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St. John's Wort for Depression

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Abstract

Studies concluding that St. John's wort (Hypericum perforatum) is an effective antidepressant can be challenged due to questionable methodology. We attempt to correct this by a meta-analysis utilizing only well-defined clinical trials. Controlled, double-blind studies using strictly defined depression criteria were analyzed by the rate of change of depression and by the number of "treatment responders." Rates of side effects and dropouts were also analyzed. Hypericum was 1.5 times more likely to result in an antidepressant response than placebo and was equivalent to tricyclic antidepressants (TCAs). The meta-analysis also showed that there was a higher dropout rate in the TCA group and that the TCAs were nearly twice as likely to cause side effects, including those more severe than hypericum. Hypericum perforatum was more effective than placebo and similar in effectiveness to low-dose TCAs in the short-term treatment of mild to moderately severe depression. However, design problems in existing studies prevent definitively concluding that St. John's wort is an effective anti-depressant.

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... St. John's Wort (H. perforatum L.) is used as a complementary medicine for mild depression (Linde et al., 1996;Kim et al., 1999;Linde and Mulrow, 2000) and some psychiatric indications (Martinez et al., 1994;Kasper, 1997;Taylor and Kobak, 2000). There is some evidence for minimal risk of St. John Wort's use in pregnancy (Grush et al., 1998). ...
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About 80% of the consumers worldwide use herbal medicine (HMs) or other natural products. The percentage may vary significantly (7%–55%) among pregnant women, depending upon social status, ethnicity, and cultural traditions. This manuscript discusses the most common HMs used by pregnant women, and the potential interactions of HMs with conventional drugs in some medical conditions that occur during pregnancy (e.g., hypertension, asthma, epilepsy). It also includes an examination of the characteristics of pregnant HM consumers, the primary conditions for which HMs are taken, and a discussion related to the potential toxicity of HMs taken during pregnancy. Many cultures have used HMs in pregnancy to improve wellbeing of the mother and/or baby, or to help decrease nausea and vomiting, treat infection, ease gastrointestinal problems, prepare for labor, induce labor, or ease labor pains. One of the reasons why pregnant women use HMs is an assumption that HMs are safer than conventional medicine. However, for pregnant women with pre-existing conditions like epilepsy and asthma, supplementation of conventional treatment with HMs may further complicate their care. The use of HMs is frequently not reported to healthcare professionals. Providers are often not questioning HM use, despite little being known about the HM safety and HM-drug interactions during pregnancy. This lack of knowledge on potential toxicity and the ability to interact with conventional treatments may impact both mother and fetus. There is a need for education of women and their healthcare professionals to move away from the idea of HMs not being harmful. Healthcare professionals need to question women on whether they use any HMs or natural products during pregnancy, especially when conventional treatment is less efficient and/or adverse events have occurred as herbal-drug interactions could be the reason for these observations. Additionally, more preclinical and clinical studies are needed to evaluate HM efficacy and toxicity.
... Despite this multiplicity of biological actions, the primary indication of Hypericum perforatum extract, according to modern diagnostic criteria, is depression. Numerous clinical studies and meta-analyses have confirmed that Hypericum perforatum is effective in the treatment of mild to moderate depression and represents an accepted alternative to synthetic antidepressants or behavioural therapy [9,10]. ...
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Extracts of Hypericum perforatum (St. John's wort) have gained popularity as an alternative to synthetic antidepressants or behavioural therapy in the treatment of mild to moderate forms of depressive disorders. The present article reviews and discusses the available preclinical data that are in favour of or against the use of Hypericum perforatum as an antidepressant. Multiple chemical entities constitute extracts from Hypericum perforatum. The effects of Hypericum perforatum extracts have been compared with those of conventional antidepressants in different in vitro and in vivo biochemical studies of antidepressant-like activity and in behavioural pharmacology studies using animal models of depression. Recent investigations have indicated that Hypericum perforatum, like conventional antidepressants, is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function and influence, at least in part, stress-induced effects on neuroplasticity and neurogenesis. From the available evidence it can be concluded that data supporting the use of Hypericum perforatum for the treatment of depression are present in literature. However, results from experiments carried out with extracts or pure compounds do not always resemble biochemical and pharmacological profile characteristic of synthetic antidepressants. In particular, the majority of findings in preclinical studies have been obtained with high doses of pure compounds and extracts that are not comparable to the concentrations of single active constituents after oral administration in humans.
... The plant is known to possess antidepressive activity as it inhibits serotonin reuptake and has recently been reported that it may serve as an effective treatment for mild to moderate depression (6). Studies have shown that SJW exhibits antidepressant like effects in experimental animal models of depression -such as the forced swim test (FST) (7). ...
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Stress, via corticosteroids release, influences bone mass density. Hypericum perforatum (Hp) a traditional remedy possess antidepressive activity (serotonin reuptake inhibitor) and wound healing properties. Hp preparation contains mainly hypericin, hyperforin, hyperoside and of stress associating mental strain and corporal exhaustion. Objectives. This study investigates the Hp effect on femur and mandible bone mass changes in rats under cold forced swimming procedure. Methods. 30 male Wistar rats were randomized into three groups. Group A was treated with Methanolic extract of Hp (Jarsin®) via gastroesophageal catheter, and was submitted to cold swimming stress for 10 min/daily. Group B was submitted to cold stress, since group C served as control. Experiment duration was 10 days. Haematocrite and serum free as bone mass density via dual energy X-Ray absorptiometry (DEXA) were measured. Statistic analysis by t-test. Results. Hp treatment restores the stress injuries. Adrenals and bone mass density regain their normal values. Conclusions. Injuries occurring by forced swimming stress in the rats are significantly improved by Hp treatment. Estrogen-like effects of Hp flavonoids eventually may act favorable in bone remodeling.
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The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with complementary and alternative medicines. Meta-analyses of randomized controlled trials have found Hypericum perforatum preparations to be superior to placebo and similarly effective as standard antidepressants in the acute treatment of mild to moderate depression. A clear advantage over antidepressants has been demonstrated in terms of the reduced frequency of adverse effects and lower treatment withdrawal rates, low rates of side effects and good compliance, key variables affecting the cost-effectiveness of a given form of therapy. The most important risk associated with use is potential interactions with other drugs, but this may be mitigated by using extracts with low hyperforin content. As the indirect costs of depression are greater than five times direct treatment costs, given the rising cost of pharmaceutical antidepressants, the comparatively low cost of Hypericum perforatum extract makes it worthy of consideration in the economic evaluation of mild to moderate depression treatments.
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In diesem Kapitel sind die bislang entwickelten und relevanten Antidepressiva zusammengestellt. Ziel dieser Übersicht ist, dem Leser einen schnellen Zugriff auf die wichtigsten Informationen für den klinischen Alltag zu ermöglichen. Zur Bedeutung der einzelnen Substanzen für therapieresistente Depressionen sei auf die jeweiligen Kapitel im Buch verwiesen.
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Herbal medicines include a range of pharmacologically active compounds: in some cases it is not well understood which ingredients are important for a therapeutic effect. The supporters of herbal medicine believe that isolated ingredients in the majority of cases have weaker clinical effects than whole plant extract, a claim that would obviously require proof in each case. Generalizations about the efficacy of herbal medicines are clearly not possible. Each one needs systematic research including a variety of animal studies and also randomized clinical trials. Indeed, clinical trials of herbal medicines are feasible much in the same way as for other drugs (Schulz, Hansel & Tyler, 1998). Numerous randomized clinical trials of herbal medicines have been published and systematic review and meta-analyses of these studies are available. Many of today's synthetic drugs originated from the plant kingdom, and only about two centuries ago the major pharmacopoeias were dominated by herbal drugs. Herbal medicine went into rapid decline when basic and clinical pharmacology established themselves as leading branches of medicine. Nevertheless, herbal medicine is still of interest in many diseases in particular psychiatric and neurological disorders. There are some reasons for this: (1) participants are dissatisfied with conventional treatment, (2) participants want to have control over their healthcare decisions, and (3) participants see that herbal medicine is congruent with their philosophical values and beliefs (Astin, 1998). It has been reported that most participants with a mental disorder sought herbal medicine treatment for somatic problems rather than for their mental and emotional symptoms and the best example is somatic symptoms of depression.
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In Hypericumspecies some specimens have been found to display higher levels of the toxic heavy metal Cd than the proposed guide value of 0.5mgkg. Plant and soil samples from various regions in Eastern Austria were collected to study the variability in the Cd content of the herbs and relate it to selected soil properties and soil micronutrient contents. The soils contained between 0.01 and 0.44mgkg−1Cd in the dry soil. Altogether about 7% of the collected plant samples exceeded 0.5mgkg−1Cd of dry shoots, the proposed guide value for the drug Herba Hyperici. Plants low in Cd were found on sites in the Alpenvorland, the Hainburger Berge, the Eastern Viennese Basin and the Northern Limestone Alps where the levels did not exceed 0.3mgkg−1Cd of dry shoots. Higher Cd levels in the plants were present in material from the Waldviertel, the Southern Wienerwald and the Semmering region where often bioaccumulation factors for Cd above 1 could be calculated. In these regions the soil pH and carbonate content was somewhat lower than in other regions whereas the soil organic carbon varied greatly. In the Waldviertel some plants from a field were somewhat higher in Cd than nearby plants from the natural vegetation. In a regression analysis, the soil pH, soil organic carbon and soil Cd content were the main factors influencing Cd accumulation in the plant shoots.
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St. John’s wort (SJW), known botanically as Hypericum perforatum, is a sprawling, leafy herb that grows in open, disturbed areas throughout much of the world’s temperate regions. The use of this species as an herbal remedy to treat a variety of internal and external ailments dates back to the time of the ancient Greeks. Since then, it has remained a popular treatment for anxiety, depression, cuts, and burns. Recent research suggests the effectiveness of this herb in treating other ailments, including cancer, inflammation-related disorders, and bacterial and viral diseases, and as an antioxidant and neuroprotective agent. Pharmaceutical companies, particularly in Europe, prepare standard formulations of this herb that are taken by millions of people. Worldwide annual sales of products made from SJW presently exceed several billion dollars. Further, SJW produces dozens of biologically active substances, although two—hypericin (a naphthodianthrone) and hyperforin (a lipophilic phloroglucinol)—have the greatest medical activity. Other compounds, including the flavonoids rutin, quercetin, and kaempferol, also appear to have medical activity. H. perforatum has been intensively studied on isolated tissue samples, using animal models and through human clinical trials. The effectiveness of SJW as an antidepression agent is particularly well studied, and the underlying mechanisms are well understood. SJW preparations have relatively few adverse effects when taken alone at the recommended dosages. However, numerous interactions with other drugs have been reported. Recent research shows these interactions result from the ability of SJW constituents to induce intestinal or hepatic enzymes that either remove drugs from the body or metabolize them to inactive forms. This chapter examines the constituents, modes of action, and adverse interactions of SJW, providing an up-to-date synthesis of a large body of literature that has developed over the past 30 years regarding this widely taken herbal remedy. Some recommendations regarding future research needs are also presented.
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St. John's Wort is a herbal therapy, shown to be effective in treating mild to moderate depression; a disease common in women in their childbearing years. With a significant proportion of unplanned pregnancies, exposure to St. John's Wort into pregnancy is expected to occur. The purpose of this study was to determine whether exposure to this agent in pregnancy is associated with major malformations. We prospectively collected and followed subjects taking St. John's Wort and compared them to a matched group of pregnant women taking other pharmacologic therapy for depression and a third group of healthy women, not exposed to any known teratogens. We obtained follow-up information on 54 St. John's Wort exposed pregnancies and 108 pregnancies in the two comparator groups. Our results indicated that the rates of major malformations were similar across the three groups, with 5%, 4% and 0% in the St. John's Wort, disease comparator, and health group, respectively (p=0.26), This was not different that the 3-5% risk expected in the general population. The live birth and prematurity rates were also not different among the three groups. Though further large scale studies are still needed, this first study on the effects of St. John's Wort in human pregnancy does provide some evidence of fetal safety.
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Long-term safety and the effects of a St. John's wort (SJW) extract Ze 117 (Hypericum perforatum) were evaluated in the treatment of patients with depression. An open multicentre safety study with 440 out-patients suffering from mild to moderate depression according to ICD-10 was conducted. Patients were treated for up to 1 year with 500 mg St. John's wort extract per day (Ze 117). Evaluation criteria were safety (adverse event frequency) and influence on depression (HAM-D, CGI). Two hundred and seventeen (49%) patients reported 504 adverse events, 30 (6%) of which were possibly or probably related to the treatment. Gastrointestinal and skin complaints were the most common events associated with treatment. No age-related difference in the safety of the applied medication was found. The long-term intake of up to 1 year of the study medication did not result in any changes in clinical chemistry and electrocardiogram recordings. Body mass index (BMI) did not change either. Mean HAM-D scores decreased steadily from 20.58 at baseline to 12.07 at week 26 and to 11.18 at week 52. Mean CGI scores decreased from 3.99 to 2.20 at week 26 and 2.19 at week 52. Therefore, St. John's wort extract ZE 117 is a safe and effective way to treat mild to moderate depression over long periods of time, and therefore seems especially suitable for a relapse prevention.
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Herbal drug treatment has been known for centuries as a part of traditional medicine. Nowadays, it is still considered a useful and natural way to treat several medical conditions, including mental disturbances. The most frequently treated mental conditions include mood disorders (mainly depression), anxiety disorders, somatoform disorders, age-related cognitive decline, and sometimes psychotic disorders. Some herbal formulations, such as St. John's wort, have been analyzed in clinical trials to estimate their real value. The use of other herbal medicines, such as Kava-kava, valerian, and Ginkgo biloba is discussed.
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The efficacy and safety of Hypericum extract WS 5570 in preventing relapse during 6 months' continuation treatment and 12 months' long-term maintenance treatment after recovery from an episode of recurrent depression were investigated in a double-blind, placebo controlled multicenter trial. Adult out-patients with a recurrent episode of moderate major depression, a 17-item Hamilton Depression Rating Scale (HAMD) total score > or =20 and > or =3 previous episodes in 5 years participated. After 6 weeks of single-blind treatment with 3 x 300 mg/day WS 5570 patients with score < or =2 on item 'Improvement' of the Clinical Global Impressions (CGI) scale and a HAMD total score decrease > or =50% versus baseline were randomized to 3 x 300 mg/day WS 5570 or placebo for 26 weeks. 426 patients were evaluated for efficacy. Relapse rates during continuation treatment were 51/282 (18.1%) for WS 5570 and 37/144 (25.7%) for placebo. Average time to relapse was 177+/-2.8 and 163+/-4.4 days for WS 5570 and placebo, respectively (time-to-event analysis; p=0.034; alpha=0.025 one-sided). Patients treated with WS 5570 showed more favorable HAMD and Beck Depression Inventory time courses and greater over-all improvement (CGI) than those randomized to placebo. In long-term maintenance treatment a pronounced prophylactic effect of WS 5570 was observed in patients with an early onset of depression as well as in those with a high degree of chronicity. Adverse event rates under WS 5570 were comparable to placebo. WS 5570 showed a beneficial effect in preventing relapse after recovery from acute depression. Tolerability in continuation and long-term maintenance treatment was on the placebo level.
Article
Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs). This study compared hypericum and the SSRI sertraline in the treatment of depression. In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks. The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size. The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.
Article
Extracts of St. John's wort have been widely used in the treatment of depression. Our aim was to review information related to the efficacy and safety of St. John's wort as an antidepressant. Primary and review articles were identified by a search of Medline (1960 to February 2000) and through secondary sources. All the articles identified from the data sources were evaluated and all relevant information was included in this review. The pharmacokinetics, mechanism of action, efficacy, side effects and drug interactions of St. John's wort have been examined in various studies. St. John's wort is a promising investigational antidepressant, but the data are not yet sufficient to accept hypericum as a first line antidepressant preparation for treatment of depression. Besides the need for dose standardization and adequate trial lengths, there is a need for studies in severely depressed patients and long-term studies to assess the risk of relapse and recurrence.
Article
Depression is a common condition in the community with a significant impact on affected individuals, their relatives and society. Many patients with depression do not seek treatment and are often concerned about the possible adverse effects of antidepressant drugs. Extract of Hypericum perforatum (St. John's wort) has long been recognized as a treatment for depression. Several published trials and meta-analyses have demonstrated the efficacy and tolerability of Hypericum extract for mild to moderate depression. Recent comparative trials of Hypericum extract and other antidepressants, including selective serotonin reuptake inhibitors (SSRIs), provide support for Hypericum extract efficacy. However, since the constituents of Hypericum extract differ between the individual manufacturers, the efficacy cannot be extrapolated from one extract to another. In this review, WS 5572, LI 160, WS 5570 and ZE 117 Hypericum extracts have been shown to be significantly more effective than placebo with at least similar efficacy and better tolerability compared to standard antidepressant drugs.
Chapter
This chapter focuses on CAM treatments supported by scientific evidence for mechanisms of action, clinical trials demonstrating safety and efficacy, and observations of benefit from the authors' clinical experience. There is limited data in some case, but this should not deter physicians from considering these substances when appropriate. There are six sections in the chapter: (1) Mood disorders; (2) Anxiety and stress-related disorders; (3) Substance abuse; (4) Hormone-related disorders; (5) Disorders of attention, memory, and cognition; and (6) Issues of quality control, product variability, side effects, drug interactions, and legal-ethical issues.
Analyses of juvenile depression studies with long established anti-depressants (tricyclic anti-depressants) have revealed discouragingly little benefit, while side effects have been profound. Modern anti-depressants like selective serotonin reuptake inhibitors seemed to solve part of this problem until they were found to be associated with an increased risk of suicidal attempts and ideation, hostile behaviour and self-harm, while meta-analyses have revealed only marginal therapeutic effects for the majority. Actually, no drug is unequivocally accepted as the gold-standard for young depressive patients. St. John's Wort (SJW) has been traditionally used in Europe to treat symptoms associated with juvenile depression. Close to 50 clinical studies performed over the last two decades have been presented as evidence that standardized SJW preparations are equally effective as synthetic anti-depressants in the treatment of mild to moderate depression in adults. Tolerability is excellent, but some relevant drug interactions have to be considered. Today, SJW is by far the most frequently prescribed medication for child and adolescent depression in Germany. Some pilot and observational studies from Germany, Canada and the US have delivered promising results. However, randomised controlled trials amongst this age group have yet to be carried out and are long overdue.
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Systematic reviews are considered the most reliable tool to summarize existing evidence. To determine whether reviews that address the same questions can produce different answers we examined systematic reviews of herbal medicine, homeopathy, and acupuncture taken from a previously established database. Information on literature searching, inclusion criteria, selection process, quality assessment, data extraction, methods to summarize primary studies, number of included studies, results and conclusions was compared qualitatively. Seventeen topics (eight on acupuncture, six on herbal medicines, three on homeopathy) had been addressed by 2–5 systematic reviews each. The number of primary studies in the reviews varied greatly within most topics. The most obvious reason for discrepancies between the samples was different inclusion criteria (in thirteen topics). Methods of literature searching may have contributed with some topics but the equivalence of the searches was difficult to assess. Differences were frequently observed in other methodological aspects, in results and in conclusions. This analysis shows that, at least in the three areas examined, systematic reviews often differ considerably. Readers should be aware that apparently minor decisions in the review process can have major impact.
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The cultivation of aromatic and medicinal plants for their direct as well as indirect uses is a common practice from ancient time. There are several medicinal plants which have not only the tolerance ability against the environmental contaminants but also may extract them from the polluted sites. Essential oil-bearing crops like peppermint (Mentha sps.), tulsi (Ocimum basilicum L.), industrial hemp (Cannabis sativa L.), Cymbopogon citratus etc., have been found to bear substantial efficiency to accumulate toxic metals e.g., Cd, As, Ni, Cu, Fe, etc. Generally the process used to extract the essential oil is steam distillation which has the least chance to allow the contaminants to move in oil. After harvesting the oil, residual biomass may be utilized for energy production. This energy may be produced by direct burning of biomass or production of biogas through the gasification of biomass. This integrated approach will not only reduce the cost of petroleum oil but also will help to develop a sustainable model which will help in mitigation of many environmental issues like reduction of greenhouse gases, pollution alleviation etc.
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Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential. We quantitatively reviewed the pre-clinical literature to examine if there is a cognitive-enhancing effect of H. perforatum in healthy rodents. Additionally, within these studies, we compared the effects observed in intact rodents versus those whose performance has been impaired, mostly through stress manipulations. The meta-analysis incorporated studies that examined the effect of H. perforatum versus placebo on memory indices of task performance. All analyses were based on weighting different studies according to their inverse variance. Thirteen independent studies (published 2000–2014) involving 20 experimental comparisons met our inclusion criteria. The results showed a large positive effect of H. perforatum on cognitive performance for intact, healthy rodents (d = 1.11), though a larger effect emerged for stress-impaired rodents (d = 3.10 for restraint stress). The positive effect on intact rodents was observed in tasks assessing reference memory as well as working memory, and was not moderated by the type of memory or motivation (appetitive versus aversive). Thus, while primarily considered as a medication for depression, H. perforatum shows considerable nootropic potential in rodents.
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Purveyors of ‘snake oil’ that was claimed to cure everything from baldness to impotence were familiar in the nineteenth century. In the twenty-first century, snake oil purveyors have been replaced by advocates of a variety of alternative therapies from homeopathy to reflexology and from acupuncture to chiropractic treatment, with their exaggerated claims about the effectiveness of their proposed treatment being largely based on flawed clinical trial results. Where well-designed and performed randomized clinical trials have been performed, the claimed effectiveness of the majority of alternative treatments has most often been shown to be a myth.
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Präparate auf der Basis von Hypericum-Extrakt gehören in Europa seit Jahren zu den am häufigsten verschriebenen Medikamenten bei Depressionen und gewinnen in dieser Indikation neuerdings auch in den USA zunehmend an Therapiebedeutung. Die Wirksamkeit von Hypericum-Extrakt-Präparaten bei leichten bis mittelschweren depressiven Episoden wurde in randomisierten Doppelblindstudien gegen Placebo und gegen synthetische Antidepressiva (z.B. Imipramin, Fluoxetin) belegt [13, 15, 21]. In aktiv-kontrollierten Studien wurde dabei neben der vergleichbaren Wirksamkeit auf die bessere Verträglichkeit von Hypericum-Präparaten hingewiesen [3–5, 13].
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Background: Premenstrual syndrome (PMS) is a common condition. Some of the most widely prescribed medications are selective serotonin reuptake inhibitors (SSRIs), based on the hypothesized role of serotonin in the production of PMS symptoms. PMS sufferers, especially those experiencing mild to moderate symptoms, are often reluctant to take this form of medication and instead buy over-the-counter preparations to treat their symptoms, for which the evidence base with regard to efficacy is limited. Hypericum perforatum (St John's wort) influences the serotonergic system. As such, this widely available herbal remedy deserves attention as a PMS treatment. Objective: To investigate the effectiveness of Hypericum perforatum on symptoms of PMS. Study design: This randomized, double-blind, placebo-controlled, crossover study was conducted between November 2005 and June 2007. Setting: Institute of Psychological Sciences, University of Leeds, Leeds, UK. Participants: 36 women aged 18-45 years with regular menstrual cycles (25-35 days), who were prospectively diagnosed with mild PMS. Intervention: Women who remained eligible after three screening cycles (n = 36) underwent a two-cycle placebo run-in phase. They were then randomly assigned to receive Hypericum perforatum tablets 900 mg/day (standardized to 0.18% hypericin; 3.38% hyperforin) or identical placebo tablets for two menstrual cycles. After a placebo-treated washout cycle, the women crossed over to receive placebo or Hypericum perforatum for two additional cycles. Main outcome measures: Symptoms were rated daily throughout the trial using the Daily Symptom Report. Secondary outcome measures were the State Anxiety Inventory, Beck Depression Inventory, Aggression Questionnaire and Barratt Impulsiveness Scale. Plasma hormone (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol, progesterone, prolactin and testosterone) and cytokine (interleukin [[IL]-1 beta, IL-6, IL-8, interferon [IFN]-gamma and tumour necrosis factor [TNF]-alpha) levels were measured in the follicular and luteal phases during Hypericum perforatum and placebo treatment. Results: Hypericum perforatum was statistically superior to placebo in improving physical and behavioural symptoms of PMS (p < 0.05). There were no significant effects of Hypericum perforatum compared with placebo treatment for mood- and pain-related PMS symptoms (p>0.05). Plasma hormone (FSH, LH, estradiol, progesterone, prolactin and testosterone) and cytokine (IL-1 beta, IL-6, IL-8, IFN gamma and TNF alpha) levels, and weekly reports of anxiety, depression, aggression and impulsivity, also did not differ significantly during the Hypericum perforatum and placebo cycles (p > 0.05). Conclusion: Daily treatment with Hypericum perforatum was more effective than placebo treatment for the most common physical and behavioural symptoms associated with PMS. As proinflammatory cytokine levels did not differ significantly between Hypericum perforatum and placebo treatment, these beneficial effects are unlikely to be produced through this mechanism of action alone. Further work is needed to determine whether pain- and mood-related PMS symptoms benefit from longer treatment duration.
Article
St. John's Wort (Hypericum perforatum) is a perennial herb distributed in temperate and subtropical regions of the world. It proved to be a useful medicinal herb for its antidepressant (for mild to moderate depression), anti-inflammatory and antiviral properties'. Hypericin and hyperforin are the key chemical components in the plant. However, opinions differ as to the active constituent(s) attributable to antidepressant properties. The present investigation aims at in vitro establishment and long-term maintenance of callus and regeneration of Hypericum perforatum for eventual commercial exploitation of its important bioactive compounds. Successful induction of callus has been achieved in Murashige and Skoog (MS) medium. The studies showed that fully defined MS media in combination with benzyl adenine (BA) (0.1%) and 2,4-dichlorophenoxy acetic acid (2,4-D) (0.05%) was effective for both initiation and sustained growth of callus tissue. The process of subsequent subculturing of calli led to the complete regeneration of plant showing a rapid and vigorous growth. Plants with vigorous leaf and root growth were obtained after they were subcultured into MS media with growth hormones, BA (0.5 mg/l) and kinetin (1 mg/l).
Article
This book is intended for students and professionals who are seeking an up-to-date summary of research-based information on depression. Chapters cover clinical and diagnostic information, as well as features of the course of depression and the demographic features of the disorder. For example, topics include the considerable impairment associated with depression (it isn't 'all in your mind') and discussion of why depression is particularly common in women and the young.
Article
Objective The objective of this article is to review the current knowledge of the pharmacology, sites of action, and therapeutic effectiveness of St. John's Wort. Method The method used was a review of the available literature, using keywords to search the medline database. Bibliographies of the papers, thus obtained, were searched for further documents not referenced by medline. We reviewed papers from this collection. Results This review reveals that most of the available data on efficacy and safety of St. John's Wort involve its use in mild to moderate depression. Much, but not all of the prevailing opinion is positive. Nevertheless, the quality of therapeutic trials vary so greatly that definitive conclusions are not possible. Both the source and mode of St. John's Wort's therapeutic effect are unclear. We need further controlled studies of effectiveness, safety, and mode of action. In addition to its use in depression, there are reports suggesting possible therapeutic effects in other conditions such as certain malignancies and infections, but these are far too preliminary to permit any conclusions.
Article
A massive, systemic, and yet largely silent revolution is occurring in mental health today and is gathering steam for tomorrow: self-help efforts without professional intervention. The self-help revolution traverses multiple disciplines and entails diverse activities. In this article, the author briefly traces the reasons for this self-help revolution and, more urgently, argues for organized psychology's vital involvement in it. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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Over the years, research on antioxidants and medicinal plants has gained enormous popularity and emerged as a potential therapeutic to prevent free radical generated damage in the human body. Free radicals are well known for the pathogenesis of various degenerative diseases,. i.e., cancer, cardiovascular diseases, immunomodulator, neurological disorder, diabetes, aging, etc. Medicinal plants are being viewed as easily available and potent source of antioxidants as they contain a mixture of different chemical compounds that may act individually or in synergy to cure the disease and improve health. A single plant may have diversity of phytochemicals, which represents a number of pharmacological properties. However, many herbal medicine used today have not gone under careful scientific assessment and some have the potential to cause serious toxic effects. Therefore, careful scientific and clinical studies of the herbal medicine for the safety and toxicity are required. With high prevalence of medicinal plants in India and their potential as a source of antioxidants need to be judiciously investigated. The present chapter focuses on the role of antioxidants in disease prevention and their potential in Indian medicinal plants.
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Against the background of proven efficacy in mild to moderate depressive disorders and an excellent tolerability profile in monotherapy, there is sufficient evidence from interaction studies and case reports to suggest that St John’s wort may induce the cytochrome P450 (CYP) 3A4 enzyme system and the P-glycoprotein drug transporter in a clinically relevant manner, thereby reducing efficacy of co-medications. Drugs most prominently affected and contraindicated for concomitant use with St John’s wort are metabolised via both CYP3A4 and P-glycoprotein pathways, including HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors (only CYP3A4), the immunosuppressants ciclosporin and tacrolimus, and the antineoplastic agents irinotecan and imatinib mesylate. Efficacy of hormonal contraceptives may be impaired as reflected by case reports of irregular bleedings and unwanted pregnancies. Drugs with a narrow therapeutic index should be monitored more closely when St John’s wort is added, discontinued or the dosage is changed. The St John’s wort constituent hyperforin is probably responsible for CYP3A4 induction via activation of a nuclear steroid/pregnane and xenobiotic receptor (SXR/PXR) and hypericin may be assumed to be the P-glycoprotein inducing compound, although the available evidence is less convincing. Combinations of St John’s wort with serotonergic agents and other antidepressants should be restricted to prescription-only, by experienced clinicians, due to potential central pharmacodynamic interactions. In conclusion, providing certain precautions and contraindications are followed, and adequate information is given to healthcare professionals and patients, the safe and effective use of quality-tested St John’s wort products can be ensured.
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As more and more people are using unregulated herbaceuticals worldwide, counselors need to be alert to the types of herbs clients may be taking; the effects, side effects, and drug interactions associated with different herbaceuticals; and the ethical implications of treating a client who is taking herbaceuticals. This article provides an overview of the psychological, physiological, cultural, and legal issues associated with herbaceuticals and introduces some of the emerging ethical issues.
Article
Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.
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An analytical‐scale method using supercritical carbon dioxide for extraction of flavonoidal compounds from Hyperici herba has been developed. Carbon dioxide pressure, temperature, flow, percentage of methanol as organic modifier, and trapping conditions were optimized using an experimental design. Quercetin and rutin were the compounds detected in the HPLC chromatogram of each extract. Recovery and the reproducibility of both compounds were calculated. Under optimized conditions recovery was estimated to be 92% and 76% for quercetin and rutin, respectively, with RSD values equal to 6.4% and 5.2%. Results from the supercritical fluid extraction method were compared with results obtained via a sonication method, using a methanol–water extraction system.
Article
Systematic reviews have considerable impact on the discussion of complementary therapies in the scientific community, in the media and on healthcare decision making, because they are considered to be the most reliable tool to summarize and assess the evidence available on a defined question. This article aims to discuss some of the most relevant problems of systematic reviews, both in general and in relation to complementary and alternative medicine (CAM). Review questions in CAM, for example, tend to be broad which often leave the results open to subjective interpretation. To search the literature comprehensively, it is sometimes necessary to go beyond conventional electronic databases, but the quality of the material identified in other sources is often doubtful. Small changes in selection criteria can strongly influence the inclusion of studies. Publication bias, insufficient reporting in primary studies, and problems with quality assessment are relevant to both conventional medicine and CAM. While systematic reviews are, for the time being, without alternative, they have to be read and interpreted with caution. In many cases, particularly in the area of CAM, they will leave room for controversial discussions.
Article
• The evidence base for the use of dietary supplements is well documented for some, such as the essential nutrients, but it is scant for others, such as some designer supplements and botanicals. • Popular dietary supplements consumed by older Americans that have national public health recommendations and established guidelines for use include omega-3 fatty acids; the B vitamins, folic acid, vitamins B6, and B12; vitamins D and E; and the minerals, calcium, potassium, and magnesium. • Dietary supplements not endorsed by national public health recommendations but with a considerable evidence base upon which randomized clinical trials can be planned or guidelines for use might be formulated include coenzyme Q10, creatine, and the botanicals black cohosh, French pine bark, Ginkgo biloba, and saw palmetto. • A clinical deficiency of vitamins or minerals, other than iron and possibly vitamin D, is uncommon in the United States, except for certain high-risk groups. • In situations when recommended nutrients cannot be obtained by food alone or retained by the body because of impaired absorption or other physiologic limitations, dietary supplements can provide benefit. When taken, multivitamin preparations should include 100% of the daily value for vitamins B12, B6, D, and folic acid.
Article
Reviews the available data on hypericum perforatum, an herbal remedy known as St. John's wort commonly used for psychological and psychiatric symptoms, such as anxiety, depression, cognitive dulling, and insomnia. Specifically, data regarding hypericum's efficacy, tolerability, and potential for interactions is examined. It is hoped that this review will allow clinicians to draw their own conclusions regarding this herb and provide them with information for educating and guiding discussions with patients. It is noted that the ethical, legal, and practice issues related to psychologists recommending—or even discussing—the use of herbal preparations remain complex, and that psychologists should be aware that this is not a risk-free area. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
There is a moderate amount of evidence to suggest that St John's wort is better than placebo in the short-term management of mild to moderate depressive illness, but there is increasing concern over reports of drug interactions. This article examines the scientific evidence and discusses relevant clinical issues.
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A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990. To document trends in alternative medicine use in the United States between 1990 and 1997. Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively. A total of 1539 adults in 1991 and 2055 in 1997. Prevalence, estimated costs, and disclosure of alternative therapies to physicians. Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P < or = .001). The therapies increasing the most included herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P = .002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services. Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.
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To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. Systematic review and meta-analysis of trials revealed by searches. TRIALS: 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed.
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The aim of this research was to study the relationship between the clinical interview skills of primary care physicians and their psychodiagnostic ability during office visits. Ten doctors took part in the study, and 233 patients were assessed. The patients were seen and diagnosed by their physicians and interviewed afterward by a psychiatrist using the Present State Examination. All the interviews with the primary care physicians were recorded on videotape, and the Physician's Skills Observation Scale was used to analyze 10 interviews per doctor, five psychiatric cases and five nonpsychiatric cases. The physician's active listening (eye contact, posture, and absence of verbal interruptions) and ability to ask questions with psychological content were associated with the ability to identify the patient's emotional problems. This association was shown to be independent of the physician's characteristics (social, academic, attitudinal, and professional), the sociodemographic characteristics of the patients, the time spent in exploration during the office visit, and the severity of the emotional or somatic disorder. The findings of this research highlight the need to train primary care physicians in specific interview skills, in order to improve their ability to identify mental disorders in their practices.
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The German Ministry of Health commissioned a nonprofit organization to develop a tool for assessing the quality of psychiatric hospital care. The authors were members of an expert group established to develop an assessment tool that could be used by professional caregivers, patients, patients' relatives, managers, purchasers, and mental health care planners. A three-dimensional model was developed in which 23 quality standards may be applied to 28 areas of practice. For each application, questions can be asked at four levels to stimulate ongoing quality management: the individual treatment process, the individual outcome, the treatment unit, and the hospital as a whole. The authors provide sample questions to illustrate the approach. The approach to quality assessment embodied in the model is comprehensive and addresses ethical issues, but it is also complicated and difficult to handle. Unlike models developed in the United States, it is not intended to be objective or standardized, and it does not yield a score. To some extent, the model's approach to assessment may reflect German cultural values and traditions.
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• Previous studies of medical outpatients have documented a high prevalence of depression that is often unrecognized by primary physicians. However, the subjective methodologies of most of these studies limit their quantitative and comparative usefulness. By contrast, in the present study, 526 medical outpatients completed a self-report questionnaire, the Beck Depression Inventory (BDI). Questionnaire results were calibrated by psychiatric interviews of a subsample of 41 patients. The prevalence of depression was 12.2% when at least mild depression was used as a criterion; the rate for moderate depression was 5.5%, and the rate for severe, probably "psychotic," depression was 0.6%. A review of medical charts showed that primary physicians failed to diagnose about 50% of both depressed and otherwise impaired patients. The BDI was shown to be a sensitive screening test; its use is advocated to improve recognition of depression by primary physicians.
Article
In a double-blind, placebo controlled clinical trial, the efficacy and tolerance of 8 weeks' treatment with Neurapas® tablets for moderate to severe depressive symptoms was investigated in 30 patients per group. The basic parameters from the doctor's and patients' assessments of therapeutic progress were used for the purposes of analysis. Tolerance was determined on the basis of adverse drug reactions (ADRs), dose changes and drop-outs as well as general clinical findings, the vital parameters blood pressure and pulse and laboratory tests.
Article
An empirical evaluation of meta-analytic procedures, defining results of individual studies, effect size and statistical significance, a framework for meta-analytic procedures, comparing and combining studies, the file drawer problem, the evaluation of effect sizes, the issue of study quality, a summarizing example.
Article
This is an account of further work on a rating scale for depressive states, including a detailed discussion on the general problems of comparing successive samples from a ‘population’, the meaning of factor scores, and the other results obtained. The intercorrelation matrix of the items of the scale has been factor-analysed by the method of principal components, which were then given a Varimax rotation. Weights are given for calculating factor scores, both for rotated as well as unrotated factors. The data for 152 men and 120 women having been kept separate, it is possible to compare the two sets of results. The method of using the rating scale is described in detail in relation to the individual items.
Article
The bicaudate and bifrontal indices have been used in prior computed tomographic studies to investigate atrophy of the caudate nuclei in patients with Huntington's chorea and cerebral atrophy. However, the relationship between these indices and caudate volume has not been documented previously. In this study, we used high-field magnetic resonance imaging (MRI) to determine the effects of normal aging on the bicaudate and bifrontal indices and to study the relationship between these indices and caudate volume. The subjects were 49 normal volunteers, aged 22 to 82 years, who were without any significant neurologic or psychiatric disorders. Age was positively correlated with bicaudate index ( r = .59; P < .0001) and bifrontal index ( r = .40; P < .0047). Age was negatively correlated with caudate nuclei volume ( r = -.47; P < .0005). Caudate volume was negatively correlated with bicaudate ( r = -.27; P < .06) and bifrontal ( r = -.31; P < .03) indices. These findings are consistent with prior reports of caudate nuclei degeneration with increasing age. Linear and volumetric caudate measurements with MRI may prove useful in the investigation of caudate nuclei function in the neuromotor decline with normal aging and in disorders such as Huntington's chorea.
Article
A randomized, double-blind study examining the effectiveness and tolerance of a standardized hypericum preparation when compared to maprotiline was performed in a group of 102 patients with depression, in accordance with ICD-10, F 32.1. The study was conducted in the offices of neurology and psychiatry specialists. The patients received, over a period of 4 weeks, either 3 x 300 mg of the hypericum extract or 3 x 25 mg maprotiline pills of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI). The total score of the HAMD scale dropped during the 4 weeks of therapy in both treatment groups by about 50%. The mean values of the D-S scale and the CGI scale showed similar results, and after 4 weeks of therapy, no significant differences in either treatment group were noticed. The onset of the effects occurred up to the second week of treatment, but were observed earlier with maprotiline than with the hypericum extract. On the other hand, maprotiline treatment resulted in more cases of tiredness, mouth dryness, and heart complaints.
Article
Effective, economical, and reliable means of screening subjects for cognitive impairment when personal contact is not feasible could facilitate epidemiologic studies and longitudinal assessment. The Short Portable Mental Status Questionnaire (SPMSQ) is a 10-item examination that has been found reliable and valid in distinguishing demented subjects from cognitively intact subjects when given face to face. The current study assessed the utility of a telephone version of the SPMSQ in patients evaluated in an outpatient geriatric assessment program. Mean scores for both test versions decreased with dementia severity and correlated significantly. Mean score differences between the two versions were not affected by reports of hearing impairment or the time interval between test administration. Both test versions correlated significantly with the Mini-Mental State Examination. In distinguishing demented “from nondemented subjects, sensitivity and specificity were .74 and .79 for the telephone test and .74 and .91 for the face-to-face test, respectively.
Article
Seventy-two depressive patients of 11 physicians' practices were treated in a double-blind study for a period of 6 weeks either with hypericum extract LI 160 or with placebo. Inclusion criterion was a major depression in accordance with DSM-III-R. The changes were assessed using four psychometric scales (HAMD, D-S, BEB, CGI). After 4 weeks of therapy, the statistical evaluation revealed a significant improvement in all four psychometric tests in the active group as compared to the placebo group. After switching the placebo group to active treatment (5th to 6th week of therapy), significant improvements were found in the original placebo group. No serious side effects were observed.
Article
This article presents a meta-analysis of the literature on stress and immunity in humans. The primary analyses include all relevant studies irrespective of the measure or manipulation of stress. The results of these analyses show substantial evidence for a relation between stress and decreases in functional immune measures (proliferative response to mitogens and natural killer cell activity). Stress is also related to numbers and percent of circulating white blood cells, immunoglobulin levels, and antibody titers to herpesviruses. Subsequent analyses suggest that objective stressful events are related to larger immune changes than subjective self-reports of stress, that immune response varies with stressor duration, and that interpersonal events are related to different immune outcomes than nonsocial events. We discuss the way neuroendocrine mechanisms and health practices might explain immune alteration following stress, and outline issues that need to be investigated in this area.
Article
Up to now, the antidepressant efficacy of the extract of St. John's wort, LI 160, has been compared to imipramine and maprotiline, demonstrating similar antidepressant efficacy in mildly to moderately depressed patients, treated either with LI 160 or the respective synthetic comparator. In the study reported here, LI 160 (total daily dose: 900 mg) was compared with the sedating tricyclic amitriptyline (total daily dose: 75 mg) in a controlled, randomized, multicentre trial. At the end of the 6-week study, the major target variable, the Hamilton Depression Scale response rate, exhibited no statistically significant difference between the groups, although a tendency for a better response rate was seen in the amitriptyline group. The secondary efficacy parameters, decreases in the total Hamilton Depression and Montgomery-Asberg scores, showed a significant advantage for amitriptyline, but only at week 6. With regard to tolerability, LI 160 was clearly superior to amitriptyline, particularly in relation to anticholinergic and Central Nervous System adverse events. Thus, 37% of the LI 160 treated patients reported adverse events, compared to 64% in the amitriptyline group. This considerable superiority in tolerability for LI 160 in relation to amitriptyline, could confer an advantage in improving compliance for antidepressant pharmacotherapy.
Article
In Germany, hypericum extracts are among the most widely prescribed antidepressants. Additionally, many preparations of St. John's wort are sold on the free market and one extract is even the best selling antidepressant in the country. In contrast to synthetic antidepressants, the approval procedures are not so strict, which implies that the pharmaceutical industry is not forced to conduct clinical trials suitable for licensing. Nevertheless, numerous studies on hypericum extracts including depressed patients have been published in the last 20 years. The purpose of this paper is to review these investigations in respect of methodological considerations and to draw conclusions pertaining to the proof of antidepressant efficacy. To this effect, a computer-assisted literature research was performed and manufacturers were asked to supply the author with study results. A total of 12 placebo-controlled trials with hypericum extracts were performed, mostly with positive results. Also in comparison with synthetic antidepressants (3 studies published), a similar reduction of depressive symptomatology was seen, although the comparators were not adequately dosed. No trials in severely depressed patients have been published yet. Since most studies on hypericum have methodological flaws, further studies are warranted.
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