hypericum and Depressive-Disorder

Depression is the most common mental disorder, affecting about 3.8% of the population worldwide. Clinical symptoms of depression include sadness, anxiety and frequent mood swings, among others. Selective serotonin reuptake inhibitors (SSRIs), psychotherapy and behavioral therapy are commonly used for the treatment of this condition. Since SSRIs are associated with various side effects, extract of St. John's wort (SJW) has been suggested as an effective alternative. However, there are conflicting studies regarding its efficacy. Many studies have reported positive outcomes with low adverse effects, while others did not find it to be a suitable alternative.. To analyze the available studies using SJW for depression therapy and to thoroughly evaluate its effectiveness compared to SSRIs and placebo.. Relevant articles for our meta-analysis were found using Medline (via PubMed), Cinahl (via EBSCO), Scopus, and Web of Sciences databases. Studies were included as per the predefined Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria. A demographic summary of the patients treated with either SJW, placebo or SSRIs was collected and Hamilton Depression Rating Scale (HAMD) scores were extracted. Risks of bias analysis, diagnostic odds ratio (OR), risk ratio (RR), and sensitivity calculation were evaluated using Revman software, and the publication bias was assessed using MedCalc software.. Fourteen clinical trials with a total of 2270 depression patients were included in accordance with the inclusion criteria. All analyzed papers were published between 2000 and 2022. For patients treated with either SSRIs or SJW, a pooled OR of 2.44 with a 95% confidence interval (95% CI) of 1.33-4.45 was obtained. The data were heterogeneous, with a tau2 value of 0.54, χ2 value of 31.05, degrees of freedom (df) value of 7, I2 value of 77%, and an overall Z-value of 2.90 with p = 0.004.. Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications.

Topics: Adult; Depression; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors

Depression is a mental health disorder that develops as a result of complex psycho-neuro-immuno-endocrinological disturbances. This disease presents with mood disturbances, persistent sadness, loss of interest and impaired cognition, which causes distress to the patient and significantly affects the ability to function and have a satisfying family, social and professional life. Depression requires comprehensive management, including pharmacological treatment. Because pharmacotherapy of depression is a long-term process associated with the risk of numerous adverse drug effects, much attention is paid to alternative therapy methods, including phytopharmacotherapy, especially in treating mild or moderate depression. Preclinical studies and previous clinical studies confirm the antidepressant activity of active compounds in plants, such as St. John's wort, saffron crocus, lemon balm and lavender, or less known in European ethnopharmacology, roseroot, ginkgo, Korean ginseng, borage, brahmi, mimosa tree and magnolia bark. The active compounds in these plants exert antidepressive effects in similar mechanisms to those found in synthetic antidepressants. The description of phytopharmacodynamics includes inhibiting monoamine reuptake and monoamine oxidase activity and complex, agonistic or antagonistic effects on multiple central nervous system (CNS) receptors. Moreover, it is noteworthy that the anti-inflammatory effect is also important to the antidepressant activity of the plants mentioned above in light of the hypothesis that immunological disorders of the CNS are a significant pathogenetic factor of depression. This narrative review results from a traditional, non-systematic literature review. It briefly discusses the pathophysiology, symptomatology and treatment of depression, with a particular focus on the role of phytopharmacology in its treatment. It provides the mechanisms of action revealed in experimental studies of active ingredients isolated from herbal antidepressants and presents the results of selected clinical studies confirming their antidepressant effectiveness.

Topics: Antidepressive Agents; Depression; Depressive Disorder; Humans; Hypericum; Phytotherapy

As clinical practice guidelines vary widely in their search strategies and recommendations of complementary and alternative medicine (CAM) for depression, this overview aimed at systematically summarising the level 1 evidence on CAM for patients with a clinical diagnosis of depression.. PubMed, PsycInfo and Central were searched for meta-analyses of randomised controlled clinical trials (RCTs) until 30 June 2018. Outcomes included depression severity, response, remission, relapse and adverse events. The quality of evidence was assessed according to Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) considering the methodological quality of the RCTs and meta-analyses, inconsistency, indirectness, imprecision of the evidence and the potential risk of publication bias.. The literature search revealed 26 meta-analyses conducted between 2002 and 2018 on 1-49 RCTs in major, minor and seasonal depression. In patients with mild to moderate major depression, moderate quality evidence suggested the efficacy of St. John's wort towards placebo and its comparative effectiveness towards standard antidepressants for the treatment for depression severity and response rates, while St. John's wort caused significant less adverse events. In patients with recurrent major depression, moderate quality evidence showed that mindfulness-based cognitive therapy was superior to standard antidepressant drug treatment for the prevention of depression relapse. Other CAM evidence was considered as having low or very low quality.. The effects of all but two CAM treatments found in studies on clinical depressed patients based on low to very low quality of evidence. The evidence has to be downgraded mostly due to avoidable methodological flaws of both the original RCTs and meta-analyses not following the Consolidated Standards of Reporting Trials and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Further research is needed.

Topics: Acupuncture Therapy; Antidepressive Agents; Cognitive Behavioral Therapy; Complementary Therapies; Crocus; Curcumin; Dance Therapy; Depressive Disorder; Depressive Disorder, Major; Dietary Supplements; Drugs, Chinese Herbal; Fatty Acids, Omega-3; Humans; Hypericum; Meta-Analysis as Topic; Mindfulness; Music Therapy; Phototherapy; Plant Preparations; Qigong; S-Adenosylmethionine; Systematic Reviews as Topic; Tai Ji; Trace Elements; Vitamins; Yoga; Zinc

Herbal products are popular among women during the perinatal period. St John's wort (SJW), Hypericum perforatum, is a common remedy for mild depression, a problem prevalent in this population. Although the safety of herbal products must be investigated, ethical issues constrain intervention studies in humans. Hence, animal studies often inform clinical decisions. The objective of this study is to systematically review rodent studies assessing the safety of SJW during the perinatal period. A literature search to November 10, 2017, identified 10 rodent studies that met a priori inclusion criteria. Study quality was evaluated according to both the Systematic Review Centre for Laboratory animal Experimentation tool for assessing bias and recommendations for appropriate reporting of herbal medicine research. Significant methodological limitations were found in each of the studies reviewed. These limitations include the lack of botanical verification and omission of extract characterization, inadequate explanation of dosage rationale, and absence of bias limiting protocols. Critical appraisal with contemporary tools indicates that each of the reviewed studies lacks appropriate rigour, rendering the results unreliable. Despite this, these papers are used in the rationale for recommending or contraindicating SJW during pregnancy and lactation.

Topics: Animals; Depressive Disorder; Female; Hypericum; Lactation; Mice; Phytotherapy; Plant Preparations; Pregnancy; Rats; Research Design

WS(®) 5570 is a Hypericum (St. John's wort) dry extract that is available as a medicinal product in coated tablets and has a marketing authorisation for the acute treatment of mild to moderate major depression in Germany.. This article summarizes the current state of knowledge regarding the clinical efficacy and safety of WS(®) 5570.. In randomised, double-blind, controlled clinical trials the antidepressant effect of the drug was superior to that of the placebo and at least comparable to that of paroxetine. The beneficial effect of WS(®) 5570 is particularly pronounced with respect to the core symptoms of depression. There is evidence that the drug may also be effective in moderate to severe depression and in prophylactic continuation treatment after recovery from an acute episode.. WS(®) 5570 has a very favourable safety profile, with adverse event rates on one level with placebo and lower than that of synthetic antidepressants in randomised, controlled clinical trials. It may therefore also be an option for patients who do not tolerate other antidepressant drugs. Patients with polydrug treatment should nevertheless use the drug with caution, due to its potential for interactions.

Topics: Antidepressive Agents; Depressive Disorder; Double-Blind Method; Drug Interactions; Germany; Humans; Hypericum; Phytotherapy; Placebos; Plant Extracts; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome

A boxed-warning in antidepressant labeling now informs prescribers of the potential for treatment-emergent suicidality to occur. Consequently, alternative "natural" antidepressant therapies widely viewed to be devoid of this risk, such as St. John's wort (SJW) and s-adenosyl methionine (SAM-e), may experience a resurgence in popularity and expansion of use beyond mild forms of depressive illness. The purpose of this article is to critically assess whether the clinical evidence supports the use of SJW and SAM-e as alternatives to conventional antidepressants in the treatment of major depressive disorder (MDD). In addition, this article evaluates whether the behavioral adverse event profiles of SJW and SAM-e suggest an increased risk for suicidality, like their conventional counterparts.. A comprehensive literature review was performed (Jan 1975-July 2010) to identify all English language reports of placebo-controlled studies of SJW and SAM-e conducted for psychiatric indications. MDD studies were categorized as "positive" or "negative" based on statistical superiority to placebo on prospectively-defined, primary, clinician-rated efficacy parameters (e.g., change in Hamilton Depression scores [HAM-D] or Montgomery-Asberg Depression Rating Scale [MADRS] total). Treatment effect size (Cohen's d) was also calculated in each case to assess the clinical relevance of the findings. Behavioral-related adverse events were summarized by treatment.. Ten of 14 (71%) SJW studies in mild-to-moderate MDD were positive. The mean and median effect sizes for HAM-D change in those studies were 0.64 and 0.48, respectively, indicative of a moderately-large treatment effect. In the few studies that included patients with severe symptoms, however, or which evaluated long-term maintenance of effect, SJW did not differentiate from placebo. The majority of SAM-e studies in MDD were also positive (8/14, 57%); however, most were methodologically flawed to some extent. Based on the magnitude of the treatment-effect size in a number of positive studies, SJW appears to be useful for the short-term treatment of mild-to-moderate depressive illness in adults. Existing data do not support the use of SJW in more severely depressed individuals. The SAM-e clinical data also are strongly suggestive of antidepressant efficacy; however, until more rigorously generated data become available it is not possible to reach a more definitive conclusion. There are no long-term treatment data that convincingly demonstrate long-term maintenance of effect for either product. The reviewed studies did not reveal evidence of treatment-emergent suicidality, suggesting that this risk for either product is low. However, the studies examined were not prospectively designed to detect such events and therefore were likely unable to reliably assess this risk.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Humans; Hypericum; Phytotherapy; Psychiatric Status Rating Scales; S-Adenosylmethionine; Suicide Prevention; Treatment Outcome

To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references.. Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints.. Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located.. Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo.. A number of herbal medicines show promise in the management of mild-to-moderate depression.

Topics: Antidepressive Agents; Clinical Trials as Topic; Crocus; Depressive Disorder; Echium; Evidence-Based Medicine; Humans; Hypericum; Lavandula; Phytotherapy; Plants, Medicinal; Rhodiola

Complementary and alternative medicine (CAM) therapies are commonly practiced in the United States and are used more frequently among women than men. This article reviews several CAM treatments for depressive disorders in women, with a focus on major depressive disorder across the reproductive life cycle. The CAM therapies selected for this review (ie, S-adenosylmethionine, omega-3 fatty acids, St John's wort, bright light therapy, acupuncture, and exercise) were based on their prevalence of use and the availability of randomized, placebo-controlled data. Further study is necessary to delineate the role of specific CAM therapies in premenstrual syndrome, premenstrual dysphoric disorder, antepartum and postpartum depression, lactation, and the menopausal transition.

Topics: Acupuncture Therapy; Adult; Complementary Therapies; Depressive Disorder; Depressive Disorder, Major; Exercise Therapy; Fatty Acids, Omega-3; Female; Humans; Hypericum; Phototherapy; Phytotherapy; Plant Preparations; S-Adenosylmethionine; Sex Factors; Treatment Outcome; United States

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.

Topics: Animals; Antidepressive Agents; Clinical Trials as Topic; Depression; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Treatment Outcome

Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal.. An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events.. A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate.. Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.

Topics: Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Arginine; Depressive Disorder; Humans; Hypericum; Kava; Lysine; Magnesium; Passiflora; Phytotherapy; Randomized Controlled Trials as Topic; Vitamin B 6

The adoption of the EU community monograph on Hypericum constitutes a milestone in the process of harmonisation of herbal medicinal products within the European Community. The assessment of the published clinical data revealed that for two types of extracts the evidence of the efficacy in mild to moderate depressive episodes compared to placebo or standard medication was found to be acceptable. Additionally, a sufficient efficacy in relapse prophylaxis could be demonstrated for these two herbal preparations. For some other dry extracts, the efficacy in the short-term treatment of symptoms in mild depressive disorders was found to be substantiated. Short-term treatment with preparations containing low amounts of hyperforin did not increase cytochrome P450 enzyme activity. Therefore the oral administration of traditional herbal preparations is restricted to two weeks. In the case that an applicant demonstrates that the daily intake of hyperforin is below 1 mg the warnings on interactions may be omitted in traditional herbal medicinal products. Additionally the cutaneous administration of traditional liquid herbal preparations for the traditional use in symptomatic treatment of minor inflammations of the skin and as an aid in healing minor wounds was included in the monograph.

Topics: Clinical Trials as Topic; Depressive Disorder; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; European Union; Humans; Hypericum; Phytotherapy; Plant Extracts; Secondary Prevention

The use of Hypericum as an herbal medicine was first described in the time of Hippocrates and Hypericum has been used as an antidepressant since the 1500s. In the last 20 years, the use of Hypericum for treating depression has entered the arena of conventional medicine. In Germany, for example, Hypericum is prescribed four times as often as Prozac for depression. Many articles have been published on the efficacy and safety of Hypericum in treating mild to moderate depression, including a meta-analysis that was published in 2005 in the British Journal of Psychiatry. This meta-analysis summarized the results of 37 studies, that were conducted on 5,000 subjects, comparing Hypericum to placebo and other antidepressants. The authors of the meta-analysis concluded that Hypericum products are effective in the treatment of mild to moderate depression with fewer side effects compared to traditional antidepressants. In cases of severe depression, insufficient evidence was found of Hypericum's efficacy. The current review provides details of the results of the clinical trials on Hypericum that were published in 2005-2006, and presents information on the novel mechanism of action of Hypericum. The safety and possible drug interactions of Hypericum are also reviewed.

Topics: Clinical Trials as Topic; Depression; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts

This article aims to summarize the current state of knowledge on St. John's wort (Hypericum perforatum L.) which is one of the oldest and best investigated medicinal herbs. Dried alcoholic extracts are the most important preparations on the market although a variety of other preparations are available. Depressive disorders according to modern diagnostic standards are the best known and most widely investigated indication although the more traditional, broader indication of 'psycho-vegetative disorders, depressive disorders, anxiety and/or nervous agitation', including diagnoses such as somatoform disorders, might more adequately describe what Hypericum extracts are actually used for by many practitioners. The exact mechanisms of action are still unclear, but the available research clearly shows that various bioactive constituents contribute to the clinical effects reported, often in a synergistic manner. Hypericum extracts have consistently shown activity in pharmacological models related to antidepressant effects. Randomized clinical trials show that Hypericum extracts are more effective than placebo and similarly effective as standard antidepressants while having better tolerability in the acute treatment of major depressive episodes. The most important risk associated with Hypericum extracts are interactions with other drugs. Therefore, physicians need to be informed whether their patients take St. John's wort products. If the risk of interactions is adequately taken into account, high quality Hypericum extracts are an effective and safe tool in the hand of qualified health profession-als in primary care.

Topics: Antidepressive Agents; Depressive Disorder; Depressive Disorder, Major; Herb-Drug Interactions; Humans; Hypericum; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Risk Factors; Somatoform Disorders

In some countries extracts of the plant Hypericum perforatum L. (popularly called St. John's wort) are widely used for treating patients with depressive symptoms.. To investigate whether extracts of hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of major depression; and whether they have fewer adverse effects than standard antidepressant drugs.. Trials were searched in computerised databases, by checking bibliographies of relevant articles, and by contacting manufacturers and researchers.. Trials were included if they: (1) were randomised and double-blind; (2) included patients with major depression; (3) compared extracts of St. John's wort with placebo or standard antidepressants; (4) included clinical outcomes assessing depressive symptoms.. At least two independent reviewers extracted information from study reports. The main outcome measure for assessing effectiveness was the responder rate ratio (the relative risk of having a response to treatment). The main outcome measure for adverse effects was the number of patients dropping out due to adverse effects.. A total of 29 trials (5489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28 (95% confidence interval (CI), 1.10 to 1.49) and from nine smaller trials was 1.87 (95% CI, 1.22 to 2.87). Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 (95% CI, 0.90 to 1.15; 5 trials) and 1.00 (95% CI, 0.90 to 1.11; 12 trials). Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum. Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (odds ratio (OR) 0.24; 95% CI, 0.13 to 0.46) or SSRIs (OR 0.53, 95% CI, 0.34-0.83).. The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic

There is well documented evidence for the increasing widespread use of complementary and alternative medicine in the treatment of physical and psychiatric symptoms and disorders within Western populations. Here we provide a review of the recent literature on evidence for using such interventions in the treatment of anxiety and depression.. With regard to herbal treatments, kava is effective in reducing anxiety symptoms and St John's wort in treating mild to moderate depression. The association of kava with hepatotoxicity, however, is a significant concern. Promising data continue to emerge for the use of omega-3 fatty acids in managing depression. Evidence for the use of acupuncture in treating anxiety disorders is becoming stronger, although there is currently minimal empirical evidence for the use of aromatherapy or mindfulness-based meditation.. The evidence base for the efficacy of the majority of complementary and alternative interventions used to treat anxiety and depression remains poor. Recent systematic reviews all point to a significant lack of methodologically rigorous studies within the field. This lack of evidence does not diminish the popularity of such interventions within the general Western population.

Topics: Acupuncture Therapy; Anxiety Disorders; Aromatherapy; Cognitive Behavioral Therapy; Combined Modality Therapy; Complementary Therapies; Depressive Disorder; Evidence-Based Medicine; Humans; Hypericum; Kava; Meditation; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic

Many patients look to complementary and alternative medicine for a herbal solution to depression. This literature review summarizes recently published research on the treatment of depression using St. John's wort (Hypericum perforatum).. The compounds in St. John's wort herbal preparations are more effective than placebo and, in several studies, more effective than common antidepressant medications in treating minor depression. However, the efficacy of St. John's wort for treating major depression, cyclothymia, or bipolar disorder is less evident. Although some studies are promising in the treatment of these major disorders, research support is lacking, and it is a controversial aspect of Hypericum therapy.. As with any herbal treatment, risks from adverse reactions and drug interactions exist. Providers have an ethical and legal obligation to stay current in knowledge and to provide useful, accurate information to patients.

Topics: Antidepressive Agents; Bipolar Disorder; Cyclothymic Disorder; Depression; Depressive Disorder; Holistic Nursing; Humans; Hypericum; Nursing Methodology Research; Phytotherapy; Research Design; Treatment Outcome

Natural medications such as St. John's Wort, SAMe, and omega-3 fatty acids eventually may prove to be valuable additions to the psychiatrist's pharmacologic armamentarium, both as monotherapy and as adjunctive therapy for mood disorders. Current research data are compelling, from a standpoint of both efficacy and safety, but before clinicians can recommend these as first-line treatments, more well-designed controlled studies in large patient populations are needed. During the past decade, the National Institutes of Health, the National Institute for Mental Health, and the National Center for Complementary and Alternative Medicine have widened their support for research on the efficacy and safety of alternative treatments, and increasing numbers of academic institutions are undertaking large-scale, multicenter studies on the natural medications reviewed here, as well as others. These studies should help answer some of the yet-unsettled questions about natural medications. Psychiatrists who are considering recommending natural antidepressants to their patients should emphasize that these treatments are relatively unproven and that it remains to be seen whether they would be appropriate or preferable to the conventional psychotropic agents. in the absence of more conclusive data, the best candidates for alternative treatments may be patients for whom a delay in adequate treatment would not be devastating(eg, the mildly symptomatic patient who has a strong interest in natural remedies). Other good candidates may include patients who have been unresponsive to conventional antidepressants or particularly intolerant of side effects; these patients, however, often are the most difficult to treat, and alternative agents seem best suited for the mildly ill. Care should be taken with patients who are taking multiple medications, in view of adverse drug-drug interactions that have emerged with increased use of alternative treatments. Finally, as with all psychotropic agents, natural medications should be used preferably under the supervision of a physician.

Topics: Complementary Therapies; Depressive Disorder; Fatty Acids, Omega-3; Humans; Hypericum; Phytotherapy

St. John's Wort (Hypericum perforatum L.) is commonly accepted as a medicinal plant. The data on the physiological activities of the individual substances that are produced in different organs of H. perforatum are well known at present. The highest attention is focused on the characterization and phytochemical properties of hypericin and hyperforin. These organic compounds are used as antidepressant, anticarcinogenic (photodynamic), antimicrobial and virostatic agents. The review paper surveys the present knowledge of chemical and analytical methods for their identification and quantification, physiological activity, and pharmacological and biomedical applications of hypericin and hyperforin.

Topics: Anthracenes; Antidepressive Agents; Bridged Bicyclo Compounds; Depressive Disorder; Humans; Hypericum; Perylene; Phloroglucinol; Phytotherapy; Plant Extracts; Plants, Medicinal; Terpenes

Derived from the aerial parts of the plant, St. John's wort generally is used for depression, seasonal affective disorder, and anxiety. Products currently are standardized based on hypericin content, although the hyperforin and bioflavonoid contents are also believed responsible for activity. St. John's wort is metabolized primarily by the liver. Some studies comparing St. John's wort to standard antidepressants suggest that it may be as effective as imipramine or selective serotonin reuptake inhibitors (SSRIs) to treat mild to moderate depression. Results from another clinical trial indicate that the effectiveness of St. John's wort is comparable to paroxetine, an SSRI, in the treatment of moderate to severe depression and is well tolerated. But a meta-analysis shows that data are inconsistent. Studies also show possible efficacy in the management of anxiety and premenstrual syndrome, although additional research is necessary. St. John's wort can interact with many medications owing to induction of cytochrome P-450 3A4 and other mechanisms. Significant interactions include decreased efficacy of antiretrovirals, cyclosporine, tacrolimus, antiepileptics, irinotecan, and other chemotherapeutic agents. Serotonin syndrome may occur when St. John's wort is combined with sympathomimetics, antidepressants, or triptans. Frequently reported adverse events include nausea, headache, constipation, dizziness, confusion, fatigue, and dry mouth. St. John's wort should be used under medical supervision.

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Drug Interactions; Humans; Hypericum; Phytotherapy; Plants, Medicinal; Seasonal Affective Disorder; Virus Diseases

Topics: Adult; Antidepressive Agents; Antidepressive Agents, Tricyclic; Cognitive Behavioral Therapy; Combined Modality Therapy; Cyclohexanols; Depressive Disorder; Electroconvulsive Therapy; Humans; Hypericum; Monoamine Oxidase Inhibitors; Morpholines; Phytotherapy; Plant Preparations; Psychotherapy; Reboxetine; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Phytotherapy; Psychotherapy; Risk Factors; Self-Injurious Behavior

Extracts of Hypericum perforatum (St John's wort) are widely used to treat depression. Evidence for its efficacy has been criticised on methodological grounds.. To update evidence from randomised trials regarding the effectiveness of Hypericum extracts.. 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.. 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.. 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.

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Treatment Outcome

We present a systematic review of observational studies of hypericum extracts in the treatment of depressive disorders. We included non-randomized studies with at least 100 patients suffering from depressive disorders treated with hypericum mono-preparations for at least 4 weeks, which reported clinical outcomes. Potentially relevant studies were identified through searches in electronic databases (Medline, PubMed), contacts with manufacturers, and handsearching of proceedings of phytomedicine congresses. Information on patients, interventions, methods an results were extracted by two reviewers. Sixteen studies including a total of 34,804 (range 101-11,296) patients met the inclusion criteria. Most studies investigated short-term effects (4-6 weeks) in patients with mild to moderate depression. Response rates (according to physician assessment) varied between 65% and 100%, the proportion of patients dropping out due to side effects varied between 0.0% and 2.8%. Two studies investigated long-term effects (52 weeks). Reponse rates were 60% and 69%, respectively, and the proportions of patients dropping out due to side effects were 3.4% and 5.7%, respectively. Serious side effects or interactions were not reported in any study. The quality of reporting was insufficient in the majority of publications. The available studies show that hypericum extract are well tolerated and seem to be effective in routine treatment of mild to moderate depressive disorders.

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Psychiatric Status Rating Scales; Treatment Outcome

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.. 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.. 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.. 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.. 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.. 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).. 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.

Topics: Adult; Depressive Disorder; Humans; Hypericum; Phytotherapy; Randomized Controlled Trials as Topic

Nurses need to become more aware of serotonin syndrome to avoid its development and to ensure a therapeutic response when early symptoms emerge. While polypharmacy tends to put individuals at greatest risk for the syndrome, use of a single serotonergic agent may also provoke an adverse response. Because the onset and progression of serotonin syndrome are rapid, prompt action may be needed to avoid potentially life-threatening consequences.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Drug Therapy, Combination; Female; Fluoxetine; Humans; Hypericum; Incidence; Medical History Taking; Migraine Disorders; Nurse's Role; Nursing Assessment; Phototherapy; Primary Prevention; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Serotonin Syndrome; Sumatriptan

St. John's Wort (SJW, Hypericum perforatum) is effective in mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, numerous reports indicate the possibility of important interactions with prescribed drugs. SJW has been shown to lower the plasma concentration (and/or the pharmacological effect) of a number of drugs including alprazolam, amitriptyline, cyclosporine, digoxin, fexofenadine, indinavir, irinotecan, methadone, nevirapine, simvastatin, tacrolimus, theophylline, warfarin, phenprocoumon and oral contraceptives. Induction of P-glycoprotein and/or cytochrome P450 (CYP) enzymes (particularly CYP 3A4) by SJW could explain such pharmacokinetic interactions. When combined with serotonin reuptake inhibitor, antidepressants (e.g. sertaline, paroxetine, nefazodone) or buspirone, SJW can cause serotonergic syndrome. SJW represents a herbal medicine with a high potential for drug interactions. Some of such interactions may have serious clinical consequences.

Topics: Adult; Area Under Curve; Depressive Disorder; Female; Herb-Drug Interactions; Humans; Hypericum; Immunosuppressive Agents; Male; Middle Aged; Organ Transplantation; Phytotherapy; Plant Extracts; Selective Serotonin Reuptake Inhibitors

St. John's wort (Hypericum perforatum) has been identified as an effective treatment for depression in controlled studies and subsequent meta-analyses. However, 3 recently published large studies failed to demonstrate robust efficacy. Updated meta-analysis and assessment of publication bias may help determine the true effect of St. John's wort.. Meta-analysis to reevaluate the effectiveness of St. John's wort as an antidepressant, funnel plot analysis, and meta-regression to assess the impact of publication bias, small-study effects, and variation in trial characteristics were performed. We conducted 2 analyses: a reproduction of a recent meta-analysis including 15 studies (Meta-15) and a meta-analysis extended by the 3 studies published since then (Meta-18). The studies in Meta-15 were identified through MEDLINE and EMBASE searches conducted in June 2000. The search terms used were St. John's wort, hypericum, hypericin, depression, and antidepressant, and no language restrictions were applied. For both meta-analyses, we compared funnel plots, Begg's rank correlation, Egger's regression, trim and fill method, and meta-regression.. In both analyses, effect sizes in recent studies were smaller than those reported in earlier studies; the addition of more recent studies into the analyses resulted in reduced effect size. In Meta-15, St. John's wort was significantly more effective than placebo with a risk ratio (RR) of 1.97 (CI = 1.54 to 2.53). In Meta-18, the RR was reduced to 1.73 (CI = 1.40 to 2.14). On funnel plot analysis, the Meta-18 plot proved to be much more skewed than the Meta-15 plot. Meta-regression showed that increase in effect size was associated with smaller sample size only. The impact of baseline severity of depression could not be evaluated as the studies used different versions of the Hamilton Rating Scale for Depression.. St. John's wort may be less effective in the treatment of depression than previously assumed and may finally be shown to be ineffective if future trials confirm this trend.

Topics: Depressive Disorder; Humans; Hypericum; Phytotherapy; Placebos; Publication Bias; Regression Analysis; Severity of Illness Index; Treatment Outcome

After anxiety, depression is one of the most common psychiatric diseases, showing a lifetime prevalence of 4.4 - 18 %. St. John's Wort is a herbal antidepressant combining a long tradition of use with well-proven medical research. We conducted a meta-analysis to review St. John's Wort's place in the treatment of depression. A comprehensive literature search was conducted for studies comparing effectiveness and tolerability of St. John's Wort with either placebo or synthetic antidepressant. Thirty studies met the inclusion as well as the quality criteria and were included in the meta-analysis. Four studies consisted of all three arms and were thus included in both analyses. Our results demonstrated a significant advantage for St. John's Wort compared to placebo (n = 2129, RR = 0.66, 95 % CI 0.57 - 0.78, p < 0.00001, NNT = 4.2 95 % CI 3.0 - 6.6, mean response: 53.3 vs. 32.7 %). Compared to synthetic antidepressants St. John's Wort demonstrated similar effectiveness (n = 2231, RR = 0.96, 95 % CI 0.85 - 1.08, p = 0.5, mean response: 53.2 % vs. 51.3 %). In the sub-group of mild to moderate depression, corresponding with the indication for St. John's Wort assigned by the German health authority, the herbal antidepressant showed better results against the synthetic antidepressants (n = 1166, RR = 0.85, 95 % CI 0.75 - 0.97, p = 0.01, NNT = 14.3, 95 % CI 8.3 - 100, mean response 59.5 vs. 52.9 %). This result viewed together with St. John's Wort's favourable side-effects profile, leading to a lower rate of drop-outs, suggests treatment with St. John's Wort should be attempted for milder forms of depression. Funnel plot analysis suggested publication bias could exist for the comparison with placebo. To put this in a perspective the fail-safe-N-test calculated that 423 studies with no effect would be needed to negate the presented result for placebo studies.

Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Phytotherapy; Research Design

Depression is the most prevalent psychiatric disorder in transplant recipients and may lead to noncompliance and negative outcomes without psychosocial and pharmacologic interventions. The pharmacologic treatment of depression in this patient population is complicated by complex immunosuppressant drug regimens and multiple potential drug interactions that can adversely affect the newly transplanted organs. This review provides a brief overview of the currently available antidepressant medications and highlights the clinically important features each class of agents in transplant recipients. Newer agents selective serotonin reuptake inhibitors, venlafaxine, bupropion, nefazodone, and mirtazapine are discussed as well as tricyclic antidepressants and monoamine oxidase inhibitors. A brief discussion of St. John's wort and its impact on posttransplant drug therapy is also included.

Topics: Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Antagonists; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depressive Disorder; Drug Monitoring; Humans; Hypericum; Monoamine Oxidase Inhibitors; Neurotransmitter Uptake Inhibitors; Organ Transplantation; Patient Selection; Phytotherapy; Safety; Serotonin 5-HT2 Receptor Antagonists; Treatment Outcome; Treatment Refusal

The purpose of this paper is to review preclinical and clinical evidence relating to drug interactions with preparations of the medicinal herb St John's wort (Hypericum perforatum). A systematic literature search was carried out in three electronic databases up to June 2004. Information about case reports classified as St John's wort drug interactions was retrieved from the WHO Collaborating Centre for International Drug Monitoring and from the UK Medicines and Healthcare products Regulatory Agency in June 2003. 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.

Topics: Animals; Area Under Curve; Cytochrome P-450 Enzyme System; Depressive Disorder; Drug Interactions; Female; Humans; Hypericum; Male; Pharmacokinetics; Phytotherapy; Plant Preparations

This review evaluates the research published between 1966 and 2004 on several integrative treatments for depression, including omega-3 fatty acids, Hypericum perforatum (St. John's Wort), S-adenosyl-methionine, folate, 5-Hydroxytryptophan, acupuncture, exercise, and light therapy, with a particular emphasis on issues pertinent to women. Data from double-blind, placebo-controlled trials support each of these as treatment interventions for depression. We discuss both the strength of the evidence for each treatment and methodological issues related to interpretation of efficacy. Available data pertaining to considerations in women, including use during pregnancy and breastfeeding and interactions with hormonal therapies are discussed. The reviewed treatments deserve further research. Their appropriate place in the armamentarium of depression treatments for women must be defined. An evidence-based integrative medicine approach brings together treatment options with proven efficacy and the public's desire for complementary and alternative medicine treatments.

Topics: 5-Hydroxytryptophan; Acupuncture Therapy; Complementary Therapies; Depressive Disorder; Exercise Therapy; Fatty Acids, Omega-3; Female; Folic Acid; Humans; Hypericum; Life Style; Phototherapy; Phytotherapy; Pregnancy; Randomized Controlled Trials as Topic; Research Design; S-Adenosylmethionine; Stress, Psychological; United States; Women's Health

Topics: Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Combined Modality Therapy; Depressive Disorder; Electroshock; Humans; Hypericum; Monoamine Oxidase Inhibitors; Phytotherapy; Psychotherapy; Selective Serotonin Reuptake Inhibitors

Preparations from St. John's wort extracts are used in the treatment of depression in many countries and represent an accepted alternative to synthetic antidepressants or behavioural therapy. St. John's wort extracts are therefore used in a therapeutic area which extends well beyond the traditional field of herbal medicine. The current status of preclinical and clinical research is summarised. St. John's wort extract has a clear inhibitory effect on the neuronal uptake not only of serotonin, noradrenaline, and dopamine but also of gamma-aminobutyric acid (GABA) and L-glutamate. No other antidepressant shows an approximately equally broad inhibitory profile. In good agreement with the effects in various biochemical models of antidepressant action, many effects in a number of behavioural pharmacology models of antidepressant efficacy could also be demonstrated for St. John's wort extract. Similar doses of John's wort also cause changes in the above-mentioned neurotransmitter systems in the brain. Out of all individual substances of St. John's wort only hyperforin and its structural analogue adhyperforin inhibit the re-uptake of the investigated neurotransmitters. However, hyperforin does not act as a competitive inhibitor at the transmitter binding sites of the transporter proteins but it affects the sodium gradient which then leads to an inhibition of uptake. The broad spectrum of action which characterises St. John's wort extracts has only been described for the pure substance hyperforin. Over the past year a number of good clinical studies have been carried out which confirm the efficacy and tolerability of St. John's wort extracts in mild depressive disorders, even if the therapeutic efficacy has recently been questioned by an American study. All studies have confirmed the good tolerability of St. John's wort extract and the very low frequency of adverse events. However, some drug interactions have been found to occur with St. John's wort extract, a number of which are of clinical relevance. In summary, pharmacological activity and therapeutic efficacy of St. John's wort extract as an antidepressant are supported by a large number of scientific publications. Within the wide range of components in St. John's wort extract, hyperforin plays an important, if not an outstanding role.

Topics: Animals; Antidepressive Agents; Behavior; Bridged Bicyclo Compounds; Depressive Disorder; Humans; Hypericum; Norepinephrine; Phloroglucinol; Phytotherapy; Receptors, Serotonin; Serotonin; Synaptic Transmission; Terpenes

Topics: Adolescent; Antidepressive Agents, Tricyclic; Child; Cognitive Behavioral Therapy; Cyclohexanols; Depressive Disorder; Electroconvulsive Therapy; Humans; Hypericum; Lithium; Monoamine Oxidase Inhibitors; Phytotherapy; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride

Topics: Depressive Disorder; History, 16th Century; History, Ancient; Humans; Hypericum; Plant Extracts

Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain Chemistry; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Rats

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Psychiatric Status Rating Scales

Topics: Antidepressive Agents; Depressive Disorder; Drug Interactions; Humans; Hypericum; Phytotherapy

Topics: Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Combined Modality Therapy; Depressive Disorder; Electroconvulsive Therapy; Humans; Hypericum; Patient Care Team; Phytotherapy; Psychotherapy

Clinical studies, conducted chiefly in hospital settings, have demonstrated that antidepressant drug therapy is effective treatment for major depressive disorder of at least moderate severity, and that cognitive therapy is an effective alternative to antidepressants in mild to moderate major depression. However, few clinical trials have taken place in general practice, where the great majority of patients with depression are managed. Most such patients in this setting do not meet diagnostic criteria for major depression, and are often described more loosely as having 'mild depression'. Many are given an antidepressant, often as the first step in treatment. Here, we consider whether this is the optimal approach for adults with mild depression in general practice.

Topics: Depressive Disorder; Family Practice; Humans; Hypericum; Phytotherapy; Plant Extracts; Psychotherapy; Self Care

Depression is underdiagnosed and undertreated though its high prevalence and life-threatening character. Once identified, depression can be treated successfully with antidepressants, cognitive behavior therapy/interpersonal psychotherapy or a combination of both. Regarding selection of a particular antidepressant, newer, selective drugs are preferred due to better tolerability and low toxicity.

Topics: Aged; Antidepressive Agents; Depressive Disorder; Emergencies; Family Practice; Female; Hospitalization; Humans; Hypericum; Male; Phytotherapy; Plant Preparations; Psychotherapy; Referral and Consultation; Time Factors

This article is a critical review of the efficacy of selected alternative treatments for unipolar depression including exercise, stress management techniques, acupuncture, St. John's wort, bright light, and sleep deprivation. Issues related to women across the life span, including pregnancy and lactation, are highlighted.. Evidence of efficacy is based on randomized controlled trials. A distinction is made between studies that address depressive symptoms and studies that address depressive disorders. The review emphasizes issues related to effectiveness, such as treatment availability, acceptability, safety, and cost and issues relevant to women.. Exercise, stress reduction methods, bright light exposure, and sleep deprivation hold greater promise as adjuncts to conventional treatment than as monotherapies for major depression. The evidence to date is not sufficiently compelling to suggest the use of St. John's wort in favor of or as an alternative to existing U.S. Food and Drug Administration-regulated compounds. Initial evidence suggests that acupuncture might be an effective alternative monotherapy for major depression, single episode.. This review indicates that some unconventional treatments hold promise as alternative or complementary treatments for unipolar depression in women and have the potential to contribute to its long-term management. Additional research is needed before further recommendations can be made, and there is an urgent need to carefully document and report the frequency of minor and major side effects.

Topics: Acupuncture; Complementary Therapies; Costs and Cost Analysis; Depressive Disorder; Exercise Therapy; Female; Herbal Medicine; Humans; Hypericum; Male; Phototherapy; Phytotherapy; Randomized Controlled Trials as Topic; Relaxation Therapy; Sex Factors; Sleep Deprivation; Stress, Psychological; Treatment Outcome

Atypical depression, somatoform disorder, neurasthenia and fibromyalgia seem to form a spectrum of disorders, who share a common biological basis, i.e. a reduced activity of the hypothalamus-pituitary-adrenocortical (HPA)-system. This is similar to the situation in Cushing's disease, where the central part of the hypothalamus-pituitary-adrenocortical-system is decreased by an increased feedback via increased intracerebral cortisol concentration. Cushing's disease is accompanied by features of atypical depression and of somatisation. Treatment with hypericum seems to disinhibit the hypothalamus-pituitary-adrenocortical-system in healthy subjects and patients with a depression. Furthermore it decreases intracerebral corticosteroids, possibly by increasing the expression of p-glycoprotein at the blood brain barrier. Therefore hypericum might be especially effective in patients with a symptom cluster of atypical depressive features and somatisation. Clinical studies with patients with depression with atypical features like the seasonal affective disorder (SAD) and with patients with a depressive syndrome accompanied by somatic complaints or fatigue support this view.

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Fibromyalgia; Humans; Hypericum; Hypothalamo-Hypophyseal System; Neural Inhibition; Neurasthenia; Phytotherapy; Pituitary-Adrenal System; Plant Extracts; Somatoform Disorders; Treatment Outcome

Topics: Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Plant Extracts; Treatment Outcome

Topics: Depressive Disorder; Humans; Hypericum; Neoplasms; Phytotherapy; Plant Extracts

Saint John's wort (Hypericum perforatum L.) is a herbal remedy that is effective in the treatment of mild to moderate depression. In traditional folk medicine, oily extracts of St. John's wort are used for topical treatment of wounds, burns and myalgia. The lipophilic phloroglucin-derivative hyperforin has antibacterial and antiinflammatory effects. These effects could be of relevance in topical treatment of infected wounds and other dermatoses, but no studies have been conducted so far. The naphtodianthrone hypericin is a photodtodynamic active substance that kills tumor cells via the induction of apoptosis. Hypericin also displays antiviral activity in vitro. In vivo, intravenous or oral treatment with hypericin of HIV-infected subjects did not result in a reduction of the virus load. Most of the patients treated with hypericin experienced phototoxicity. Similar phototoxic symptoms ("hypericism") have been observed in grazing animals ingesting large amounts of St. John's wort. In contrast, antidepressant medication with St. John's wort usually does not produce phototoxic symptoms. Recent pharmacokinetic studies suggest that the phototoxic threshold level of hypericin is not reached with dosages used for the oral treatment of depression. However, very recent reports demonstrated interactions of St. John's wort with other drugs such as digoxin, indinavir and cyclosporin. Blood levels of these drugs were dramatically decreased by St. John's wort. This should be considered in the treatment of skin conditions with antiviral drugs or cyclosporin.

Topics: Depressive Disorder; Humans; Hypericum; Photosensitivity Disorders; Phytotherapy; Plant Extracts; Skin Diseases

The chemical composition of St. John's wort has been well-studied. Documented pharmacological activities, including antidepressant, antiviral, and antibacterial effects, provide supporting evidence for several of the traditional uses stated for St John's wort. Many pharmacological activities appear to be attributable to hypericin and to the flavonoid constituents; hypericin is also reported to be responsible for the photosensitive reactions that have been documented for St. John's wort. With regard to the antidepressant effects of St John's wort, hyperforin, rather than hypericin as originally thought, has emerged as one of the major constituents responsible for antidepressant activity. Further research is required to determine which other constituents contribute to the antidepressant effect. Evidence from randomised controlled trials has confirmed the efficacy of St John's wort extracts over placebo in the treatment of mild-to-moderately severe depression. Other randomised controlled studies have provided some evidence that St John's wort extracts are as effective as some standard antidepressants in mild-to-moderate depression. There is still a need for further trials to assess the efficacy of St John's wort extracts, compared with that of standard antidepressants, particularly newer antidepressant agents, such as the selective serotonin reuptake inhibitors (recent comparative studies with fluoxetine and sertraline have been conducted). Also, there is a need for further studies in well-defined groups of patients, in different types of depression, and conducted over longer periods in order to determine long-term safety. St John's wort does appear to have a more favourable short-term safety profile than do standard antidepressants, a factor that is likely to be important in patients continuing to take medication. Concerns have been raised over interactions between St John's wort and certain prescribed medicines (including warfarin, ciclosporin, theophylline, digoxin, HIV protease inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, triptans, oral contraceptives); advice is that patients taking these medicines should stop taking St John's wort, generally after seeking professional advice as dose adjustment of conventional treatment may be necessary.

Topics: Adult; Bacterial Infections; Depressive Disorder; Drug Interactions; Female; Humans; Hypericum; Male; Phytotherapy; Plants, Medicinal; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Seasonal Affective Disorder; Virus Diseases

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.

Topics: Anthracenes; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Perylene; Phytotherapy; Treatment Outcome

Hypericum Perforatum Extract is an extract of the capsules, flowers, leaves, and stem heads of Hypericum perforatum, commonly called St. John's Wort. Hypericum Perforatum Oil is the fixed oil from H. perforatum. Techniques for preparing Hypericum Perforatum Extract include crushing in stabilized olive oil, gentle maceration over a period of weeks, followed by dehydration and filtration. Propylene Glycol and Butylene Glycol extractions were also reported. The following components have variously been reported to be found in H. perforatum: hypericin, naphtodianthrones, flavonoids, terpene and sesquiterpene oils, phenylpropanes, biflavones, tannins, xanthones, phloroglucinols, and essential oils. Hypericum Perforatum Extract is used in over 50 cosmetic formulations and Hypericum Perforatum Oil in just over 10, both across a wide range of product types. Acute toxicity studies using rats, guinea pigs, and mice indicate that the extract is relatively nontoxic. Animals fed H. perforatum flowers for 2 weeks showed significant signs of toxicity, including erythema, edema of the portion of the body exposed to light, alopecia, and changes in blood chemistry. In a chronic study, rats fed H. perforatum gained less weight than control animals. Mixtures containing the extract and the oil were not irritants or sensitizers in animals. Because of the presence of hypericin, H. perforatum is a primary photosensitizer. In clinical tests, a single oral administration of Hypericum extract resulted in hypericin appearing in the blood. With long-term dosing, a steady-state level in blood was reached after 14 days. The polyphenol fraction of H. perforatum had immunostimulating activity, whereas the lipophilic portion had immunosuppressing properties. Mixtures of the extract and the oil produced minimal or no ocular irritation in rabbit eyes. Mutagenic activity in an Ames test was attributed to flavonols in one study and to quercitin in another, but other genotoxicity assays were negative. No carcinogenicity or reproductive and developmental toxicity data were available. A mixture of the extract and the oil was not irritating in clinical studies. Adverse reactions to Hypericum extract in the clinical treatment of depression include skin reddening and itching, dizziness, constipation, fatigue, anxiety, and tiredness. Absent any basis for concluding that data on one member of a botanical ingredient group can be extrapolated to another in a group, or to the same ingredient extracted di

Topics: Administration, Oral; Animals; Anthracenes; Chemistry, Pharmaceutical; Cosmetics; Depressive Disorder; Dizziness; Fatigue; Guinea Pigs; Humans; Hypericum; Immune System; Mice; Mutagenicity Tests; Perylene; Photosensitivity Disorders; Plant Preparations; Rats; Safety; Skin Diseases; Toxicity Tests

Many of the diagnostic and therapeutic procedures in psychiatry and psychotherapy are based on opinion rather than evidence. The concept of evidence-based medicine aims to bridge the gap between clinical research and clinical decision-making by integrating the best available external evidence with personal expertise. In this article, we demonstrate several examples of the non-evidence-based medicine paradigm. Then we show the usefulness and practicability of the new evidence-based medicine paradigm by using a clinical example. Finally, we discuss the consequences, chances, and limitations of this new model. We also examine the role of the individual clinician's viewpoint as well as the need of institutional re-engineering and the possible restructuring of the entire health care system towards evidence-based methods.

Topics: Antidepressive Agents, Tricyclic; Delivery of Health Care; Depressive Disorder; Evidence-Based Medicine; Humans; Hypericum; Phytotherapy; Plants, Medicinal; Psychiatry; Psychotherapy; Randomized Controlled Trials as Topic; Total Quality Management

Depressive disorders are persistent, recurring illnesses that cause great suffering for patients and their families.. To evaluate the benefits and adverse effects of newer pharmacotherapies and herbal treatments for depressive disorders in adults and adolescents.. English-language and non-English-language literature from 1980 to January 1998 was identified from a specialized registry of controlled trials, meta-analyses, and experts.. Randomized trials evaluating newer antidepressants (such as serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and St. John's wort) that reported clinical outcomes were selected.. Two persons independently abstracted data that were then synthesized descriptively; some data were pooled by using a random-effects model.. Of 315 eligible trials, most evaluated antidepressants in adults with major depression, were conducted among outpatients, and examined acute-phase treatment. Newer antidepressants were more effective than placebo for major depression (relative benefit, 1.6 [95% CI, 1.5 to 1.7]) and dysthymia (relative benefit, 1.7 [CI, 1.3 to 2.3]). They were effective among older adults and primary care patients. Efficacy did not differ among newer agents or between newer and older agents. Hypericum (St. John's wort) was more effective than placebo for mild to moderate depression (risk ratio, 1.9 [CI, 1.2 to 2.8]), but publication bias may have inflated the estimate of benefit. Newer and older antidepressants did not differ for overall discontinuation rates, but side effect profiles varied significantly. Data were insufficient for determining the efficacy of newer antidepressants for subsyndromal depression, depression with coexisting medical or psychiatric illness, or depression in adolescents.. Newer antidepressants are clearly effective in treating depressive disorders in diverse settings. Because of similar efficacy, both newer and older antidepressants should be considered when making treatment decisions. Better information is urgently needed on the efficacy of newer antidepressants in patients with nonmajor depression and in special populations, including adolescents.

Topics: Age Factors; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depressive Disorder; Humans; Hypericum; Lymphatic Diseases; Monoamine Oxidase Inhibitors; Patient Dropouts; Phytotherapy; Plants, Medicinal; Practice Guidelines as Topic; Selective Serotonin Reuptake Inhibitors; Thymus Gland

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.. 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.. 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.. 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.. 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.. 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).. 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.

Topics: Adult; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal

St John's wort (Hypericum perforatum) has a 2000-year history of use as a medicinal herb. Its modern application as a plant extract for treating depression has undergone scientific investigation over the last decade, and its effectiveness has been shown in studies comparing it with placebo and reference antidepressants. Our own work supports the contention that LI 160, the best-documented St John's wort medication, is effective at a high dosage even in patients with severe depression. Since the new Berlin Aging Study revealed significant treatment deficiencies among elderly depressive patients, St John's wort extracts may be a useful alternative to benzodiazepines to avoid nontreatment of early depression. Because St John's wort preparations have better tolerability than tricyclic antidepressants, elderly people in particular, can benefit from their use.

Topics: Aged; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal

Although in Germany St. John's wort (Hypericum perforatum) is the most widely prescribed antidepressant, in the Netherlands little is known about it. Nevertheless patients ask for it more often or take it as self-medication. There has been much research into the antidepressant efficacy of hypericum extracts, but the methodological quality has been moderate. In recent years studies with a much better design were published in European journals. Hypericum extract in a dosage of 900 mg/day is effective in mild to moderately severe depressed outpatients. Maintenance therapy has not been studied sufficiently yet. The side effect profile is on a placebo level. Recently interactions with other medications were described (decrease of plasma level/clinical efficacy of protease inhibitors, warfarin, theophyllin, cyclosporin, third generation oral contraconceptives, digoxin and phenprocoumon). A patient's request to be treated with hypericum extract can be considered, e.g. if the patient experiences troublesome side effects on other drugs. In case hypericum is the initial antidepressant and the effect falls short of the expectations, treatment with a synthetic standard antidepressant should be applied.

Topics: Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Drug Interactions; Formularies as Topic; Humans; Hypericum; Netherlands; Phytotherapy; Plants, Medicinal; Randomized Controlled Trials as Topic

Several medications have recently been introduced for the treatment of depression. We reviewed the literature to summarize their efficacy in the treatment of depression in adult patients in primary care settings.. We searched the literature published from 1980 to January 1998 using the Cochrane Collaboration Depression Anxiety and Neurosis Group's specialized registry of 8,451 clinical trials, references from trials and 46 pertinent meta-analyses, and consultation with experts. We included randomized controlled trials of at least 6 weeks' duration that measured clinical outcomes and compared one of 32 newer medications with another newer antidepressant, an older antidepressant, a placebo, or a psychosocial intervention for the treatment of depressed patients in primary care settings. The primary outcome was response rate, defined as the proportion of patients experiencing a 50% or greater improvement in depressive symptoms.. There were 28 randomized controlled trials involving 5,940 adult primary care patients with major depression, depression requiring treatment, dysthymia, or mixed anxiety depression. Newer agents, including selective serotonin re-uptake inhibitors, serotonin norepinephrine inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists, were usually compared with tricyclic agents. Average response rates were 63% for newer agents, 35% for placebo, and 60% for tricyclic agents. Newer agents were significantly more effective than placebo [risk ratio = 1.6; 95% confidence interval (CI), 1.2 to 2.1), but similar to tricyclic agents (risk ratio = 1.0; 95% CI, 0.9 to 1.1). Response rates were similar in the different types of depressive disorders, except that two small trials in frail older patients showed no significant effects of newer agents compared with placebo. Dropout rates as a result of adverse effects were 8% with newer agents and 13% with tricyclic agents (P <0.05).. In primary care settings, newer antidepressants are more effective than placebo and have similar efficacy compared with tricyclic agents in the acute treatment of depression. Dropout rates as a result of adverse effects are lower with newer compared with tricyclic agents. Future studies should compare the effectiveness of different therapies among primary care patients with less severe depression and greater medical and psychiatric comorbidity.

Topics: Antidepressive Agents, Second-Generation; Depression; Depressive Disorder; Dopamine Antagonists; Dopamine Uptake Inhibitors; Evidence-Based Medicine; GABA Agents; Humans; Hypericum; Monoamine Oxidase Inhibitors; Phytotherapy; Plants, Medicinal; Primary Health Care; Publication Bias; Randomized Controlled Trials as Topic; Research Design; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; United States

Many unregulated over-the-counter agents for the treatment of depression are now available to patients and consumers. The potential for adverse neuropsychiatric effects with these agents has not been systematically studied in most cases.. The author performed a MEDLINE search on a variety of herbal and nonherbal over-the-counter agents said to be useful in the treatment of depression. The Physicians' Desk Reference for Herbal Medicines was also consulted.. Although many of the herbal agents said to have benefits in depression appear to be safe, serious neuropsychiatric side effects and interactions have been reported for several over-the-counter "antidepressants." There is reason to suspect underreporting of those adverse events. Moreover, there is very little evidence from systematic studies regarding the potential for drug-drug or herb-drug interactions with these over-the-counter agents. Vitamins and amino acids touted for the treatment of depression are also not without risk.. Although some over-the-counter remedies for depression are probably safe and effective for as-yet unidentified subgroups of depressed individuals, more research is required before these agents can be recommended for routine use. Stricter U.S. Food and Drug Administration oversight of these agents is indicated.

Topics: Adverse Drug Reaction Reporting Systems; Antidepressive Agents; Dehydroepiandrosterone; Depressive Disorder; Drug Information Services; Drug Interactions; Humans; Hypericum; Inositol; Mental Disorders; Nonprescription Drugs; Phytotherapy; Plants, Medicinal; Psychoses, Substance-Induced; S-Adenosylmethionine

Over the last few years St-John's wort preparations have been used in large quantities in Germany for treating mild to moderate depression. In the meantime the antidepressive action of these extracts has been proved in numerous placebo-controlled studies. Furthermore, a considerably lower adverse effect rate compared with classic antidepressants has been established. Analogously to other antidepressants, subchronic St-John's wort treatment of rats showed significant down-regulation of beta receptor density and a significant increase in 5HT2 receptors. The extract also exhibited antidepressant activity in animal pharmacological models of depression. Interest is now focused on identifying the underlying pharmacological mechanisms of action of this phytotherapeutic agent. Like other working parties, we were only able to identify a weak inhibitory effect of the extract and the pure substance hypericin on the monoamine oxidases A and B. Similarly to synthetic antidepressants, St-John's wort exerts marked inhibitory effects on synaptosomal uptake of serotonin and noradrenaline. However, dopamine and uptake and neuronal uptake of GABA and L-glutamate are also inhibited. These effects may mainly be attributed to the substance hyperforin contained in the extract. An additional, as yet unknown, pharmacological mechanism of action of St-John's wort extracts is beginning to emerge. Although hyperforin shows similar properties to classical antidepressants, there are indications of a novel mechanism of action. Our laboratory is currently investigating the means by which St-John's wort extract, or its constituent hyperforin, develops its antidepressant action.

Topics: Animals; Brain; Depressive Disorder; Humans; Hypericum; Plant Extracts; Plants, Medicinal; Receptors, Neurotransmitter

Observational studies with preparations of St. John's wort have recorded an incidence of adverse events (AE) among those treated of between 1 and 3%. This is some ten times less than with synthetic antidepressants. The most common adverse events (1 per 300,000 treated cases) among the spontaneous reports in the official register concern reactions of the skin exposed to light. Investigations in volunteers have shown that the threshold dose for an increased risk of photosensitisation is about 2-4 g/day of a usual commercial extract (equivalent to approximately 5-10 mg of the hypericin that causes the phenomenon). In view of the newly observed side effects and interactions, the following additional restrictions on use appear justified: as with all preparations in this group of indications, hypericum preparations must not be taken at the same time as other antidepressants. If co-medication with coumarin-type anticoagulants is unavoidable, it must only be undertaken provided clotting parameters are closely monitored by the physician. Co-medication with cyclosporin and indinavir, and for the time being, other protease inhibitors used in anti-HIV treatment, is absolutely contraindicated. Without exception, all preparations of St. John's wort must only be available through pharmacies.

Topics: Antidepressive Agents; Depressive Disorder; Drug Interactions; Herb-Drug Interactions; Humans; Hypericum; Plant Extracts; Plants, Medicinal; Risk Factors

70-90% of depressive patients are treated by their own family doctors. Recognising and treating depression is an important daily problem for family doctors. The severity of the disorder decides whether non-pharmacological therapy or pharmacotherapy is preferable. The choice and dosage of an antidepressant is dictated by the severity and the symptomatology of the disorder as well as the expected adverse effects. Not least on account of their low rate of adverse effects, phytotherapeutic agents are enjoying growing popularity among patients and thus assure high compliance. The use of herbal preparations is useful, in particular for mild to moderate depression in young patients or patients with a reserved attitude toward "chemical drugs". Of all phytopharmaceuticals St.-John's wort has been most widely scientifically documented for the treatment of depression.

Topics: Adult; Depressive Disorder; Family Practice; Humans; Hypericum; Patient Care Team; Phytotherapy; Plant Extracts; Plants, Medicinal; Treatment Outcome

In 1998 a standardized hypericum extract has been approved in Austria and Germany for treatment of mild and moderate depression. The efficacy has been already recognized since 1984 from the German Health Authorities based on traditional knowledge. However, this has been substantiated in the subsequent years in controlled clinical trials. Twenty of these studies including a total of 1787 patients have been filed, among them ten older studies in which hypericum was extracted with ethanol compared to newer studies in which the extract was methanol (LI 160). In the past ten years several controlled clinical trials have been conducted compared with placebo as well as synthetic antidepressants. These studies have shown that the effective dosage is within a range of 600-900 mg extract. The side effects are substantially fewer than with synthetic antidepressants and range within 3%. The most important risk is photosensitization, which is however without clinical relevance in the recommended dosages. Recent pharmacological studies revealed that hypericum extracts have a similar mechanism of action like the selective serotonin reuptake inhibitors (SSRI), however, very likely to a smaller extent.

Topics: Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plant Extracts; Plants, Medicinal; Treatment Outcome

In 1998 a special standardized high-dose hypericum extract has been approved in Austria and Germany for treatment of mild and moderate depression. The efficacy has been already recognized since 1984 from the German Health Authorities based on traditional knowledge. However, this has been substantiated in the subsequent years in controlled clinical trials. 20 of these studies including a total of 1,787 patients have been filed, among them 10 older studies in which hypericum was extracted with ethanol compared to newer studies in which the extract was methanol (LI 160). In the past 10 years several controlled clinical trials have been conducted compared with placebo as well as synthetic antidepressants. These studies have shown that the effective dosage is within a range of 600 to 900 mg extract. The side effects are substantially fewer than with synthetic antidepressants and range within 3%. The most important risk is photosensitization, which is however without clinical relevance in the recommended dosages. Recent pharmacological studies revealed that hypericum extracts have a similar mechanism of action like the selective serotonin reuptake inhibitors (SSRI), however, very likely to a smaller extent.

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Humans; Hypericum; Plant Extracts; Plants, Medicinal; Treatment Outcome

Topics: Depressive Disorder; Family Practice; Humans; Hypericum; Male; Materia Medica; Middle Aged; Nonprescription Drugs; Phytotherapy; Plants, Medicinal

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Nonprescription Drugs; Perylene; Plants, Medicinal; Quercetin; Xanthenes

St. John's Wort (Hypericum perforatum), a perennial flowering plant, has been used medicinally for thousands of years, and has most recently been identified as an effective treatment for mild to moderate depression. Clinical studies on the use of this plant for depression have utilized liquid tinctures and standardized solid extracts (0.3% hypericin--300 mg three times a day). Severe depression may also respond to this botanical, although it appears a larger dose is needed (600 mg solid extract three times a day). Hypericum has been favorably compared to numerous antidepressant drugs, the studies having revealed equivalent results and a much more favorable incidence of side effects. Studies have also demonstrated its efficacy in treating seasonal affective disorder. In vitro investigations of Hypericum show antiviral activity, although there is evidence these promising results might not occur in vivo. Traditional actions and uses include enhancement of wound healing, as well as anti-inflammatory and analgesic activity.

Topics: Depression; Depressive Disorder; Humans; Hypericum; Perylene; Plant Extracts; Plants, Medicinal; Quercetin; Xanthenes

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.

Topics: Antidepressive Agents; Controlled Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Perylene; Plant Extracts; Plants, Medicinal; Quercetin; Xanthenes

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.. 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.

Topics: Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Drug Combinations; Humans; Hypericum; Perylene; Plant Extracts; Plants, Medicinal; Quercetin; Randomized Controlled Trials as Topic; Treatment Outcome; Xanthenes

The Italian Medieval doctor Thaddeus Florentinus (AD 1210-1295) claimed that herbs could cure or relieve various symptoms such as obstipation, melancholia and nervousness. Additionally, certain herbs were proposed to be able to predict the weather and induce the vision of elves. Therefore, the aim of this study was to investigate whether herbs could have medical properties as claimed.. A randomized controlled trial with three arms was conducted: 1) Gin with St. John's wort, 2) Gin with angelica and 3) Gin with sweet woodruff. Participants were 21 anesthesia registrars. The primary outcome was visual induction of elves (yes/no) whereas secondary outcomes included melancholia (VAS 0-100), nervousness (VAS 0-100), weather prediction capabilities (yes/no) obstipation (Bristol Stool Chart 1-7) and others. Baseline recordings were obtained and hourly registrations of outcomes were undertaken. Confounding factors such as alcohol intoxication and vivid imagination was controlled by the means of alcohol breathalyzers and assessment of cerebral oxygenation by near infrared spectroscopy.. The vision of elves was induced in 10 out of 21 participants (48.6%) and was associated with male sex (p = 0.01), young age (p = 0.03) and increase in cerebral oxygenation (p = 0.04) but not with sweet woodruff (p = 0.83) or alcohol intoxication (p = 0.26). Participants were not capable of predicting the weather forecast (p = 0.55). Melancholia and nervousness were not relieved by St. John's wort, and obstipation could not be relieved by the intake of angelica.. Sweet woodruff, St. John's wort and angelica were unable to relieve relevant Christmas symptoms as proposed by a medieval doctor. Alcohol ingestion might have influenced results, and data should be interpreted in the light of these precautions.. none.. not applicable.

Topics: Alcoholic Intoxication; Depressive Disorder; Humans; Hypericum; Male; Phytotherapy

Hypericum perforatum (St John's wort) is an herbal plant that has antidepressant activity and contains ingredients such as flavonols derivatives, bioflavonoids, proanthocyanidins, xanthones, phloroglucinol, and naphthodianthrones. This study was aimed to test the effect of Hypericum perforatum on hot flashes, menopausal symptoms, and depression in postmenopausal women.. This randomized controlled study was conducted on 80 postmenopausal women aged 45-60 in Izeh, Iran.. Two groups received 270-330 μg of H. perforatum (n = 40) or placebo (n = 40) tablets three times a day for two months.. Data were collected using a socio-demographic questionnaire, the modified Kupperman index before the intervention and 2, 4, 6 and 8 weeks after intervention. The Hamilton Depression Rating Scale was used to gather data before the intervention and in the 8. Seventy women completed the study and five women from each group withdrew the study. The frequency and intensity of hot flashes and the score of Kupperman scale significantly decreased in the H. perforatum group compared to the control group (p < 0.001). In addition, the intensity of depression significantly decreased in the H. perforatum group compared to the control group. At the end of the study, 80% of women in the intervention group did not have depression compared to only 5.7% in the control group (p < 0.001).. Treatment with Hypericum perforatum is an efficient way of reducing hot flashes, menopausal symptoms, and depression in postmenopausal women.

Topics: Antidepressive Agents; Depression; Depressive Disorder; Double-Blind Method; Female; Hot Flashes; Humans; Hypericum; Iran; Middle Aged; Phytotherapy; Plant Extracts; Postmenopause

Emotional and behavioral problems in children and adolescents are no exception. To what extent a fixed plant extract combination is able to support children suffering from nervous agitation due to agitated depression among others for approximately 2 years has been investigated in a multicenter, prospective observational study (2008) with 115 children between 6 and 12 years. Assessments of the parents showed a distinct improvement in children who had attention problems, showed social withdrawal, and/or were anxious/depressive. Based on the physicians' assessment, 81.6-93.9% of the affected children had no or just mild symptoms at the end of observation concerning nine of thirteen evaluated symptoms such as depression, school/examination anxieties, further anxieties, sleeping problems, and different physical problems. Therapeutic success was not influenced by additional medication or therapies. The treatment was well tolerated. The used plant extracts have been gained from St. John's Wort herb, valerian root, and passionflower herb.

Topics: Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Child; Child Behavior Disorders; Comorbidity; Depressive Disorder; Drug Combinations; Female; Follow-Up Studies; Germany; Humans; Hypericum; Male; Passiflora; Phytotherapy; Plant Extracts; Psychomotor Agitation; Surveys and Questionnaires; Treatment Outcome; Valerian

St. John's Wort (Hypericum perforatum L.) is a useful medication in the treatment of mild to moderate depression. By reanalysis of the data obtained from a total of 154 patients, who responded in a randomised, multicentric, double-blind, placebo-controlled study, to 6 weeks of treatment for an episode of moderate depression with either 20 mg citalopram or 900 mg Hypericum extract STW 3-VI, the duration of response and occurrence of relapse/recurrence were evaluated. Duration of response and occurrence of relapse/recurrence was measured by re-evaluating the responders in a controlled-clinical trial (final score of ≤10 according to HAMD at the end of the clinical trial) according to the Hamilton Rating Scale for Depression (HAMD). In total, 30 (19.5%) of the 154 responders were diagnosed with a relapse. The numbers of patients with relapses were highest in the citalopram group (14 of 54), whereas patients who were treated with Hypericum extract STW 3-VI showed the lowest relapse rate (8/54); patients from the placebo group showed a relapse rate of 8/46. No difference in the severity of relapse could be observed. The duration of response was longest for the Hypericum group (1817 days), intermediate for the citalopram group (1755 days) and shortest for the placebo group (802 days). Hypericum extract STW 3-VI is more efficient in lowering the relapse and recurrence rates of responders, when compared to citalopram and placebo. In addition, duration of response was increased in the group treated with Hypericum extract STW 3-VI.

Topics: Adolescent; Adult; Aged; Citalopram; Depressive Disorder; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Young Adult

This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John's Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John's Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John's Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Citalopram; Depressive Disorder; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Quality of Life; Young Adult

Preliminary data suggest that hypericum extract LI160 is effective in atypical depression. Reported is the outcome of an 8-week double-blind, placebo-controlled, randomized trial of 600 mg LI160 vs. placebo in patients with vegetative features of atypical depression, i.e. hyperphagia or hypersomnia. One-hundred (100) patients with mild and 100 patients with moderate severity of a major depression according to ICD-10 were randomized. Patients needed to meet a score of 2 in at least one of the items 22-26 of the Hamilton-Depression-Rating-Scale (HAM-D) 28-item version and episode duration of at least 3 months. The primary outcome variable was the relative change of the HAM-D(17) from Baseline. Secondary outcome variables were the depression sub-score of the Patient Health Questionnaire (PHQ-9), the Clinical Global Impression (CGI), a patient's satisfaction scale, the Hamilton-Anxiety-Scale (HAM-A) and the sum score of atypical vegetative symptoms of the HAM-D(28). The percentage reduction of the HAM-D(17) for LI160 compared to placebo approached statistical significance (p=0.051) in the Full Analysis Set (FAS)-population. Using the conventional criterion of the absolute reduction of the HAM-D(17) significance was achieved (p<0.05). No significant benefit could be observed for the sum score of the atypical vegetative items of the HAM-D(28;) however, the sum score of the hypersomnia items (items 22-24) showed a significant superiority for LI160. The HAM-A, PHQ-9, and CGI-I scales demonstrated superiority of LI160 (p<0.01). Confining the analysis to moderately depressed patients, a highly significant benefit for the primary outcome variable was revealed. The study supports the beneficial effect of LI160 in depression with atypical features and the validity of the definition of atypical depression on the basis of reversed vegetative signs. Further, it identifies the PHQ-9 as a useful outcome variable in this population.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depression; Depressive Disorder; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Plant Extracts; Psychiatric Status Rating Scales; Statistics, Nonparametric; Time Factors; Young Adult

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.

Topics: Adult; Antidepressive Agents; Body Mass Index; Depressive Disorder; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts

Patients suffering from an acute episode of mild to moderate major depression and who had been treated successfully with Hypericum perforatum extract WS 5570 in doses of 600 mg/day or 1200 mg/day or with placebo for 6 weeks in a multi-centre, double-blind, randomized clinical trial, were asked to take part in a continuation treatment. Those participants with a HAMD total score decrease > or =50% during acute treatment were eligible for 4 months of double-blind continuation treatment with the same dose regimen. In total, 69, 68 and 24 (WS 5570 600 mg/day, 1200 mg/day and placebo) patients entered continuation treatment. Both WS 5570 groups showed an additional slight decrease of the HAMD total score by 0.8 (600 mg WS 5570/day) and 0.4 (1200 mg WS 5570/day) points during treatment phase, while patients in the placebo group deteriorated by 2.1 points. The incidence of adverse events was low in all therapy groups.

Topics: Adolescent; Adult; Aged; Depressive Disorder; Female; Follow-Up Studies; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Placebos; Plant Extracts; Time Factors; Treatment Outcome

Hypericum perforatum has demonstrated antidepressant efficacy when compared to placebo, but comparisons with other antidepressants remain controversial. We assessed the efficacy and safety of Hypericum perforatum in comparison with fluoxetine, in a 8-week double-blind trial in patients with mild to moderate depression.. Seventy-two outpatients were randomly assigned to receive Hypericum perforatum 900 mg/day, fluoxetine 20 mg/day or placebo. Efficacy measures included the HAM-D21 scale, the Montgomery-Asberg Rating Scale, and the Clinical Global Impression. Safety was assessed with the UKU Side Effect Rating Scale.. Intention-to-treat analysis showed no differences between the mean scores of the three groups. In the analyses of observed cases, patients receiving Hypericum perforatum had the lowest remission rates (12%, p = 0.016) compared to fluoxetine (34.6%) and placebo (45%).. Hypericum perforatum was less efficacious than both fluoxetine and placebo. Both drugs were safe and well-tolerated. Larger trials are needed for definite conclusions.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Brazil; Depressive Disorder; Double-Blind Method; Female; Fluoxetine; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Placebo Effect; Plant Extracts; Treatment Outcome

The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses.. The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS 5570 600 mg/day, 127 to WS 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination.. After 6 weeks of treatment, mean +/- standard deviation decreases in HAM-D total scores of 11.6 +/- 6.4, 10.8 +/- 7.3, and 6.0 +/- 8.1 points were observed for the WS 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS 5570 groups were statistically superior to placebo. Significantly more patients in the WS 5570 treatment groups than in the placebo group showed treatment response and remission. WS 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS 5570 1200 mg/day group than the WS 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations.. Hypericum perforatum extract WS 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS 5570 groups for the treatment of mild to moderate major depression.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Severity of Illness Index

The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression.. A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period.. After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as "good" or "very good.". The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.

Topics: Adolescent; Adult; Aged; Depressive Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Humans; Hypericum; International Classification of Diseases; Male; Middle Aged; Phytotherapy; Selective Serotonin Reuptake Inhibitors; Sertraline; Severity of Illness Index; Time

St. John's wort extract is widely used and advertised as a "natural antidepressant" lacking autonomic side effects. This randomized, double-blind, placebo-controlled study compared the effects of St. John's wort extract on autonomic responses of blood vessels and sweat glands with those of amitriptyline and placebo. A randomized, double-blind, crossover study was performed in healthy male volunteers aged 22 to 31 years (25 +/- 3 years; mean +/- SD) years. Subjects orally received capsules with 255 to 285 mg St. John's wort extract (900 microg hypericin content), 25 mg amitriptyline, and placebo 3 times daily for periods of 14 days each with at least 14 days between. Vasoconstrictory response of cutaneous blood flow (VR) and skin conductance response (SR) following a single deep inspiration were employed as parameters of autonomic function. St. John's wort extract had no effect on VR and SR. In contrast, SR was diminished and the dilation phase of VR was prolonged following multiple dosing with amitriptyline (P < 0.05). Decreased electrodermal reactivity observed with amitriptyline reflects inhibition of acetylcholine at peripheral m3-cholinoreceptors, whereas prolongation of VR induced by the tricyclic drug may be due to sustained activation of central and/or peripheral sympathetic neurons.

Topics: Administration, Oral; Adult; Amitriptyline; Antidepressive Agents; Autonomic Nervous System; Blood Vessels; Capsules; Cross-Over Studies; Depressive Disorder; Drug Administration Schedule; Galvanic Skin Response; Germany; Humans; Hypericum; Male; Phytotherapy; Plant Extracts; Regional Blood Flow; Skin; Sweat Glands

A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo.. Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John's wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John's wort or placebo were treated with an antidepressant for 24 weeks.. During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John's wort extract, 5 (29.4%) relapsed.. The subjects who did not respond to St. John's wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.

Topics: Adult; Ambulatory Care; Antidepressive Agents; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypericum; Male; Phytotherapy; Placebos; Plant Extracts; Psychiatric Status Rating Scales; Regression Analysis; Treatment Outcome

St. John's wort, a popular over-the-counter drug for treatment of depression, might reduce concentrations of drugs such as cyclosporin and indinavir and lead to drug resistance and treatment failure. No studies as yet have examined its influence on methadone plasma levels. The trough methadone plasma levels were measured in four patients (2 males, median age: 31 years; range 19 - 40 years) in methadone maintenance treatment just before the introduction of St. John's wort (900 mg/d) and after a median period of 31-day treatment (range 14 - 47). The study was proposed to addict patients about to start an antidepressant therapy. Introduction of St. John's wort resulted in a strong reduction of (R,S)-methadone concentration-to-dose ratios in the four median patients included, with a median decrease to 47 % of the original concentration (range: 19 % - 60 % of the original concentration). Two patients reported symptoms that suggested a withdrawal syndrome. Thus, prescription of St. John's wort might decrease methadone blood levels and induce withdrawal symptoms which, if not correctly identified and handled (by changing the antidepressant or by increasing the methadone dose), might cause unnecessary discomfort to the patient, lead to resumption of illicit drug uses, or be a risk factor for discontinuation of the methadone or antidepressant treatment.

Topics: Adult; Analgesics, Opioid; Depressive Disorder; Drug Interactions; Drug Therapy, Combination; Humans; Hypericum; Male; Methadone; Plant Preparations; Substance-Related Disorders

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.. 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.. 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.. H. perforatum extract WS 5570 was found to be safe and more effective than placebo for the treatment of mild to moderate depression.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Placebos; Plant Extracts; Psychiatric Status Rating Scales; Recurrence; Severity of Illness Index; Treatment Outcome

Topics: Depressive Disorder; Double-Blind Method; Follow-Up Studies; Humans; Hypericum; Phytotherapy; Plant Extracts; Psychiatric Status Rating Scales; Secondary Prevention; Sertraline; Treatment Outcome

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.. Double-blind, randomized 12-week trial.. Community-based offices of 12 family physicians practising in greater Montreal, Que.. Eighty-seven men and women with major depression and an initial score of > or = 16 on the Hamilton Rating Scale for Depression (Ham-D).. 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.. Changes from baseline in Ham-D and BDI scores and self-reported side effects.. 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.. The more benign side effects of SJW make it a good first choice for this patient population.

Topics: Adult; Analysis of Variance; Antidepressive Agents; Depressive Disorder; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Sertraline

We have investigated the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS5572 in a double-blind, placebo-controlled multicenter clinical trial. 72 patients (WS 5572: 37, placebo: 35) with a diagnosis of mild to moderate major depressive disorder (according to DSM-IV criteria) were randomized in 42 days of treatment with either 300 mg WS5572 t.i.d. or placebo. The primary efficacy variable was the change of the 17-item Hamilton Depression Scale (HAMD) total score between baseline and double-blind treatment. The study was conducted with an adaptive interim analysis, which led to early stopping because convincing treatment efficacy could already be demonstrated. Group differences in favor of WS 5572 were descriptively apparent as early as day 7 of randomized treatment and were statistically significant at days 28 (p = 0.011) and day 42 (p < 0.001). Between baseline and treatment end, the HAMD total score decreased from 19.7 +/- 3.4 to 8.9 +/- 4.3 points in the Hypericum group and from 20.1 +/- 2.6 to 14.4 +/- 6.8 points in the placebo group (mean +/- SD). Responder rates were consistently higher in the Hypericum group. Comparable group differences in favor of WS 5572 were also found for von Zerssen's Depression Scale (D-S; self-rating), Clinical Global Impressions (CGI) and a global patient's self-assessment (GPA). Tolerability was very good in both groups, with no adverse drug reactions and no clinically relevant changes in safety parameters. The results indicate that Hypericum extract WS 5572 is an effective and well-tolerated drug for the treatment of mild to moderate major depressive disorder.

Topics: Adult; Aged; Depressive Disorder; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Multicenter Studies as Topic; Phytotherapy; Plant Extracts; Psychiatric Status Rating Scales

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.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Anxiety; Depressive Disorder; Female; Fluoxetine; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Severity of Illness Index

In this multi-centre study, the effectiveness and tolerability of an extract of herba hyperici WS 5572 were examined. The total of 2,166 participating patients, all suffering from mild to moderate depression, were prescribed to take 600 mg (one tablet) or 1,200 mg (two tablets) daily. Four-hundred-forty-six general practitioners, psychiatrists and neurologists conducted the survey. Three quarters of the participating patients were female at an average age of 50 years. Most of the patients suffered from a depression which was diagnosed for the first time. Approximately in one third of the patients, a recurrent depression was diagnosed.. The average severity of the depression was "moderate" (basing on CGI; Clinical Global Impression Scale) at the beginning of the survey and was reduced to less than "mild" after an average observation time of seven weeks. 83.7% patients (600 mg) and 88.6% (1,200 mg) responded respectively. During this observation period, an improvement in symptoms, measured in 17 items, was of clinical relevance. The treating physicians described the drug tolerance as being good or very good for 99% in all cases. This observation was confirmed by adverse drug reactions, which amounted to 0.41%. The low ratio of adverse drug reactions of 0.41% confirmed the physicians' judgement.. The results obtained from this observational study were similar to those of an equally designed observation performed in 1998, where St. John's wort was observed in a dosage of 300 mg per tablet (standard dosage 3 x 300 mg/d). This is a good proof of the effectiveness and the tolerability of this drug in patients who are suffering from mild and moderate depressive episodes.

Topics: Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Treatment Outcome

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.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Double-Blind Method; Female; Fluoxetine; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Plants, Medicinal; Treatment Outcome

In clinical trials of antidepressant treatments, a depression rating score is usually measured at several points of time for each patient. We propose an approach to fit data from this type of clinical trial using an exponential mixed-effects model. Compared to previous proposals, this approach has the advantage that individual recovery curves are fitted rather than curves of means. Furthermore, no artificial fixing of model parameters is needed as in other approaches. The flexibility of the proposed model is shown for various situations. The approach is illustrated by an example from a placebo-controlled study for the treatment of depression with St. John's Wort (Hypericum perforatum).

Topics: Antidepressive Agents; Depressive Disorder; Double-Blind Method; Humans; Hypericum; Mathematical Computing; Models, Statistical; Personality Assessment; Phytotherapy; Plants, Medicinal; Psychometrics; Reproducibility of Results; Treatment Outcome

To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.. Randomised, double blind, multicentre, parallel group trial for 8 weeks.. Trained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.. 263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32. 1 and F33.1.. 1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.. Change from baseline score on the 17 item version of the Hamilton depression scale, the Hamilton anxiety scale, the clinical global impressions scale, Zung's self rating depression scale, and SF-36, and adverse events profile.. Hypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean -15.4 (SD 8.1), -12.1 (7.4), and -14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).. At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.

Topics: Adult; Antidepressive Agents, Tricyclic; Depressive Disorder; Double-Blind Method; Female; Humans; Hypericum; Imipramine; Male; Middle Aged; Patient Compliance; Phytotherapy; Plants, Medicinal; Quality of Life; Treatment Outcome

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female outpatients suffering from mild or moderate depression according to DSM-IV criteria. Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3 x 1 tablets of either placebo, Hypericum extract WS 5573 (300 mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for the two Hypericum preparations was identical, so that they differed only in their hyperforin content. Efficacy regarding depressive symptoms was assessed on days 0, 7, 14, 28, and 42, using the Hamilton Rating Scale for Depression (HAMD, 17-item version) and the Depression Self-Rating Scale (D-S) according to von Zerssen. In addition, the severity of illness was also rated by the investigators on days 0 and 42 using the Clinical Global Impression (CGI) scale. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 +/- 4.6 points; mean +/- SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 +/- 6.1 points) and the placebo group (7.9 +/- 5.2 points). As regards the change in the HAMD total score between day 0 and treatment end and its relationship to the hyperforin dose, a significant monotonic trend was demonstrated in the Jonckheere-Terpstra test (p = 0.017). In pairwise comparisons, WS 5572 (5% hyperforin) was superior to placebo in alleviating depressive symptoms according to HAMD reduction (Mann-Whitney U-test: p = 0.004), whereas the clinical effects of WS 5573 (0.5% hyperforin) and placebo were descriptively comparable. These results show that the therapeutic effect of St. John's Wort in mild to moderate depression depends on its hyperforin content.

Topics: Antidepressive Agents; Bridged Bicyclo Compounds; Depressive Disorder; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Perylene; Phloroglucinol; Plant Extracts; Plants, Medicinal; Quercetin; Terpenes; Xanthenes

The special extract of St. John's wort, LI 160, exhibited a superior antidepressant efficacy compared to placebo in several controlled trials. Two further trials demonstrated a similar reduction of depressive symptomatology under LI 160 compared to tricyclics. All these trials were performed in mildly to moderately depressed patients. The present investigation was a randomized, controlled, multicentre, 6-week trial comparing 1800 mg LI 160/die to 150 mg imipramine/die in severely depressed patients according to ICD-10. The main efficacy parameter, a reduction of the total score of the Hamilton Depression Scale, proved both treatment regimens very effective at the end of the 6 week treatment period (mean values 25.3 to 14.5 in the LI 160 group and 26.1 to 13.6 in the imipramine group), but not statistically equivalent within a a-priori defined 25% interval of deviation. The analysis of subgroups with more than a 33% and 50% reduction of the HAMD total score justified the assumption of equivalence within a 25% deviation interval. This view was also supported by the global efficacy ratings from patients and investigators. Regarding adverse events, the nonrejection of the nonequivalence hypothesis denotes a superiority of the herbal antidepressant. These main result indicate that LI 160 might be a treatment alternative to the synthetic tricyclic antidepressant imipramine in the majority of severe forms of depressions. However, more studies of this type must be performed before a stronger recommendation can be made.

Topics: Adult; Aged; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depressive Disorder; Double-Blind Method; Female; Humans; Hypericum; Imipramine; Male; Middle Aged; Perylene; Plants, Medicinal; Psychiatric Status Rating Scales; Quercetin; Xanthenes

The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a randomized, double-blind, multicenter treatment study of 209 patients suffering from depression. ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine. At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings. In the first ECG analysis comparing high dose hypericum extract with imipramine, a prolongation of the conduction intervals PR, QRS and QTc was found for imipramine. In contrast, a small acceleration of conduction was seen for the high-dose hypericum extract. The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract. It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract. The reduction in pathological ECG features after treatment with hypericum extract may have resulted mainly from the change of medication, probably tricyclics, to hypericum extract. Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients, high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants.

Topics: Adult; Aged; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depressive Disorder; Double-Blind Method; Electrocardiography; Female; Heart Conduction System; Humans; Hypericum; Imipramine; Male; Middle Aged; Perylene; Plants, Medicinal; Psychiatric Status Rating Scales; Quercetin; Xanthenes

Topics: Aged; Depressive Disorder; Diagnosis, Differential; Female; Humans; Hypericum; Migraine with Aura; Phytotherapy; Plant Extracts; Vertigo

The study investigated the use of serotonergic antidepressants (SSRIs: selective serotonin reuptake inhibitors; SNRIs: serotonin-norepinephrine reuptake inhibitors) and St John's wort in a large NSW-based community sample, and sought to identify a potentially dangerous concomitant use of these medications.. Cross-sectional data from 266,848 participants from the '45 and Up' study were used. The questionnaire captures self-reported treatment for depression or anxiety and antidepressant medications in the last four weeks.. 5.8% of participants received treatment for depression or anxiety, with 4.7% taking an SSRI and 1.3% an SNRI. St John's wort was taken by 0.3% of the participants. Use of SSRIs and SNRIs was reported more frequently by females than males (respectively, 64.1% vs 35.9%, 66.9% vs 33.1%). The gender difference was even more pronounced for St John's wort (75.6% vs. 24.4%). Use of antidepressants decreased after the age of 65 years. One hundred and forty people reported concurrent use of an SSRI and an SNRI, and 11 people of an SSRI with St John's wort.. Around 7% of the study population aged 45-65 years reported the use of SSRIs or SNRIs, decreasing to 5% above 70 years of age. It is of concern that some individuals used an SSRI concurrently with St John's wort.

Topics: Age Distribution; Aged; Antidepressive Agents; Anxiety; Australia; Cohort Studies; Depressive Disorder; Drug Interactions; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Preparations; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Sex Distribution; Surveys and Questionnaires

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. Clinical controlled trials have found St. John's wort to be as effective as antidepressants in the treatment of mild to moderate depression. The objective of this study was to develop a model to assess the cost-effectiveness of St. John's wort based on this evidence.. A Markov model was constructed to estimate health and economic impacts of St. John's wort versus antidepressants. Outcomes were treatment costs, quality-adjusted life years (QALYs) and Net Monetary Benefits (NMB). Probabilistic analyses were conducted on key model parameters.. The average NMB across 5000 simulations identified St. John's wort as the strategy with the highest net benefit. The total cost savings for SJW were $359.66 and $202.56 per individual for venlafaxine and sertraline respectively, with a gain of 0.08 to 0.12 QALYs over the 72 weeks of the model.. A lack of direct comparative clinical trial data comparing SJW to venlafaxine and limited data with sertraline as a comparator was a major limitation.. In this model, St. John's wort was shown to be a cost-effective alternative to generic antidepressants. Patients are more likely to receive treatment for a duration consistent with professional guidelines for treatment of major depression due to reduced incidence of adverse effects, improving outcomes. This represents an important option in the treatment of Major Depressive Disorder.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Australia; Cost-Benefit Analysis; Cyclohexanols; Depressive Disorder; Depressive Disorder, Major; Humans; Hypericum; Markov Chains; Middle Aged; Models, Economic; Phytotherapy; Plant Preparations; Sertraline; Severity of Illness Index; Treatment Outcome; Venlafaxine Hydrochloride; Young Adult

The protective effects of St John's Wort extract (SJ), ginsenosides (GS), and clomipramine (CPM) on chronic unpredictable mild stress (CUMS)-induced depression in rats were investigated by using a combination of behavioral assessments and metabonomics. Metabonomic analyses were performed using gas chromatography/mass spectrometry in conjunction with multivariate and univariate statistical analyses. During and at the end point of the chronic stress experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured. Changes in these parameters reflected characteristic phenotypes of depression in rats. Metabonomic analysis of serum, urine, and brain tissue revealed that CPM and SJ mainly attenuated the alteration of monoamine neurotransmitter metabolites, while GS affected both excitatory/inhibitory amino acids and monoamine neurotransmitter metabolites. GS also attenuated the stress-induced alterations in cerebrum and peripheral metabolites to a greater extent than CPM and SJ. These results provide important mechanistic insights into the protective effects of GS against CUMS-induced depression and metabolic dysfunction.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Antidepressive Agents; Behavior, Animal; Body Weight; Clomipramine; Depressive Disorder; Disease Models, Animal; Food Deprivation; Gas Chromatography-Mass Spectrometry; Ginsenosides; Hypericum; Male; Metabolome; Metabolomics; Multivariate Analysis; Phenotype; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Spleen; Stress, Psychological; Sucrose; Swimming; Thymus Gland

According to European law a comprehensive patient information leaflet (PIL) has to accompany all medicines. In this study we examined the uniformity, adequacy and balance of information contained in UK antidepressant PILs.. We studied antidepressant PILs available in the Electronic Medicines Compendium and subjected each to a content analysis. Words were assessed as being positive, negative or neutral.. Forty-two PILs concerning 21 different antidepressants and 23 pharmaceutical companies were studied. PILs presented information about side effects in a strikingly heterogeneous way, making it difficult for patients to find the required information. Half the PILs provided no information about how the antidepressant is thought to work. Over 90% stated the antidepressant would take 2-4 weeks to work, although a few PILs indicated earlier onset of improvement. Not all PILs warned about discontinuation syndrome and advice about alcohol was generally that it was prohibited. Almost half of PILs made no mention of St John's wort and its potential for interaction with the antidepressant. Two-thirds of PILs provided no information about the likely duration of treatment. PILs contained far more words judged to be negative rather than positive or neutral.. Data were extracted by a single researcher, although inter-rater agreement was high.. Further guidance and tightening of the approval process for PILs are needed to ensure they are more standardised in content and contain more information that is wanted by and is useful to patients.

Topics: Alcohol Drinking; Antidepressive Agents; Depressive Disorder; Drug Labeling; Health Services Needs and Demand; Humans; Hypericum; Pamphlets; Patient Education as Topic; United Kingdom

Health consumers are increasingly using the Internet to access information about health care, to self-diagnose, and to purchase medication. The use of the Internet to purchase herbal products is of particular interest because of the high level of consumer expenditure on herbal medicines, and the misperception by some consumers that herbal products are natural, and thus absent of any contraindications, drug interactions and adverse effects. It is possible that consumers may purchase herbal medicines via the Internet without consulting health professionals and therefore, use these medicines in an unsafe manner.. To examine the quality of e-commerce websites that sell herbal products; specifically, websites where St. John's wort (Hypericum perforatum) can be purchased.. Cross-sectional survey of 54 selected websites, including online pharmacies, online health food stores and manufacturers of herbal medicines.. A modified version of the DISCERN instrument was used to assess the quality of websites.. The majority of websites rated poorly with a concerning lack of information about the interaction between hypericum and warfarin, anti-depressants and oral contraceptives. Most sites also failed to provide sufficient information about the contraindications and adverse effects of hypericum treatment.. The results of this study strongly support the need for improved consumer education about herbal medicine, as well as the application of more stringent standards to websites that sell medications.

Topics: Antidepressive Agents; Commerce; Consumer Health Information; Contraindications; Cross-Sectional Studies; Depressive Disorder; Herb-Drug Interactions; Humans; Hypericum; Internet; Phytotherapy; Plant Extracts

Topics: Combined Modality Therapy; Depressive Disorder; Female; Humans; Hypericum; Middle Aged; Naturopathy; Phytotherapy; Plant Extracts

Topics: Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; General Practice; Germany; Humans; Hypericum; Medication Adherence; Phytotherapy; Plant Preparations

Topics: 5-alpha Reductase Inhibitors; Cytochrome P-450 CYP3A; Depressive Disorder; Drug Interactions; Enzyme Activation; Finasteride; Humans; Hypericum; Male; Phytotherapy; Plant Extracts; Prostate-Specific Antigen; Prostatic Hyperplasia

Topics: Combined Modality Therapy; Complementary Therapies; Contraindications; Depression; Depressive Disorder; Exercise; Germany; Humans; Hypericum; Phototherapy; Plant Extracts

The use of complementary and alternative medicines (CAM) has increased among patients with psychiatric disorders over recent decades. Therefore, clinicians must inquire and be knowledgeable about the use of CAM therapies, not only to give their patients accurate and up-to-date information but also to know when to appropriately prescribe CAM therapies to patients. Of the available CAMs, omega-3 fatty acids, folate, SAM-e, and St John's wort are reviewed.

Topics: Antidepressive Agents; Complementary Therapies; Depressive Disorder; Fatty Acids, Omega-3; Folic Acid; Humans; Hypericum; Phytotherapy; S-Adenosylmethionine

Biological treatment procedures are based on evidence-based guidelines. According to all of them, a correct diagnosis of depression is required before starting therapy. Within recent years many different types of antidepressants have been introduced to the pharmacotherapeutic armamentarium. The "newer" antidepressants were developed with a view to reduced side effects. However, the classes of antidepressants currently available differ little in their antidepressant efficacy, thus, all producing treatment responses of 50 - 75 %. Therefore, the selection of a particular antidepressant for the individual patient depends on various factors: patient's prior experience with medication, concurrent medical conditions that may be worsened by selected antidepressants, concomitant use of non-psychiatric medications that may lead to negative drug-drug interactions, a drug's short and long-term side effects, physician's experience with the medication and patient's history of adherence to medication. Importantly, if the patient does not show any improvement after two to four weeks of treatment with an antidepressant dose at the upper level of the standard dose, it becomes less likely that he will respond to this particular medication later. When a partial or non-response is present, several therapeutic options are available: (1) combining two antidepressants from different classes, (2) switch to new antidepressant from a different or the same pharmacological class and (3) augmentation strategies. For patients who are reluctant to take traditional antidepressants, herbal remedies such as hypericum perforatum (St. John's Wort) provide an alternative for treatment of mild to moderate depression. Besides pharmacological treatment options non pharmacological biological interventions are available. Electroconvulsive therapy and partial sleep deprivation are very effective in the treatment of acute depression. Especially for seasonal affective disorders light therapy is a well established treatment alternative. Further new biological treatment approaches such as rapid transcranial magnetic stimulation (rTMS) showed inconsistent results.

Topics: Antidepressive Agents; Combined Modality Therapy; Depressive Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Hypericum; Long-Term Care; Phytotherapy; Plant Extracts; Psychotherapy; Secondary Prevention

Herbal preparations for depression are often preferred over pharmaceutical drugs because they are available without prescription and because they are commonly assumed to be safe. St. John's wort (SJW) is one of the best-known and best-selling herbal therapies for depression. Meta-analyses of randomized controlled trials of SJW for major depression suggest that SJW is superior to placebo, is similarly effective compared with conventional antidepressant drugs, and tends to have fewer side effects compared with antidepressant agents, but there is a large degree of heterogeneity among the placebo-controlled studies, and trials from German-speaking countries tend to report more favorable findings. A small number of studies suggest SJW is safe to use during pregnancy and breastfeeding. Although SJW is relatively well tolerated, it is prone to many important drug-drug interactions.

Topics: Breast Feeding; Depressive Disorder; Depressive Disorder, Major; Female; Herb-Drug Interactions; Humans; Hypericum; Phytotherapy; Plant Preparations; Pregnancy

Topics: Depressive Disorder; Evidence-Based Medicine; Humans; Hypericum; Phytotherapy; Plant Extracts; Reproducibility of Results

Topics: Antidepressive Agents; Depressive Disorder; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Folic Acid; Humans; Hypericum; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Treatment Outcome

The present contribution describes the history of the Cochrane review on St. John's wort (hypericum perforatum L.) for depression. Work for the first version started in 1993, the year that saw the official foundation of the Cochrane Collaboration, but 3 years before a pertinent Cochrane review group was established. After the registration of the Collaborative Review Group for Depression, Anxiety and Neuroses (CCDAN) and the publication of a first print version of the review that included 23 trials in 1996 the first Cochrane version with 27 trials became available in 1998. Updates were completed in 2005 (37 included trials) and 2008 (29 trials). Due to changes in selection criteria and review methods the resources needed to complete the 2005 and 2008 updates were similar to those for the first version in 1996. Only one trial included in the 1996 version is still part of the 2008 version. Despite the large number of available trials and improvements in review methodology the current evidence is more difficult to interpret than in 1996.

Topics: Clinical Trials as Topic; Depressive Disorder; Germany; History, 20th Century; Humans; Hypericum; Organizations; Phytotherapy; Placebos; Plant Extracts; Plants, Medicinal

To examine the association between access to conventional health care and the use of St. John's wort among adults who report depressive symptoms.. Logistic secondary analysis of the Complementary and Alternative Medicine Supplement to the 2002 National Health Interview Survey (NHIS).. Adults who report depressive symptoms and used St. John's wort (n = 246) were compared to nonusers with depressive symptoms (n = 5,111).. After controlling for various sociodemographic and socioeconomic factors, depressed adults who could not afford needed medical care due to cost were nearly two times (AOR 1.92, 95% CI 1.38-2.67) more likely to use St. John's wort than those who could afford conventional medical care. Higher income, education, and health status were also positively associated with the use of St. John's wort.. The growing use of complementary and alternative therapies in the US is widely interpreted as evidence of changing consumer tastes and dissatisfaction with conventional medical treatment for chronic conditions like depression. However, the rising costs of conventional therapies and diminishing access to health insurance may also play a role.

Topics: Adolescent; Adult; Aged; Consumer Behavior; Costs and Cost Analysis; Depression; Depressive Disorder; Educational Status; Female; Health Services Accessibility; Health Status; Health Surveys; Humans; Hypericum; Income; Male; Middle Aged; Patient Acceptance of Health Care; Phytotherapy; Plant Extracts; United States; Young Adult

Depressive disorders are frequent. They are frequently unrecognised or sufferers use self help or self medication, e.g. with St. John's wort (SJW), instead of seeking professional help. The purpose of this study is to examine patients who buy SJW for the treatment of depression.. In pharmacies from all over Germany customers who bought SJW and the pharmacists were asked to fill in a questionnaire on the cause for buying SJW, their health status and the type of counselling they received.. 588 individuals were included, 293 purchased SJW as an OTC preparation, 230 had a prescription (65 missing answers). The majority in both groups were women (78.8% in OTC group, 74.3% in prescription group. Self medication patients were significantly younger. Subjects with a prescription took SJW longer (26.99+/-26.84 vs. 15.25+/-20.84 months). Both groups did not differ in self rated symptoms of depression (severity of depression, anxiety, endurance).. No standardized interviews were used to establish the diagnosis of depression.. Patients who buy SJW for self medication report pronounced and persistent depressive symptoms. As this is a large group of patients they should get more attention in research. Pharmacists are the only professionals who come in contact with these patients and should therefore be considered as an important group of carers.

Topics: Attitude to Health; Depressive Disorder; Drug Prescriptions; Female; Germany; Health Status; Humans; Hypericum; Male; Middle Aged; Nonprescription Drugs; Pharmacies; Pharmacists; Phytotherapy; Plant Preparations; Self Medication; Severity of Illness Index; Surveys and Questionnaires

Topics: Depressive Disorder; Humans; Hypericum; Plant Extracts

Herbal preparations for depression, such as St. John's wort, are often preferred over pharmaceutical preparations by mothers and midwives after childbirth because these preparations are available to patients as over-the-counter "natural" treatments and are popularly assumed to be safe. The only existing report on St. John's wort excretion into human milk showed that only 1 active component (hyperforin) was detectable in breast milk, but was not detectable in the infants' plasma. Another report found more cases of minor problems in infants breast-fed by women taking St. John's wort. However, significance was reached only in comparison with disease-matched women (p<.01), not healthy controls (p=.20).. Five mothers who were taking 300 mg of St. John's wort 3 times daily (LI 160 [Jarsin], Lichtwer Pharma GmbH; Berlin, Germany) and their breastfed infants were assessed. Thirty-six breast milk samples (foremilk and hindmilk collected during an 18-hour period) and 5 mothers' and 2 infants' plasma samples were analyzed for hyperforin levels by tandem mass spectrometry (LC/MS/MS; limit of quantification=0.1 ng/mL). Data were gathered from January 2001 to February 2002.. Hyperforin is excreted into breast milk at low levels. However, the compound was at the limit of quantification in the 2 infants' plasma samples (0.1 ng/mL). Milk/plasma ratios ranged from 0.04 to 0.13. The relative infant doses of 0.9% to 2.5% indicate that infant exposure to hyperforin through milk is comparable to levels reported in most studies assessing anti-depressants or neuroleptics. No side effects were seen in the mothers or infants.. These results add to the evidence of the relative safety of St. John's wort while breast-feeding found in previous observational studies.

Topics: Adult; Breast Feeding; Bridged Bicyclo Compounds; Depressive Disorder; Female; Humans; Hypericum; Infant; Mass Spectrometry; Maternal Exposure; Maternal-Fetal Exchange; Milk, Human; Phloroglucinol; Phytotherapy; Plant Preparations; Pregnancy; Terpenes

Extracts of the plant St. John's Wort, Hypericum perforatum, are effective for treatment of mild depression. It has been hypothesised that H. perforatum may be acting on the circadian timing system either directly or via a photosensitising action to produce changes in mood. Two experiments were conducted to test these hypotheses. Under constant dark (Experiment 1) or low constant light (Experiment 2) rats were permitted to free-run. Rats were then treated with a 'high' (616mg/kg/day; n = 8 per experiment) or 'low' (308 mg/kg/day; n = 8 per experiment) dose of H. perforatum or a control solution (n = 8 per experiment) in drinking water, and circadian locomotor rhythms examined for alterations of period. A minor shortening of mean period (2.4 min) was observed on cessation of H. perforatum treatment in the low-dose group in Experiment 2, and was considered to be a measurement artifact and of no clinical value. Otherwise, no significant differences in free-running period between treatment groups were observed in either study, indicating that H. perforatum has no direct or photosensitising effect on the mammalian circadian system. These results suggest that the antidepressant action of H. perforatum is not mediated by a circadian mechanism.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Circadian Rhythm; Depressive Disorder; Hypericum; Light; Male; Phytotherapy; Plant Extracts; Rats; Rats, Long-Evans

Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Double-Blind Method; Humans; Hypericum; Nonprescription Drugs; Paroxetine; Phytotherapy; Randomized Controlled Trials as Topic

Topics: Antidepressive Agents; Child; Combined Modality Therapy; Depressive Disorder; Humans; Hypericum; Psychotherapy

Topics: Depressive Disorder; Germany; Humans; Hypericum; Insurance Coverage; Insurance, Pharmaceutical Services; National Health Programs; Nonprescription Drugs; Phytotherapy; Plant Extracts

Aim of the post-marketing surveillance was to investigate if the single-dose-administration of highlydosed St. John's Wort extract improves quality of life of patients with depressive symptoms.. During a twelve week treatment 4337 patients with depression were observed. Mental and physical state of health were documented using the SF-12-sumscore as a measure for quality of life. Further efficacy and tolerability was rated by physician and patient. Adverse drug reactions were documented as well.. During therapy the mental and the physical SF-12-sumscore had improved significantly. At the end ofthe observation the values rise up to the norm. About 80 percent of the physicians and patients marked the drug's efficacy as good or very good. Tolerability was assessed as good or very good in more than 95%.. A post-marketing surveillance including 4337 depressive patients shows that a single-dose therapy with highly dosed St. John's Wort extract causes to improve significantly the quality of life. The patients suffered from mild to moderate depression.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Female; Humans; Hypericum; Male; Middle Aged; Personality Inventory; Phytotherapy; Plant Extracts; Pregnancy; Product Surveillance, Postmarketing; Quality of Life; Retrospective Studies

A 23-year-old patient of mine has been taking St John's wort for postpartum depression for about 2 years. She is now planning her second pregnancy. Is she or her fetus at risk if she continues to take the herbal therapy?. Despite the widespread availability and use of St John's wort and extensive research on the herb, there are almost no data on reproductive safety. At this stage, therefore, St John's wort cannot be recommended as safe therapy during pregnancy.

Topics: Adult; Contraindications; Depressive Disorder; Female; Humans; Hypericum; Phytotherapy; Plant Extracts; Pregnancy; Pregnancy Complications

Topics: Antidepressive Agents; Depressive Disorder; Drug Administration Schedule; Humans; Hypericum; Long-Term Care; Phytotherapy; Plant Extracts; Secondary Prevention; Treatment Outcome

Topics: Depressive Disorder; Humans; Hypericum; Plant Extracts

Topics: Depressive Disorder; Dose-Response Relationship, Drug; Humans; Hypericum; Patient Acceptance of Health Care; Phytotherapy; Plant Extracts; Secondary Prevention; Treatment Refusal

We examined the safety of St. John's wort to nursing mothers and their infants.. A prospective, observational, cohort study was conducted. Thirty-three breastfeeding women receiving St. John's wort (Group 1) who contacted our teratogen/toxicant counseling service regarding the safety of St. John's wort during breastfeeding were followed up between May 1999 and April 2001. These women were compared with 101 disease-matched (Group 2) and 33 age- and parity-matched nondisease controls (Group 3). Information collected included maternal and neonatal demographics, breastfeeding duration, use of St. John's wort, maternal and infant adverse events, infant weight over the first year of life, and whether or not the mother experienced a decrease in lactation.. There were no statistically significant differences found in maternal or infant demographics or maternal adverse events. Whereas only 1 infant each in Groups 2 and 3 was reported to be colicky, there were 2 cases of "colic," 2 of "drowsiness," and 1 of "lethargy" in Group 1 (p <.01; Group 1 vs. Group 2, p <.01; Group 1 vs. Group 3, p =.20). Although 3 of these women in Group 1 consulted their doctor, specific medical treatment was not required. No significant difference was observed in the frequency of maternal report of decreased milk production among the groups, nor was a difference found in infant weight over the first year of life.. These results provide a framework for the management of breastfeeding women receiving St. John's wort.

Topics: Antidepressive Agents; Birth Weight; Breast Feeding; Child Development; Cohort Studies; Depressive Disorder; Female; Gestational Age; Humans; Hypericum; Infant; Lactation; Maternal Exposure; Maternal-Fetal Exchange; Milk, Human; Phytotherapy; Plant Preparations; Pregnancy; Pregnancy Complications

The efficacy of antidepressant medication is generally thought to be well established, whereas that of hypericum (St John's wort) is considered doubtful. The data fail to support these discrepant conclusions. Instead they show that hypericum and conventional antidepressants are equally effective (or ineffective). This suggests that different standards are being used to evaluate the two types of treatment.

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Meta-Analysis as Topic; Phytotherapy; Placebo Effect; Plants, Medicinal; Treatment Outcome

Topics: Depressive Disorder; Drug Therapy, Combination; Humans; Hypericum; Magnoliopsida; Phytotherapy; Plant Extracts; Treatment Outcome

Because the "placebo effect" seems to result from "deception," it is often disparaged and despised. Rethinking this and realizing that these benefits flow largely from the meaning of medical encounters (and are far better understood as "meaning responses"); realizing that there need be no deception to elicit them and that they are often very desirable, engaging fundamental human biological pathways, puts the ethical dilemma in a new light. It seems unethical to avoid--to evade--coming to a full understanding of how meaning can so profoundly improve human well-being.

Topics: Analgesia; Culture; Depressive Disorder; Ethics, Medical; Humans; Hypericum; Physician-Patient Relations; Phytotherapy; Placebo Effect; Semantics; Therapeutics

Extracts of St. John's wort ( Hypericum perforatum ) became increasingly popular as easily available remedies for mild to moderate depression. Comedication with hypericum extract was recently shown to drastically reduce plasma concentration of ciclosporin, digoxin, and indinavir. We investigated the possible interaction of hypericum extract LI160 with amitriptyline. Both antidepressants have a high probability of concomitant use. Twelve patients requiring amitriptyline treatment received a single dose of hypericum extract (900 mg) at day 1, continued by a 12-to 14-day treatment with retarded amitriptyline (75 mg twice daily). Then hypericum (900 mg/day) was added for another 14 to 16 days. Steady-state pharmacokinetics of amitriptyline were compared before and after multiple-dose treatment with hypericum extract. Furthermore, comparisons were made for single-dose kinetics of hypericum-extract ingredients hypericin, pseudohypericin, and hyperforin between the first day of concomitant treatment and LI160 alone. Multiple-dose comedication with LI160 led to a statistically significant decrease in the area under the plasma concentration-time curve within one dosing interval of amitriptyline by 22% ( p = 0.03) and nortriptyline by 41% ( p = 0.002), as well as of all hydroxylated metabolites, except for 10-E-hydroxynortriptyline. Plasma levels of amitriptyline and hydroxylated metabolites gradually decreased, whereas nortriptyline concentrations were already markedly decreased after 3 days of cotreatment with hypericum. Cumulative urinary amounts of amitriptyline and metabolites decreased to the same extent as plasma concentrations upon hypericum comedication. Induction of cytochrome P-450 enzymes or drug transporters (P-glycoprotein) by St. John's wort extract may explain this pharmacokinetic interaction. Physicians should be aware of this interaction when treating patients with amitriptyline.

Topics: Adult; Amitriptyline; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hypericum; Male; Metabolic Clearance Rate; Middle Aged; Nortriptyline; Phytotherapy; Plant Extracts

Topics: Antidepressive Agents; Clinical Trials as Topic; Control Groups; Depressive Disorder; Hypericum; Placebo Effect; Plant Extracts; Sertraline

Topics: Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Humans; Hypericum; Phytotherapy; Plant Extracts; Treatment Outcome

To report 2 cases of adverse reactions to St John's wort, a popular herbal treatment for depression.. We present 2 case histories and review the existing literature regarding St John's wort.. St John's wort may cause serotonin syndrome in sensitive patients. In addition, St John's wort may be associated with hair loss.. For clinical reasons, it is important to recognize and report adverse reactions to herbal remedies and to document that these treatments have side effects commensurate with their potent action on brain neurochemistry.

Topics: Adult; Alopecia; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Hypericum; Male; Phytotherapy; Plants, Medicinal; Schizophrenia; Serotonin Syndrome

Topics: Antidepressive Agents, Tricyclic; Depressive Disorder; Humans; Hypericum; Imipramine; Phytotherapy; Plants, Medicinal; Remission Induction

Topics: Antidepressive Agents, Tricyclic; Depressive Disorder; Humans; Hypericum; Imipramine; Phytotherapy; Plants, Medicinal; Research Design

Topics: Antidepressive Agents, Tricyclic; Depressive Disorder; Humans; Hypericum; Imipramine; Phytotherapy; Plants, Medicinal; Research Design

Topics: Antidepressive Agents, Tricyclic; Depressive Disorder; Humans; Hypericum; Imipramine; Phytotherapy; Plants, Medicinal; Research Design; Sensitivity and Specificity; Statistics as Topic

Topics: Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal

Over-the-counter preparations of St. John's wort are widely used as 'natural' herbal medicine alternative to traditional antidepressants. The antidepressant effect has been shown in numerous placebo controlled studies. The mechanism of action is assumed to be at least in part, similar to conventional antidepressants, due to presynaptic serotonin reuptake inhibition as well as GABA-modulation and inhibition of monoaminoxidases. Because of its favorable safety profile compared to conventional antidepressants, the use of St. John's wort preparations has gained high acceptance with doctors and patients. However, any biologically active compound contains a certain risk of untoward effects and/or interactions which often are neither known nor recognised with the use of herbal remedies. Thus, doctors, pharmacists, and patients might feel themselves in false safety. Recently, a variety of case reports of potentially hazardous interactions due to drug combinations with St. John's wort have been published (e.g. cellular rejection of pancreas-, kidney- as well as heart transplants with ciclosporin therapy, rise of INR with oral anticoagulants, bleeding with oral contraceptives, reduction of plasma concentration of digoxin, indinavir, amitriptyline, and theophylline). We report a case of irregular bleeding with oral contraception and discuss these drug interactions and the mechanisms.

Topics: Adult; Contraceptives, Oral, Combined; Depressive Disorder; Drug Interactions; Female; Herb-Drug Interactions; Humans; Hypericum; Nonprescription Drugs; Plants, Medicinal

Topics: Adult; Depressive Disorder; Humans; Hypericum; Male; Plants, Medicinal; Sexual Dysfunction, Physiological

Topics: Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal; Psychiatric Status Rating Scales

Topics: Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal

Topics: Depressive Disorder; Drug Interactions; Humans; Hypericum; Phytotherapy; Plant Extracts; Plants, Medicinal; Treatment Outcome

Topics: Antioxidants; Ascorbic Acid; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal; Preoperative Care; Research Design; Treatment Failure

Topics: Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypericum; Multicenter Studies as Topic; Phytotherapy; Plant Extracts

Topics: Depressive Disorder; Humans; Hypericum; Plant Extracts; Plants, Medicinal; Treatment Outcome

We describe the case of a patient who developed depression following bilateral orchidectomy for cryptorchidism. He was treated with a conventional selective serotonin reuptake inhibitor antidepressant, but continued to take St John's wort (hypericum) against medical advice. He subsequently developed a manic episode. We discuss postulated modes of action of St John's wort and the possible aetiological importance of testosterone replacement and abnormal gonadotrophin levels in this case.

Topics: Administration, Oral; Adult; Antidepressive Agents; Arousal; Bipolar Disorder; Cryptorchidism; Depressive Disorder; Humans; Hypericum; Male; Orchiectomy; Plants, Medicinal; Postoperative Complications; Sertraline; Testosterone

Topics: Antidepressive Agents; Antidepressive Agents, Tricyclic; Depressive Disorder; Humans; Hypericum; Lymphatic Diseases; Phytotherapy; Plants, Medicinal; Selective Serotonin Reuptake Inhibitors; Thymus Gland

Topics: Adult; Depressive Disorder; Dermatitis, Exfoliative; Drug Eruptions; Humans; Hypericum; Leg Dermatoses; Male; Plants, Medicinal

Topics: Anxiety Disorders; Depressive Disorder; Humans; Hypericum; Plant Extracts; Plants, Medicinal

The annual meeting of the American Psychiatric Association focuses on a variety of topics, including those on psychopharmacology. The latest developments are typically those found in the New Research sections, which is where this summary will focus.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Citalopram; Depressive Disorder; Humans; Hypericum; Olanzapine; Phytotherapy; Pirenzepine; Plants, Medicinal; Psychiatry; Psychotropic Drugs; Societies, Scientific; Testosterone; United States

Topics: Depressive Disorder; Humans; Hypericum; Medicine, Traditional; Phytotherapy; Plant Extracts; Plants, Medicinal

647 patients suffering from mild to moderate depression treated for 6 weeks with hypericum extract LI 160 (Jarsin 300), 1 tablet t.i.d.. The condition of the patients improved in 75% (primary endpoint). The von Zerssen depression score decreased from 19.8-21.2 (95%-CI) at base-line to 8.1-9.3 at week 6 (p < 0.001). All symptoms were improved at week 3 and further at week 6. The condition improved somewhat slower in patients older than 65 years. The severity of the depression did not appear to have an effect on the outcome. Adverse events were reported by 17% of the patients (gastrointestinal 10%). These were mostly mild or moderate. Tolerance was rated in 89% as satisfactory or better.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Depressive Disorder; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plants, Medicinal; Treatment Outcome

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Drug Interactions; Female; Humans; Hypericum; Male; Middle Aged; Plant Extracts; Plants, Medicinal; Treatment Outcome

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Phytotherapy; Plants, Medicinal

Topics: Aged; Chronic Disease; Depressive Disorder; Female; Humans; Hypericum; Male; Middle Aged; Plant Extracts; Plants, Medicinal; Treatment Outcome

Topics: Depression; Depressive Disorder; Humans; Hypericum; Perylene; Phytotherapy; Plant Extracts; Plants, Medicinal; Quercetin; Xanthenes

SJW is a remarkably safe antidepressant with an apparently unique mode of action. Although it has demonstrated efficacy in mild and moderate depression when compared with placebo or tricyclic antidepressants, several research areas beg to be explored. Its effects should be compared with serotonin reuptake inhibitors. Studies in severely depressed patients are lacking, as are studies on its utility as a therapeutic adjunct to standard antidepressants.

Topics: Animals; Anthracenes; Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Nonprescription Drugs; Perylene; Phytotherapy; Plant Extracts; Plants, Medicinal; Protein Kinase C; Quercetin; Rats; Xanthenes

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Perylene; Plants, Medicinal; Quercetin; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Xanthenes

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Humans; Hypericum; Perylene; Plants, Medicinal; Quercetin; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Xanthenes

Topics: Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Humans; Hypericum; Perylene; Plants, Medicinal; Quercetin; Selective Serotonin Reuptake Inhibitors; Xanthenes

A 61-year-old woman with depression developed recurring elevated itching erythematous lesions in light-exposed areas after taking St. John's Wort-extract for three years. Routine patchtesting did not reveal any relevant reactions and photopatch testing was negative. Using a systemic oral photoprovocation test with St. John's Wort, we were able to demonstrate a decrease of the MED-UVB which was reversible after withdrawal of the medication.

Topics: Antidepressive Agents; Depressive Disorder; Dermatitis, Photoallergic; Drug Eruptions; Female; Humans; Hypericum; Middle Aged; Patch Tests; Perylene; Plants, Medicinal; Quercetin; Ultraviolet Rays; Xanthenes

Topics: Antidepressive Agents; Depressive Disorder; Drug Interactions; Humans; Hypericum; Nonprescription Drugs; Perylene; Plants, Medicinal; Quercetin; Treatment Outcome; Xanthenes

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Perylene; Plants, Medicinal; Quercetin; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Xanthenes

Topics: Antidepressive Agents; Depressive Disorder; Humans; Hypericum; Perylene; Plant Extracts; Plants, Medicinal; Quercetin; Xanthenes