlate with their low toxicity.

Adjuvants, Immunologic↗
PubMed2000

Comparison of St John's wort and imipramine for treating depression: randomised controlled trial.

OBJECTIVES: To compare the efficacy and tolerability of Hypericum perforatum (St John's wort extract) with imipramine in patients with mild to moderate depression. DESIGN: Randomised, multicentre, double blind, parallel group trial. SETTING: 40 outpatient clinics in Germany. PARTICIPANTS: 324 outpatients with mild to moderate depression. INTERVENTION: 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily for 6 weeks. MAIN OUTCOME MEASURES: Hamilton depression rating scale, clinical global impression scale, and patient's global impression scale. RESULTS: Among the 157 participants taking hypericum mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point; among the 167 participants taking imipramine they fell from 22.1 to 12.75. Mean clinical global impression scores at end point were 2.22 out of 7 for the hypericum group and 2.42 for the imipramine group. On the 7 point self assessments of global improvement completed by participants (score of 1 indicating "very much improved" and 7 indicating "very much deteriorated") mean scores were 2.44 in the hypericum group and 2.60 in the imipramine group. None of the differences between treatment groups were significant. However, the mean score on the anxiety-somatisation subscale of the Hamilton scale (3.79 in the hypericum group and 4.26 in the imipramine group) indicated a significant advantage for hypericum relative to imipramine. Mean scores on the 5 point scale used by participants to assess tolerability (score of 1 indicating excellent tolerability and 5 indicating very poor tolerability) were better for hypericum (1.67) than imipramine (2.35). Adverse events occurred in 62/157 (39%) participants taking hypericum and in 105/167 (63%) taking imipramine. 4 (3%) participants taking hypericum withdrew because of adverse events compared with 26 (16%) taking imipramine. CONCLUSIONS: This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better.

Adult↗
PubMed2000

St John's wort for depression.

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.

Adult↗
PubMed2005

St John's wort for depression.

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 adverse effects than standard antidepressant drugs. SEARCH STRATEGY: Trials were searched in computerized databases (Cochrane Collaboration Depression, Anxiety & Neurosis Group Clinical Trials Registers; PubMed); by checking bibliographies of pertinent articles; and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were included if they: (1) were randomized and double-blind; (2) included patients with depressive disorders; (3) compared extracts of St. John's wort with placebo or standard 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 adverse effects was the number of patients dropping out for adverse effects. MAIN RESULTS: A total of 37 trials, including 26 comparisons with placebo and 14 comparisons with synthetic standard antidepressants, met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In trials restricted to patients with major depression, the combined response rate ratio (RR) for hypericum extracts compared with placebo from six larger trials was 1.15 (95% confidence interval (CI), 1.02-1.29) and from six smaller trials was 2.06 (95% CI, 1.65 to 2.59). In trials not restricted to patients with major depression, the RR from six larger trials was 1.71 (95% CI, 1.40-2.09) and from five smaller trials was 6.13 (95% CI, 3.63 to 10.38). Trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with selective serotonin reuptake inhibitors (SSRIs) and tri- or tetracyclic antidepressants, respectively, RRs were 0.98 (95% CI, 0.85-1.12; six trials) and 1.03 (95% CI, 0.93-1.14; seven trials). Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (Odds ratio (OR) 0.25; 95% CI, 0.14-0.45); such comparisons were in the same direction, but not statistically significantly different, between hypericum extracts and SSRIs (OR 0.60, 95% CI, 0.31-1.15). AUTHORS' CONCLUSIONS: Current evidence regarding hypericum extracts is inconsistent and confusing. In patients who meet criteria for major depression, several recent placebo-controlled trials suggest that the tested hypericum extracts have minimal beneficial effects while other trials suggest that hypericum and standard antidepressants have similar beneficial effects. As the preparations available on the market might vary considerably in their pharmaceutical quality, the results of this review apply only to the products tested in the included studies.

Adult↗
PubMed2000

Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression.

Treatment with St John's wort extract tablets (hypericum Ze 117) and the commonly used slow serotonin reuptake inhibitor (SSRI) fluoxetine was compared in patients with mild-moderate depression with entry Hamilton Depression Scale (HAM-D) (21-item) in the range 16-24, in a randomized, double-blind, parallel group comparison in 240 subjects; fluoxetine: 114 (48%), hypericum: 126 (52%). After 6 weeks' treatment, mean HAM-D at endpoint decreased to 11.54 on hypericum and to 12.20 on fluoxetine (P < 0.09), while mean Clinical Global Impression (CGI) item I (severity) was significantly (P < 0.03) superior on hypericum, as was the responder rate (P = 0.005). Hypericum safety was substantially superior to fluoxetine, with the incidence of adverse events being 23% on fluoxetine and 8% on hypericum. The commonest events on fluoxetine were agitation (8%), GI disturbances (6%), retching (4%), dizziness (4%), tiredness, anxiety/nervousness and erectile dysfunction (3% each), while on hypericum only GI disturbances (5%) had an incidence greater than 2%. We concluded that hypericum and fluoxetine are equipotent with respect to all main parameters used to investigate antidepressants in this population. Although hypericum may be superior in improving the responder rate, the main difference between the two treatments is safety. Hypericum was superior to fluoxetine in overall incidence of side-effects, number of patients with side-effects and the type of side-effect reported.

Adult↗
PubMed2004

Adverse effects of St. John's Wort: a systematic review.

OBJECTIVE: To obtain an overview of the available clinical evidence on safety and tolerability of hypericum extracts, we reviewed (1) dropout rates and adverse effects in double-blind randomized trials comparing hypericum extracts and placebo or synthetic standard antidepressants; (2) dropout rates and adverse effects in large-scale observational studies; and (3) adverse effects reported in published cases and to public drug surveillance agencies. METHOD: Data on dropout rates and adverse effects were extracted from double-blind randomized trials of hypericum monopreparations collected for a Cochrane review (last search July 2003) and from a PubMed search (text word hypericum; search dates 1998-January 2003). Similar data were extracted from uncontrolled observational studies including at least 100 patients identified through a PubMed search (search term hypericum NOT animal, last update May 2003), contacts with manufacturers, and screening of review articles. Case reports and case series on adverse events associated with hypericum products were identified through a MEDLINE search (1966-November 2002; search term: hypericum AND [adverse effects OR interaction]) and a PubMed search (February 2003) and were collected from 5 public drug surveillance agencies (data through May 2001). All database searches were conducted as English and non-English language searches. RESULTS: Data from 35 double-blind randomized trials showed that dropout and adverse effects rates in patients receiving hypericum extracts were similar to placebo, lower than with older antidepressants, and slightly lower than with selective serotonin reuptake inhibitors. Dropout rates due to adverse effects in 17 observational studies including 35,562 patients ranged from 0% to 5.7%; interactions or serious adverse effects were not reported in any study. Published cases and cases reported to drug surveillance agencies suggest that interactions with a variety of drugs (particularly cyclosporine in transplant patients) are the most relevant adverse effects of hypericum extracts. CONCLUSIONS: The available evidence suggests that hypericum extracts are well tolerated and safe if taken under control of a physician who is aware of potentially relevant risks in specific circumstances.

Antidepressive Agents↗
PubMed2001

St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats.

Clinical studies demonstrate that the antidepressant efficacy of St John's wort (Hypericum) is comparable to that of tricyclic antidepressants such as imipramine. Onset of efficacy of these drugs occurs after several weeks of treatment. Therefore, we used in situhybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract, and hypericin (an active constituent of St John's wort) on the expression of genes that may be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine (15 mg kg(-1)), Hypericum (500 mg kg(-1)), and hypericin (0.2 mg kg(-1)) given daily by gavage for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 16-22% in the hypothalamic paraventricular nucleus (PVN) and serotonin 5-HT(1A) receptor mRNA by 11-17% in the hippocampus. Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three compounds on gene transcription suggests a shared action on the centers that control HPA axis activity. A second study was performed to assess the effects of long-term imipramine and Hypericum administration on stress-induced changes in gene transcription in stress-responsive circuits. Repeated immobilization stress (2 h daily for 7 days) increased mRNA levels of CRH in the PVN, proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus. It decreased mRNA levels of 5-HT(1A) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Long-term pre-treatment with either imipramine or Hypericum reduced to control levels the stress-induced increases in gene transcription of GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum. The stress-induced decreases in BDNF and 5-HT(1A)mRNA levels were not prevented by either drug. Taken together, these data show: (1) that Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine; and (2) that select stress-induced changes in gene transcription in particular brain areas can be prevented by long-term treatment with either the prototypic tricyclic antidepressant imipramine or the herbiceutical St John's wort. However, imipramine appears to be more effective in blocking stress effects on the HPA axis than the plant extract.

Adrenal Glands↗
PubMed2001

In vivo neurotransmitter release in the locus coeruleus--effects of hyperforin, inescapable shock and fear.

Hyperforin, the main antidepressant constituent of Hypericum perforatum, influences the extracellular concentrations of transmitters in vitro and in vivo. In vivo experiments have shown that hyperforin enhances the extracellular concentrations of dopamine, norepinephrine, serotonin and glutamate in the locus coeruleus. Hyperforin-free Hypericum extract also elevates the extracellular concentrations of dopamine and norepinephrine in the locus coeruleus, but, in contrast to hyperforin, the extracellular concentration of serotonin is diminished. The differing profiles of hyperforin and hyperforin-free Hypericum extract on the extracellular transmitter concentrations point to the presence of an additional biologically active compound in Hypericum perforatum. Inescapable shock increases the release of monoamines and several amino acids, as well as motility, blood pressure and heart rate. Conditioned fear, similar to hyperforin-free Hypericum extract, decreases the release of serotonin in the locus coeruleus. Conditioned fear also leads to tachycardia. The latter finding shows that telemetric heart rate recording is a good index for conditioned fear. In vivo findings confirm the idea that the anti-depressive properties of Hypericum extract and hyperforin result from increases in extracellular neurotransmitter concentrations. Since hyperforin-free extract, like conditioned fear, reduces the extracellular concentration of serotonin, hyperforin may be more beneficial than Hypericum extract in the treatment of depressive disorders.

Animals↗
PubMed2003

Topical treatment of atopic dermatitis with St. John's wort cream--a randomized, placebo controlled, double blind half-side comparison.

BACKGROUND: Recent investigations suggest an anti-inflammatory and antibacterial effect of hyperforin, which is a major constituent of Hypericum perforatum L. (Saint John's wort). OBJECTIVE: In the present half-side comparison study we assessed the efficacy of a cream containing Hypericum: extract standardised to 1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for the treatment of subacute Atopic Dermatitis. The study design was a prospective randomised placebo-controlled double-blind monocentric study. METHODS: In twenty one patients suffering from mild to moderate Atopic Dermatitis (mean SCORAD 44.5) the treatment with verum or placebo was randomly allocated to the left or right site of the body, respectively. The patients were treated twice daily over a period of four weeks. Eighteen patients completed the study. The severity of the skin lesions on the left and right site was determined by means of a modified SCORAD-index (primary endpoint). RESULTS: The intensity of the eczematous lesions improved on both sites of treatment. However, the hypericum-cream was significantly superior to the vehicle at all clinical visits (days 7, 14, 28) (p < 0.05). Skin colonisation with Staphylococcus aureus was reduced by both verum and placebo, showing a trend to better antibacterial activity of the hypericum-cream (p = 0.064). Skin tolerance and cosmetic acceptability was good or excellent with both the hypericum-cream and the vehicle (secondary endpoints). CONCLUSION: Taken together, the present study shows a significant superiority of the hypericum-cream compared to the vehicle in the topical treatment of mild to moderate Atopic Dermatitis. The therapeutic efficacy of the hypericum-cream, however, has to be evaluated in further studies with larger patient cohorts, in comparison to therapeutic standards (i.e. glucocorticoids).

Administration, Cutaneous↗
PubMed2005

St John's wort for depression: meta-analysis of randomised controlled trials.

BACKGROUND: Extracts of Hypericum perforatum (St John's wort) are widely used to treat depression. Evidence for its efficacy has been criticised on methodological grounds. AIMS: To update evidence from randomised trials regarding the effectiveness of Hypericum extracts. METHODS: We performed a systematic review and meta-analysis of 37 double-blind randomised controlled trials that compared clinical effects of Hypericum monopreparation with either placebo or a standard antidepressant in adults with depressive disorders. RESULTS: Larger placebo-controlled trials restricted to patients with major depression showed only minor effects over placebo, while older and smaller trials not restricted to patients with major depression showed marked effects. Compared with standard antidepressants Hypericum extracts had similar effects. CONCLUSIONS: Current evidence regarding Hypericum extracts is inconsistent and confusing. In patients who meet criteria for major depression, several recent placebo-controlled trials suggest that Hypericum has minimal beneficial effects while other trials suggest that Hypericum and standard antidepressants have similar beneficial effects.

Antidepressive Agents↗
PubMed2003

Effect of oral administration ofHypericum perforatum extract (St. John's Wort) on skin erythema and pigmentation induced by UVB, UVA, visible light and solar simulated radiation.

Hypericin from St John's wort (Hypericum perforatum L.) is a photosensitizing agent that may cause a severe photodermatitis when higher amounts of St John's wort are ingested by animals. Although Hypericum extracts are widely used in the treatment of depressive disorders, only a little information on the photosensitizing capacity of St John's wort in humans is available. In the present prospective randomized study we investigated the effect of the Hypericum extract LI 160 on skin sensitivity to ultraviolet B (UVB), ultraviolet A (UVA), visible light (VIS) and solar simulated radiation (SIM). Seventy two volunteers of skin types II and III were included and were divided into six groups, each consisting of 12 volunteers. In the single-dose study the volunteers (n = 48) received 6 or 12 coated tablets (5400 or 10 800 microgram hypericin). In the steady-state study the volunteers (n = 24) received an initial dose of 6 tablets (5400 microgram hypericin), and subsequently 3 x 1 tablets (2700 microgram hypericin) per day for 7 days. Phototesting was performed on the volar forearms prior to medication and 6 h after the last administration of Hypericum extract. The erythema-index and melanin-index were evaluated photometrically using a mexameter. After both single-dose and steady-state administration, no significant influence on the erythema-index or melanin-index could be detected, with the exception of a marginal influence on UVB induced pigmentation (p = 0.0471) in the single-dose study. The results do not provide evidence for a phototoxic potential of the Hypericum extract LI 160 in humans when administered orally in typical clinical doses up to 1800 mg daily. This is in accordance with previous pharmacokinetic studies that found hypericin serum and skin levels after oral ingestion of Hypericum extract always to be lower than the assumed phototoxic hypericin threshold level of 1000 ng/mL.

Administration, Oral↗