hypericum and Depressive-Disorder--Major

Depression is one of the most common mental health disorders and currently affects over 17 million Americans. Up to two-thirds of patients with depression in the United States will seek complementary and alternative or integrative medical treatments and thus medical providers who treat depression should understand that many integrative medical treatments have evidence of efficacy either as monotherapies or as add-on adjuncts to other treatments. This review references guidelines from the Canadian Network for Mood and Anxiety Treatments and Michigan Medicine, along with an updated literature review, to provide a framework for reviewing medications or herbal formulation, as well as other therapies, which have evidence in the treatment of depression. In general, St. John's Wort, Omega-3 Fatty Acids, S-adenosyl-L-methionine, and crocus sativus (saffron) have the highest levels of evidence in the treatment of mild-to-moderate depression. Acetyl-l-carnitine, l-methylfolate, DHEA, and lavender have a moderate level of evidence in treating depression, whereas Vitamin D, one of the most common supplements in the United States, does not have evidence in treating depression. Of the non-medication-based therapies, exercise, light therapy, yoga, acupuncture, and probiotics have evidence in the treatment of depression, whereas a full review of dietary modifications for depression was out of scope for this article.

Topics: Canada; Complementary Therapies; Depressive Disorder, Major; Humans; Hypericum; Integrative Medicine; United States

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

This systematic review evaluated St. John's wort (SJW) for the treatment of Major Depressive Disorder (MDD). The objectives of this review are to (1) evaluate the efficacy and safety of SJW in adults with MDD compared to placebo and active comparator and (2) evaluate whether the effects vary by severity of MDD.. We searched PubMed, CINAHL, PsycINFO, CENTRAL, Embase, AMED, MANTIS, Web of Science, and ICTRP and existing reviews to November 2014. Two independent reviewers screened the citations, abstracted the data, and assessed the risk of bias. We included randomized controlled trials (RCTs) examining the effect of at least a 4-week administration of SJW on depression outcomes against placebo or active comparator in adults with MDD. Risk of bias was assessed using the Cochrane Risk of Bias tool and USPSTF criteria. Quality of evidence (QoE) was assessed using the GRADE approach.. Thirty-five studies examining 6993 patients met inclusion criteria; eight studies evaluated a hypericum extract that combined 0.3 % hypericin and 1-4 % hyperforin. The herb SJW was associated with more treatment responders than placebo (relative risk [RR] 1.53; 95 % confidence interval [CI] 1.19, 1.97; I(2) 79 %; 18 RCTs; N = 2922, moderate QoE; standardized mean differences [SMD] 0.49; CI 0.23, 0.74; 16 RCTs; I(2) 89 %, N = 2888, moderate QoE). Compared to antidepressants, SJW participants were less likely to experience adverse events (OR 0.67; CI 0.56, 0.81; 11 RCTs; moderate QoE) with no difference in treatment effectiveness (RR 1.01; CI 0.90, 1.14; 17 RCTs, I(2) 52 %, moderate QoE; SMD -0.03; CI -0.21, 0.15; 14 RCTs; I(2) 74 %; N = 2248, moderate QoE) in mild and moderate depression.. SJW monotherapy for mild and moderate depression is superior to placebo in improving depression symptoms and not significantly different from antidepressant medication. However, evidence of heterogeneity and a lack of research on severe depression reduce the quality of the evidence. Adverse events reported in RCTs were comparable to placebo and fewer compared with antidepressants. However, assessments were limited due to poor reporting of adverse events and studies were not designed to assess rare events. Consequently, the findings should be interpreted with caution.. PROSPERO CRD42015016406 .

Topics: Antidepressive Agents; Complementary Therapies; Depressive Disorder, Major; Humans; Hypericum; Treatment Outcome

Pharmacological research confirms and supports the clinically observed antidepressant efficacy of St. John's wort (Hypericum perforatum L., SJW). This contribution is an update of a former review by the authors in 2007. Positive evidence of antidepressant effects has been found with SJW preparations, extract fractions, and single constituents. The efficacy of SJW is obviously defined by a range of parallel mechanisms of action, triggered by different constituents. In vitro research showed, among other tests, positive effects in neurotransmitter regulation (in beta adrenergic systems and glutamate receptors) and ion channel conductance. Antidepressant effects were confirmed in typical in vivo models such as the forced swimming test, the open field test, the tail suspension test, or a model of stress-impaired memory. The overall effect cannot be attributed to a single constituent or fraction. SJW is therefore an outstanding example of the total extract being defined as the active constituent of herbal medicines.

Topics: Animals; Antidepressive Agents; Brain; Depressive Disorder, Major; Drug Evaluation, Preclinical; Hypericum; Ion Channels; Neurotransmitter Agents; Phytotherapy; Plant Extracts; Treatment Outcome

Shuganjieyu capsule is a pure herbal pharmaceutical product for depression. Our objective was to explore the effectiveness and safety of Shuganjieyu capsule for the treatment of major depressive disorder in adults.. Eight computerized databases were searched. In addition, randomized controlled trials (RCTs) on Shuganjieyu capsule were hand-searched on seven key Chinese journals. Data were extracted and evaluated by two reviewers independently. Analysis was performed by intention-to-treat where possible. Prespecified subgroup analyses were different-dose regimens, patient spectrum, publication status, and treatment duration.. Seven RCTs with 595 participants were included. Shuganjieyu capsule was superior than placebo in terms of response rate (RR = 2.42, 95% CI: 1.55-3.79; P = 0.0001), remission rate (RR = 4.29, 95% CI: 1.61-11.45; P = 0.004), the scores of the mean change from baseline of the HAM-D17 (MD = -4.17, 95% CI: -5.61 to -2.73; P < 0.00001) and from baseline of traditional Chinese medicine (TCM) syndrome score scale scores (MD = -6.00, 95% CI: -8.25 to -3.75; P < 0.00001). In addition, Shuganjieyu plus venlafaxine had a significantly higher response rate (RR = 1.56, 95% CI: 1.29-1.88; P < 0.00001) and was superior in terms of the scores of the mean change from baseline of the treatment emergent symptoms scale scores (MD = -0.74, 95% CI:-1.12 to -0.35; P = 0.0002) than venlafaxine alone.. Shuganjieyu capsule is superior to placebo in terms of overall treatment effectiveness and safety. Both response rate and remission rate among patients treated with the combination of Shuganjieyu plus venlafaxine were significantly higher than those treated with venlafaxine alone. Due to the considerable risk of bias in majority of trials, recommendations for practice should be cautious, and additional, well-designed RCTs are needed in next step.

Topics: Depressive Disorder, Major; Drug Combinations; Drugs, Chinese Herbal; Eleutherococcus; Humans; Hypericum; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic

The therapeutic value of physical exercise, bright light therapy and dawn simulation, and several pharmacologic treatments, including hypericum (St. John's wort), S-adenosylmethionine, and 5-hydroxytryptophan, are reviewed, with a focus on their use for treating major depressive disorder in children and adolescents and also for alleviating depressed mood in the general (nonclinical) population of youth. For each treatment discussed, all published randomized, double-blind, placebo-controlled trials are summarized, along with some additional selected studies. Nutritional psychopharmacology and several other approaches to treating depression will be presented in an upcoming volume in the Child and Adolescent Psychiatric Clinics of North America.

Topics: 5-Hydroxytryptophan; Adolescent; Antidepressive Agents, Second-Generation; Carbidopa; Child; Complementary Therapies; Depressive Disorder, Major; Enzyme Inhibitors; Exercise Therapy; Humans; Hypericum; Integrative Medicine; Mood Disorders; Phototherapy; Phytotherapy; S-Adenosylmethionine; Treatment Outcome

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Probability; Randomized Controlled Trials as Topic; Research Design; Single-Blind Method; Treatment Outcome

Depression may affect up to 10% of the population, with half of affected people having recurrence of their symptoms. In mild to moderate depression, there is no reliable evidence that any one treatment is superior in improving symptoms of depression, but the strength of evidence supporting different treatments varies. In severe depression, only prescription antidepressants and electroconvulsive therapy are known to improve symptoms.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in mild to moderate and severe depression, and in treatment-resistant depression? Which interventions reduce relapse rates? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 88 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressant drugs (tricyclic antidepressants [including low-dose tricyclic antidepressants], selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or venlafaxine), continuing prescription antidepressant drugs, electroconvulsive therapy, exercise, lithium augmentation, pindolol augmentation, and St John's wort.

Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depression; Depressive Disorder, Major; Double-Blind Method; Gene Library; Humans; Hypericum; United States Food and Drug Administration

To review the clinical evidence supporting complementary and alternative medicine interventions for treating major depressive disorder.. PubMed was searched from January 1966 to February 2010 using the term depressive disorder in combination with St John's wort, S-adenosylmethionine (SAM-e), exercise, acupuncture, omega-3 fatty acids, and folate. Only relevant human trials were selected.. In a large meta-analysis, St John's wort was found to be equivalent to antidepressant drugs with fewer side effects. Exercise reduced depressive scores in 3 meta-analyses. Omega-3 fatty acids reduced depressive scores in a meta-analysis of 16 trials, but publication bias was identified. Oral SAM-e monotherapy reduced depressive scores in 4 of 5 small randomized controlled trials. Folate deficiency is associated with more severe and refractory depression, and supplementation reduced depressive scores in 2 of 3 randomized controlled trials. Acupuncture demonstrated limited efficacy in 1 meta-analysis and 5 other trials.. St John's wort and regular exercise appear effective in the treatment of depression. Acupuncture appears ineffective for depression, but it might offer other health benefits. Other promising therapies include SAM-e, omega-3 fatty acid, and folic acid supplementation in selected patients; further study is warranted.

Topics: Acupuncture Therapy; Complementary Therapies; Depressive Disorder, Major; Dietary Supplements; Exercise Therapy; Fatty Acids, Omega-3; Folic Acid; Humans; Hypericum; Phytotherapy; S-Adenosylmethionine

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

Selective serotonin reuptake inhibitors (SSRIs) like paroxetine have replaced older antidepressants mainly because of a more favorable safety profile, but they are still associated with burdensome side effects. We investigate the tolerability of St. John's wort extract WS 5570, a herbal antidepressant with proven efficacy, in comparison to paroxetine and other SSRIs and placebo. A reanalysis was performed based on the original data from four controlled clinical trials during which 1661 outpatients with major depression (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria) received between 600 and 1800 mg/day WS 5570 (n=1264), 20 or 40 mg/day paroxetine (n=126), or placebo (n=271) for 6 weeks. For single and grouped adverse events, the risk ratios for treatment group comparisons were determined along with their 95% confidence intervals, including comparisons with published data for SSRIs. Across the four trials, the percentage of patients with any adverse events under WS 5570 exposition was comparable with placebo [risk ratio (95% confidence interval): 1.1 (0.9-1.3) in favor of WS 5570] and significantly lower than for paroxetine [2.4 (2.1-2.8)]. Compared with the herbal extract adverse event rates under paroxetine were between 10 and 38-fold higher (point estimates) in five out of seven symptom clusters inspected. WS 5570 was devoid of effects of sedation, anticholinergic reactions, gastrointestinal disturbances, and sexual dysfunction often found during treatment with SSRIs and other synthetic antidepressants. In conclusion, WS 5570 exhibits substantially lower incidence rates of adverse events than paroxetine and other SSRIs.

Topics: Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Paroxetine; Plant Extracts; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

To review selected complementary and alternative medicine (CAM) treatments for major depressive disorder (MDD).. Authors of this report were invited participants in the American Psychiatric Association's Task Force on Complementary and Alternative Medicine.. The group reviewed the literature on individual CAM treatments for MDD, methodological considerations, and future directions for CAM in psychiatry. Individual CAM treatments were reviewed with regard to efficacy in MDD, as well as risks and benefits. Literature searches included MEDLINE and PsycINFO reviews and manual reference searches; electronic searches were limited to English-language publications from 1965 to January 2010 (but manual searches were not restricted by language). Treatments were selected for this review on the basis of (1) published randomized controlled trials in MDD and (2) widespread use with important clinical safety or public health significance relevant to psychiatric practice. An action plan is presented based on needs pertaining to CAM and psychiatry.. Consensus was reached by group conferences. Written iterations were drafted and sent out among group members prior to discussion, resolution of any differences of interpretation of evidence, and final approval.. A review of randomized controlled trials for commonly used CAM treatments such as omega-3 fatty acids, St John's wort (Hypericum), folate, S-adenosyl-L-methionine (SAMe), acupuncture, light therapy, exercise, and mindfulness psychotherapies revealed promising results. More rigorous and larger studies are recommended. Each CAM treatment must be evaluated separately in adequately powered controlled trials. At this time, several CAM treatments appear promising and deserve further study. The greatest risk of pursuing a CAM therapy is the possible delay of other well-established treatments. Clinical, research, and educational initiatives designed to focus on CAM in psychiatry are clearly warranted due to the widespread use of CAM therapies.

Topics: Acupuncture Therapy; Advisory Committees; Complementary Therapies; Depressive Disorder, Major; Fatty Acids, Omega-3; Herbal Medicine; Humans; Hypericum; Meditation; Methionine; Phototherapy; Psychiatry; Randomized Controlled Trials as Topic; Treatment Outcome; United States

Perinatal Major Depressive Disorder (MDD) is common and poses particular treatment dilemmas. Complementary and Alternative Medicine (CAM) treatments are widely used, accessible, and understudied for well-defined psychiatric indications. Women are more likely than men to both suffer from MDD and use CAM.. A PubMed/Medline search was conducted to assess the evidence base for commonly utilized CAM treatments, MDD, and perinatal depression.. Among CAM treatments, omega-3 fatty acids have received the most specific study in terms of epidemiological, preclinical, and clinical research for perinatal depression. Three randomized placebo-controlled trials have been conducted in which investigators assessed omega-3 fatty acids vs. placebo for perinatal depression, with conflicting results. CAM interventions that can be easily added to a treatment plan with little risk and general health benefits for most women include omega-3 fatty acids, exercise, and folate, although data are insufficient at this time to recommend any of these as monotherapy for perinatal depression. S-adenosyl-methionine (SAMe) and bright light therapy may be reasonable to consider based on the evidence in MDD. St. John's Wort requires further study with regard to safety in pregnancy, and drug interactions can be a potential problem.. Further study is required to elucidate the role of CAM treatments for perinatal depression, and the clinical context of perinatal depression requires safe, effective, and accessible treatment options.

Topics: Acupuncture Therapy; Complementary Therapies; Depression, Postpartum; Depressive Disorder, Major; Fatty Acids, Omega-3; Female; Herbal Medicine; Humans; Hypericum; Phototherapy; Phytotherapy; Plant Extracts; Pregnancy; Pregnancy Complications; S-Adenosylmethionine

Hypericum perforatum is a medicinal plant with established antidepressant properties. The aim of this meta-analysis was to compare the efficacy and tolerability of this antidepressant with selective serotonin reuptake inhibitors (SSRIs) as a group of standard antidepressants. For this purpose, Pubmed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies comparing efficacy and/or tolerability of Hypericum with SSRIs in the management of major depressive disorder (MDD). The search terms were: "Hypericum" or "St. John's wort" and "fluoxetine", "paroxetine", "citalopram", "serteraline", "escitalopram", or "fluvoxamine". Data were collected from 1966 to 2008 (up to June). "Clinical response", "remission", "mean reduction in Hamilton Rating Scale for Depression (HAMD) score from baseline", "total adverse events", and "withdrawals due to adverse events" were the key outcomes of interest. Thirteen randomized placebo controlled clinical trials met our criteria and were included. Comparison of SSRIs with placebo yielded a significant relative risk (RR) of 1.22 (95% confidence interval: 1.03-1.45, P=0.02) for clinical response (n=4), a non significant RR of 0.96 (95% CI: 0.71-1.29, P=0.76) for remission (n=4), and a significant effect size [weighted mean difference (wmd+)] of 1.33 (95% CI: 1.15-1.51, P<0.0001) for mean reduction in HAMD score from baseline (n=3). Comparison of Hypericum with SSRIs yielded a non significant relative risk (RR) of 0.99 (95% confidence interval: 0.91-1.08, P=0.83) for clinical response, a non significant RR of 1.1 (95% CI: 0.90-1.35, P=0.35) for remission, and a non-significant wmd+ of 0.32 (95% CI: -1.28-0.64, P=0.52) for mean reduction in HAMD score from baseline, a non significant RR of 0.85 (95% CI: 0.7-1.04, P=0.11) for any adverse events, and a significant RR of 0.53 (95% CI: 0.35-0.82, P=0.004) for withdrawals due to adverse events. Hypericum does not differ from SSRIs according to efficacy and adverse events in MDD. Lower withdrawal from study due to adverse events by Hypericum is an advantage in management of MDD.

Topics: Adult; Aged; Depressive Disorder, Major; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Risk; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

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

The herb St John's wort (Hypericum perforatum) has been used for centuries to treat a variety of medical illnesses. In certain areas of Europe, St John's wort has been a commonly prescribed treatment for depression, but, in the United States, it is available for purchase over the counter as an herbal supplement. Some researchers believe that specific chemical constituents of St John's wort produce change in depression in a way similar to that of antidepressant medications, yet this hypothesis is problematic. In addition, studies that support the efficacy of St John's wort in patients with mild-to-moderate depression have limitations that may affect the accuracy of their conclusions. Studies measuring the effect of St John's wort in major depression have reported conflicting results and need to be reexamined. Because St John's wort is considered by some to be an alternative to conventional therapies, clinicians need to know whether it is an effective and safe treatment for different levels of severity of depression. Current evidence does not support its use, and, because of potential drug interactions, St John's wort is not a benign treatment.

Topics: Depressive Disorder, Major; Drug Interactions; Humans; Hypericum; Plant Extracts; Treatment Outcome

Antidepressants are commonly used drugs with potential for numerous drug interactions. This study aims to systematically review the literature on drug interactions with antidepressants.. We searched MEDLINE (1966 to November 2003) and EMBASE (1980 to 2003), using the heading drug interactions combined with individual antidepressant names. We restricted searches to English-language articles and human studies. We screened drug interaction texts and review articles for relevant studies. We included articles reporting original human data on drug interactions with antidepressants commonly used in North America. Articles were independently evaluated by 2 reviewers on clinical effect, clinical significance, and quality of evidence. Discrepancies were resolved by consensus.. There were 904 eligible interactions, involving 9509 patients, for a total of 598 summary interactions. Of these, 439 (73%) demonstrated an interaction, 148 (25%) had no effect, and 11 (2%) had conflicting evidence. For 510 interactions (85%), the quality of evidence was poor. It was fair for 67 (11%) interactions and good for 10 (2%) interactions. There were no interactions with excellent quality of evidence. There were 145 (24%) interactions of major clinical significance. These were predominantly hypertensive emergencies and serotonin syndrome. Most interacting drugs had central nervous system (CNS) activity. As expected, monoamine oxidase inhibitors (MAOIs) appear to be the most problematic family in terms of potential for serious drug interactions.. Drug interactions with antidepressants are an important cause for concern, but this concern is based primarily on poor evidence. We recommend caution when combining antidepressants with other CNS drugs, particularly when coadministering MAOIs with other substances.

Topics: Cytochrome P-450 Enzyme System; Depressive Disorder, Major; Drug Interactions; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Hypericum; Hypertension; Monoamine Oxidase Inhibitors; Phytotherapy; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome

Hypericum extracts have been regarded as antidepressant drugs without specific side effects by patients, medical professionals and researchers alike. Recently there has been discussion about potential interactions between St. John's wort and other drugs.. To investigate the tolerability of Hypericum extract by comparing adverse event rates observed during clinical trials with the herbal drug to those observed under placebo and synthetic antidepressants.. A data review was performed based on the original data of three double-blind, randomised multicenter trials, during which 594 out-patients suffering from mild to moderate depression according to DSM-IV criteria received 3 x 300 mg/day Hypericum extract (WS 5570, WS 5572, WS 5573) or placebo over a double-blind treatment period of 6 weeks. For the polled data from the three trials, the risk ratios and risk differences versus placebo for single and grouped adverse events were determined along with their 95% confidence intervals. The data were inspected for relevant differences between Hypericum extract and placebo and were compared to trials involving the administration of several synthetic antidepressants.. For the polled data of the three trials, the percentage of patients with any adverse events under Hypericum extract exposition was comparable to placebo. The drug was also found to be devoid of effects of sedation, anticholinergic reactions, gastrointestinal disturbances and sexual dysfunction often found in patients treated with tricyclic antidepressants or selective serotonin reuptake inhibitors.. The analysis did not reveal any specific effects of Hypericum extract.

Topics: Antidepressive Agents; Bridged Bicyclo Compounds; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hypericum; Multicenter Studies as Topic; Phloroglucinol; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Risk; Terpenes

Extracts of St. John's wort have been widely used in the treatment of depression. Our aim was to review information related to the efficacy and safety of St. John's wort as an antidepressant.. Primary and review articles were identified by a search of Medline (1960 to February 2000) and through secondary sources.. All the articles identified from the data sources were evaluated and all relevant information was included in this review. The pharmacokinetics, mechanism of action, efficacy, side effects and drug interactions of St. John's wort have been examined in various studies.. St. John's wort is a promising investigational antidepressant, but the data are not yet sufficient to accept hypericum as a first line antidepressant preparation for treatment of depression. Besides the need for dose standardization and adequate trial lengths, there is a need for studies in severely depressed patients and long-term studies to assess the risk of relapse and recurrence.

Topics: Antidepressive Agents; Depressive Disorder, Major; Drug Interactions; Humans; Hypericum; MEDLINE; Phytotherapy; Plant Extracts; Plants, Medicinal; Safety; Treatment Outcome

A close association between vegetative regulation and affect is common knowledge. Recently, the role of aldosterone and the activity of its receptor [mineralocorticoid receptor (MR)] in the clinical outcome for treatment with standard antidepressants has been shown including low systolic blood pressure and a low concentration of plasma sodium (Na), both of which appear to be related to therapy resistance to standard antidepressants. We carried out a retrospective analysis of a double-blind placebo-controlled trial of St John's wort extract LI160 in 247 outpatients with major depression. The study did not show a difference between the treatment groups; therefore, a pooled dataset of the 6-week completer population of the trial was analyzed. The focus was on the moderating effect of blood pressure and electrolytes on clinical outcome (relative change in Montgomery-Asberg Depression Rating Scale). Low Na/K ratio and high K at screening predicted worse outcome after 6 weeks as measures with the Montgomery-Asberg Depression Rating Scale (P<0.01). Systolic blood pressure at the same time point did not influence the treatment outcome. In conclusion, signs of reduced peripheral MR sensitivity, as reflected by a lower plasma Na/K ratio and/or higher K concentration, predict worse outcome. This is in line with our recent data as well as neuroendocrine findings. The data indicate that widely collected biomarkers, which are related to MR activity, may be useful to identify patients, who are at risk of nonresponse to antidepressant treatment.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Depressive Disorder, Major; Double-Blind Method; Electrolytes; Female; Humans; Hypericum; Male; Middle Aged; Plant Extracts; Potassium; Psychiatric Status Rating Scales; Receptors, Mineralocorticoid; Retrospective Studies; Sodium; Young Adult

efficacy and tolerability of WS(®) 5570 for the treatment of acute mild-to-moderate depression, has been demonstrated in various studies. Here, we present a subgroup analysis of a double blind, randomised trial to compare the therapeutic efficacy of WS(®) 5570 with paroxetine in patients suffering from a major depressive episode with moderate symptom intensity.. moderate depression was defined by a baseline Hamilton Depression Rating Scale (HAM-D) total score between 22 and 25. Patients received, after a single blind placebo run-in phase of 3-7 d, either 3 × 300 mg/d WS(®) 5570 or 20 mg/d paroxetine for six weeks. The change of the HAM-D total score was used to describe the efficacy of WS(®) 5570 compared with paroxetine in the subgroup of patients with moderate depression.. the reductions of the HAM-D total score were significantly more pronounced in patients treated with 3 × 300 mg/d WS(®) 5570 compared to 20 mg/d paroxetine.. patients treated with WS(®) 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine. Keypoints Various studies showed the efficacy and tolerability of WS(®) 5570 for the treatment of acute mild-to-moderate depression. Beneficial effects of WS(®) 5570 have been also shown in patients with moderate-to-severe depression. In this study reductions of the HAM-D total score were significantly more pronounced in patients with moderate depression treated with WS(®) 5570 compared with paroxetine. Patients treated with WS(®) 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine.

Topics: Adolescent; Adult; Aged; Depressive Disorder, Major; Female; Humans; Hypericum; Male; Middle Aged; Outcome Assessment, Health Care; Paroxetine; Plant Extracts; Selective Serotonin Reuptake Inhibitors; Single-Blind Method; Young Adult

We have previously shown an association between patient belief and treatment response in the Hypericum Depression Trial Study Group's 2002 study. We re-examined these data to determine whether clinical improvement was associated with physician belief about assigned therapy.. Three hundred and forty adults with major depression and baseline scores ≥20 on the 17-item Hamilton Depression Scale (HDRS-17) were randomized to Hypericum 900-1500mg/day, sertraline 50-100mg/day, or placebo for 8 weeks. At week 8, physicians guessed their patients' treatment. We analyzed 277 subjects with at least one post-baseline visit and physician guess data. We examined association between guess and improvement in HDRS-17 and whether treatment assignment moderated the effect of belief on remission (final HDRS-17 score <8).. Patient and doctor guesses agreed at 53% for sertraline, 68% for Hypericum, and 52% for placebo (kappa=0.37). Doctors guessed placebo correctly (38%) more than sertraline (18%) or Hypericum (19%) (p=0.001). Adverse event scores were significantly greater among subjects for which the clinicians guessed Hypericum (p<0.001) or sertraline (p=0.005) compared to placebo. Significant improvements in HDRS-17 score were found when comparing the Hypericum-guess (p<0.001) or the sertraline-guess group (p<0.001) against the placebo-guess group. Remission rates were significantly greater for subjects whose clinicians guessed sertraline (p<0.001) or Hypericum (p<0.001) versus placebo.. Doctors tended to guess placebo more easily than Hypericum or sertraline, and their guesses tended to favor active therapies when improvement was more robust. Results show association but not causation, and merit more careful investigation.

Topics: Adult; Attitude of Health Personnel; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Physicians; Plant Extracts; Treatment Outcome

Hypericum perforatum (St John's wort) is used to treat depression, but the effectiveness has not been established. Recent guidelines described the analysis of clinical trials with missing data, inspiring the reanalysis of this trial using proper missing data methods. The objective was to determine whether hypericum was superior to placebo in treating major depression.. A placebo-controlled, randomized clinical trial was conducted for 8 weeks to determine the effectiveness of hypericum or sertraline in reducing depression, measured using the Hamilton depression scale.We performed sensitivity analyses under different assumptions about the missing data process.. Three hundred forty participants were randomized, with 28 % lost to follow-up. The missing data mechanism was not missing completely at random. Under missing at random assumptions, some sensitivity analyses found no difference between either treatment armand placebo, while some sensitivity analyses found a significant difference from baseline to week 8 between sertraline and placebo (-1.28, 95 % credible interval [-2.48; -0.08]), but not between hypericum and placebo (0.56, [-0.64;1.76]). The results were similar when the missing data process was assumed to be missing not at random.. There is no difference between hypericum and placebo, regardless of the assumption about the missing data process. There is a significant difference between sertraline and placebo with some statistical-methods used. It is important to conduct an analysis that takes account of missing data using valid statistically principled methods. The assumptions about the missing data process could influence the results.

Topics: Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypericum; Longitudinal Studies; Male; Models, Statistical; Patient Dropouts; Phytotherapy; Plant Extracts; Psychiatric Status Rating Scales; Sensitivity and Specificity; Sertraline; Treatment Outcome

Hypericum perforatum (St John's wort: SJW) has been extensively studied as an antidepressant in short-term trials, however little research has been conducted on longer-term efficacy.Our objective was to analyze the continuation data from a 26-week randomized, double-blind, controlled study of SJW (LI-160) vs. sertraline and placebo in major depressive disorder. 124 participant "responders" continued treatment after week 8, until week 26. They continued randomly assigned SJW (900-1 500 mg), sertraline (50-100 mg) or matching placebo.At week 26, on the primary outcome, Hamilton depression rating scale (HAM-D) completer scores were: SJW (6.6±4.5), sertraline (7.1±5.4) and placebo (5.7±5.4) with a significant effect for time (p=0.036). Comparisons between all treatments were however non-significant (p=0.61). This effect was mirrored on the other outcomes: the BDI, CGI-severity, CGI-improvement, and on intention-to-treat analyses.While the continuation data revealed an equivocal outcome between treatments at week 26, both SJW and sertraline were still therapeutically effective, with a pronounced "placebo-effect" impeding a significant result at week 26.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Placebos; Plant Extracts; Psychiatric Status Rating Scales; Sertraline

Monoamine oxidase A (MAO-A) inhibitor antidepressants raise levels of multiple monoamines, whereas the selective serotonin reuptake inhibitors (SSRIs) only raise extracellular serotonin. Despite this advantage of MAO-A inhibitors, there is much less frequent development of MAO inhibitors compared with SSRIs. We sought to measure brain MAO-A occupancy after 6 weeks of treatment in depressed patients with a clinically effective dose of a selective MAO-A inhibitor and measure MAO-A occupancy after repeated administration of St. John's wort, an herb purported to have MAO-A inhibitor properties.. Participants underwent 2 [(11)C]-harmine positron emission tomography scans. Healthy controls completed a test-retest condition, and depressed patients were scanned before and after repeated administration of moclobemide or St. John's wort for 6 weeks at the assigned dose. We measured MAO-A VT, an index of MAO-A density, in the prefrontal, anterior cingulate and anterior temporal cortices, putamen, thalamus, midbrain and hippocampus.. We included 23 participants (10 controls and 13 patients with major depressive disorder [MDD]) in our study. Monoamine oxidase A VT decreased significantly throughout all regions after moclobemide treatment in patients with MDD compared with controls (repeated-measures analysis of variance, F1,15 = 71.08-130.06, p < 0.001 for all regions, mean occupancy 74% [standard deviation 6%]). Treatment with St. John's wort did not significantly alter MAO-A VT.. The occupancy estimates are limited by the sample size of each treatment group; hence, our estimate for the overall moclobemide occupancy of 74% has a 95% confidence interval of 70%-78%, and we can estimate with 95% certainty that the occupancy of St. John's wort is less than 5%.. For new MAO-A inhibitors, about 74% occupancy at steady-state dosing is desirable. Consistent with this, St. John's wort should not be classified as an MAO-A inhibitor. The magnitude of MAO-A blockade during moclobemide treatment exceeds the elevation of MAO-A binding during illness by at least 30%, suggesting that the treatment effect should exceed the disease effect when designing selective antidepressants for this target.

Topics: Adult; Brain; Carbon Radioisotopes; Depressive Disorder, Major; Female; Harmine; Humans; Hypericum; Male; Middle Aged; Moclobemide; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Phytotherapy; Plant Preparations; Positron-Emission Tomography; Radioligand Assay

To reanalyze data from a 2002 study by the Hypericum Depression Trial Study Group to determine whether patients who believed they were receiving active therapy rather than placebo obtained greater improvement, independent of treatment.. Three hundred forty adults with major depressive disorder (according to the Structured Clinical Interview for DSM-IV) and baseline scores of ≥ 20 on the 17-item Hamilton Depression Rating Scale (HDRS-17) were randomized to Hypericum perforatum 900-1,500 mg/d, sertraline 50-100 mg/d, or placebo and were asked to guess their assigned treatment after 8 weeks. This reanalysis of data was performed from October 1, 2009, to April 15, 2011. The intent-to-treat sample included 207 subjects (mean age = 44 years) who had (1) at least 1 postbaseline visit; (2) adherence data based on serum levels of hyperforin, sertraline, and desmethylsertraline; and (3) guess data. Univariate factorial analysis of variance was used to determine whether treatment assignment affected clinical improvement according to HDRS-17 score and whether this effect was moderated by patient guess of sertraline, Hypericum, or placebo. Analysis of covariance was used to determine whether side effects mediated improvement in the context of patient guess and assigned treatment. χ₂ analyses compared response rates (≥ 50% decrease in HDRS-17 score) between the guess groups and between the treatment groups within each guess group.. Assigned treatment had no significant effect on clinical improvement (P = .65), but patient guess was significantly associated with improvement (P < .001), and treatment and guess interacted significantly (P = .005). Among subjects who guessed placebo, clinical improvement was small and did not differ significantly across treatments. Among subjects who guessed Hypericum, improvement was large and did not differ significantly across treatments. Among subjects who guessed sertraline, those who received placebo or sertraline had large improvements, but those who received Hypericum had significantly less improvement (P < .001). Similar findings were obtained for response rates.. Patient beliefs regarding treatment may have a stronger association with clinical outcome than the actual medication received, and the strength of this association may depend upon the particular combination of treatment guessed and treatment received.

Topics: Adult; Analysis of Variance; Depressive Disorder, Major; Humans; Hypericum; Middle Aged; Patients; Placebos; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Antidepressants increase melatonin levels, but it is still unclear whether this effect is related to the improvement of depressive symptoms or to unrelated pharmacological action of antidepressants. To answer this question, the effect of antidepressants on 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, was examined in drug-free depressed patients - most of them antidepressant-naive. aMT6s was evaluated in 34 depressed patients, before and after 8 weeks of placebo (n = 12) or antidepressant (n = 22; fluoxetine, duloxetine or Hypericum perforatum). Both groups showed an improvement of depressive symptoms after treatment compared to baseline (Hamilton Depression scores): 17.0 +/- 1.4 vs. 9.0 +/- 2.8, P = 0.007 for placebo, and 18.6 +/- 1.1 vs. 11.8 +/- 1.6, P < 0.001 for antidepressants). After treatment, aMT6s levels increased after antidepressants (P < 0.01), but not after placebo (P > 0.05). As depressive symptoms improved both in patients taking antidepressant and in those taking placebo, but an effect of antidepressants could only be seen in those taking antidepressants, we suggest that melatonin changes after antidepressants are more likely due to a pharmacological action of these drugs on melatonin secretion.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Duloxetine Hydrochloride; Female; Fluoxetine; Humans; Hypericum; Male; Melatonin; Middle Aged; Plant Extracts; Severity of Illness Index; Thiophenes; Treatment Outcome

We report the first randomised controlled trial (RCT) using a combination of St. John's wort (SJW) and Kava for the treatment of major depressive disorder (MDD) with comorbid anxiety.. Twenty-eight adults with MDD and co-occurring anxiety were recruited for a double-blind RCT. After a placebo run-in of 2 weeks, the trial had a crossover design testing SJW and Kava against placebo over two controlled phases, each of 4 weeks. The primary analyses used intention-to-treat and completer analyses.. On both intention-to-treat (p = 0.047) and completer analyses (p = 0.003), SJW and Kava gave a significantly greater reduction in self-reported depression on the Beck Depression Inventory (BDI-II) over placebo in the first controlled phase. However, in the crossover phase, a replication of those effects in the delayed medication group did not occur. Nor were there significant effects on anxiety or quality of life.. There was some evidence of antidepressant effects using SJW and Kava in a small sample with comorbid anxiety. Possible explanations for the absence of anxiolysis may include a potential interaction with SJW, the presence of depression, or an inadequate dose of Kava.

Topics: Adolescent; Adult; Antidepressive Agents; Anxiety Disorders; Cross-Over Studies; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hypericum; Kava; Male; Middle Aged; Pilot Projects; Plant Extracts; Psychometrics; Quality of Life; Young Adult

The efficacy and safety of Hypericum extract WS 5570 in preventing relapse during 6 months' continuation treatment and 12 months' long-term maintenance treatment after recovery from an episode of recurrent depression were investigated in a double-blind, placebo controlled multicenter trial. Adult out-patients with a recurrent episode of moderate major depression, a 17-item Hamilton Depression Rating Scale (HAMD) total score > or =20 and > or =3 previous episodes in 5 years participated. After 6 weeks of single-blind treatment with 3 x 300 mg/day WS 5570 patients with score < or =2 on item 'Improvement' of the Clinical Global Impressions (CGI) scale and a HAMD total score decrease > or =50% versus baseline were randomized to 3 x 300 mg/day WS 5570 or placebo for 26 weeks. 426 patients were evaluated for efficacy. Relapse rates during continuation treatment were 51/282 (18.1%) for WS 5570 and 37/144 (25.7%) for placebo. Average time to relapse was 177+/-2.8 and 163+/-4.4 days for WS 5570 and placebo, respectively (time-to-event analysis; p=0.034; alpha=0.025 one-sided). Patients treated with WS 5570 showed more favorable HAMD and Beck Depression Inventory time courses and greater over-all improvement (CGI) than those randomized to placebo. In long-term maintenance treatment a pronounced prophylactic effect of WS 5570 was observed in patients with an early onset of depression as well as in those with a high degree of chronicity. Adverse event rates under WS 5570 were comparable to placebo. WS 5570 showed a beneficial effect in preventing relapse after recovery from acute depression. Tolerability in continuation and long-term maintenance treatment was on the placebo level.

Topics: Acute Disease; Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Outpatients; Phytotherapy; Plant Extracts; Psychiatric Status Rating Scales; Sample Size; Secondary Prevention; Sertraline; Treatment Outcome; Young Adult

Using the data of a positive d.b.c.t. comparing an hypericum extract (W55570) to placebo in depressed patients we explored whether the Ham D(6) was unidimentional and in case of a positive answer whether the total score was as sensitive as the total score of the Ham D(17).. The study was a 6 weeks double blind placebo controlled trial comparing 300 mg of hypericum t.i.d (n=186), to placebo (n=189), in patients with a single or recurrent depression according to DSM-IV. Superiority of hypericum versus placebo on the main outcome criterion (HDRS 17) was already published. The unidimensionality of the Hamilton depression scale 6 and 17 items were tested using a Mokken scale analysis. The effect size according to the initial severity of depression was calculated on the ITT last observation carried forward population.. The Ham D(6), covering the core symptoms of depression was unidimensional, implying that improving this score reflects a true antidepressant effect. The Ham D(17) was not unidimensional. Hypericum was an effective antidepressant in patients with a pre-treatment score of 12 or more (n=208) on the Ham D(6), the effect size was 0.46. No difference with placebo was observed for those with a score of less than 12 (n=167).. For the evaluation of an antidepressant effect, because of its specificity and sensitivity, the Ham D(6) should be used as a primary outcome measure rather than the Ham D(17).

Topics: Adolescent; Adult; Aged; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Humans; Hypericum; Middle Aged; Phytotherapy; Sensitivity and Specificity; Severity of Illness Index; Surveys and Questionnaires

Our objective was to assess for the relationship between timing of clinical improvement and resolution of depressive symptoms during the treatment of major depressive disorder (MDD). Thirty-nine MDD outpatients who responded following a 12-week, double-blind study comparing Hypericum perforatum, fluoxetine or placebo were included in the analysis.. Onset of clinical improvement was defined as a 25% decrease in 17-item Hamilton Depression Scale (HDRS-17) scores that was not followed by a subsequent worsening of symptoms. Controlling for baseline symptom severity, we then assessed for the relationship between timing of clinical improvement and depressive symptom severity at endpoint.. Among responders, earlier clinical improvement predicted lower HDRS-17 scores at week 12 (p = 0013). This was also true of responders who received active treatment (n = 29, p = 0.0113) but not placebo responders (n = 10; p > 0.05). Finally, patients with an early onset of clinical improvement (occurring during the first 2 weeks) had lower week 12 HDRS-17 scores than patients with a late onset of clinical improvement (p = 0.0404).. In the present work, earlier as well as early clinical improvement during treatment is predictive of greater symptom resolution at endpoint among responders. This was replicated among patients who received active treatment (either hypericum or fluoxetine) but not placebo.

Topics: Adult; Depressive Disorder, Major; Double-Blind Method; Female; Fluoxetine; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Preparations; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome

The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen's Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo.. Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs.. From almost identical baseline values of 21.9 +/- 1.2 points (hypericum extract), 21.8 +/- 1.2 points (citalopram) and 22.0 +/- 1.2 points (placebo), the HAMD score was reduced to 10.3 +/- 6.4 (hypericum extract), 10.3 +/- 6.4 (citalopram) and 13.0 +/- 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with "certain", "probable" or "possible" relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as "good" or "very good".. The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.

Topics: Adult; Citalopram; Combined Modality Therapy; Depressive Disorder, Major; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypericum; Male; Phytotherapy; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index

Hypericum extract (HE) might be favourably active in depressed patients with reversed vegetative signs (RVS). Therefore, we performed an exploratory subgroup analysis of a three-armed study to compare HE, fluoxetine, and placebo in patients with major depressive disorder (MDD) in a 12 wk trial. A total of 135 patients were randomized to 12 wk treatment with HE LI 160 (900 mg/d), fluoxetine (20 mg/d), or placebo. Patients with RVS were defined in two steps, according to DSM-IV. First, patients with melancholy-related vegetative signs were excluded. Secondly, patients had to have at least one score of 2 for the items 22-26 of the HAMD-28 scale, which are related to hypersomnia and hyperphagia. Twenty-seven patients remained in the group. Analysis of covariance (ANCOVA) was applied using the HAMD-17 score. Secondly a chi2 test for response was performed, using the same and further an adapted criterium as in recently published studies. ANCOVA revealed a trend to a global difference. Post-hoc analysis showed a trend to superiority of HE compared to placebo and to fluoxetine, but a very large effect size for both differences. Fluoxetine was not different from placebo. The adapted response criterium showed a significant global difference as well as a significant superiority of HE over placebo and over fluoxetine. These data are based on a small sample size and must be considered tentative. A characterization of vegetative features of patients with depression could lead to an overall increased effect size in the treatment with HE.

Topics: Analysis of Variance; Depressive Disorder, Major; Double-Blind Method; Fluoxetine; Humans; Hypericum; Phytotherapy; Placebos; Plant Extracts; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome

The 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety/Somatization factor includes six items: Anxiety (psychic), Anxiety (somatic), Somatic Symptoms (gastrointestinal), Somatic Symptoms (general), Hypochondriasis and Insight. This study examines the relationship between early changes (defined as those observed between baseline and week 1) in these HAMD-17 Anxiety/Somatization Factor items and treatment outcome among major depressive disorder (MDD) patients who participated in a study comparing the antidepressant efficacy of a standardized extract of hypericum with both placebo and fluoxetine. Following a 1-week, single-blind washout, patients with MDD diagnosed by the Structured Clinical Interview for DSM-IV (SCID) were randomized to 12 weeks of double-blind treatment with hypericum extract (900 mg/day), fluoxetine (20 mg/day) or placebo. The relationship between early changes in HAMD-17 anxiety/somatization factor items and treatment outcome was assessed separately for patients who received study treatment (hypericum or fluoxetine) versus placebo with a logistic regression method. One hundred and thirty-five patients (female 57%, mean age=37.3+/-11.0 years; mean baseline HAMD-17=19.7+/-3.2 years) were randomized to double-blind treatment and were included in the intent-to-treat (ITT) analyses. After adjusting for baseline HAMD-17 scores and for multiple comparisons with the Bonferroni correction, patients who remitted (HAMD-17 score <8) after study treatment had significantly greater early improvement in Somatic Symptoms (General) scores than non-remitters. No other significant differences in early changes were noted for the remaining items between remitters versus non-remitters who received active treatment. For patients treated with placebo, early change was not predictive of remission for any of the items after Bonferroni correction. In conclusion, the presence of early improvement on the HAMD-17 item concerning fatigue and general somatic symptoms is significantly predictive of achieving remission at endpoint with active study treatment but not with placebo.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antidepressive Agents, Second-Generation; Anxiety; Depressive Disorder, Major; Double-Blind Method; Female; Fluoxetine; Humans; Hypericum; Male; Middle Aged; Plant Extracts; Psychiatric Status Rating Scales; Somatoform Disorders; Treatment Outcome

A previously reported clinical trial of Hypericum perforatum (St John's wort) in depression did not demonstrate efficacy. We assessed treatment adherence by measuring plasma hyperforin and evaluated the possible impact of adherence on study results.. Outpatients with major depression (N = 340) were randomized to an 8-week trial of H. perforatum (900-1500 mg/d), sertraline (50-100 mg/d) as active comparator, or placebo. Plasma was available from 292 patients (86% of randomized). Samples from the placebo and H. perforatum groups were assayed for hyperforin, and samples from the sertraline group for sertraline/N-desmethyl-sertraline.. Of the 104 patients randomized to placebo, 18 (17%) had detectable plasma hyperforin. Of the 97 patients randomized to H. perforatum, 17 (17%) had no detectable plasma hyperforin. All the assayed sertraline patients (N = 91) had plasma sertraline/N-desmethyl-sertraline. The clinical trial conclusions remained unchanged when only patients with plasma assay consistent with random assignment were included in the analyses.. One of every 6 patients assigned to placebo had plasma hyperforin, and 1 of every 6 patients assigned to H. perforatum had no detectable plasma hyperforin. The finding underscores the difficulty of enforcing treatment adherence in clinical trials of preparations that are readily available in the community.

Topics: Adult; Biomarkers; Bridged Bicyclo Compounds; Chi-Square Distribution; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; National Institutes of Health (U.S.); Patient Compliance; Phloroglucinol; Statistics, Nonparametric; Terpenes; United States

This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine.. After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate.. One hundred thirty-five patients (57% women; mean age, 37.3 +/- 11.0; mean HAMD-17, 19.7 +/- 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean +/- SD, 10.2 +/- 6.6) compared with the fluoxetine group (n = 47; 13.3 +/- 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 +/- 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated.. St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Double-Blind Method; Endpoint Determination; Female; Fluoxetine; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Psychiatric Status Rating Scales

Recent research with several synthetic antidepressants indicates that early improvement during the initial weeks of treatment may be a highly sensitive predictor of therapeutic success in major depression. We investigated whether early improvement is sensitive and specific in predicting sustained response and non-response to antidepressant treatment with Hypericum extract WS(R) 5570/5572 and whether the results reported for synthetic antidepressants apply to these Hypericum extracts as well.. We analyzed original data of 3 double-blind, randomized trials including a total of 594 adult out-patients suffering from major depression according to DSM-IV criteria, who received well-characterized Hypericum extract preparations WS(R) 5570, WS(R) 5572, WS(R) 5573 or placebo for 6 weeks. The main outcome measure was the prediction of a sustained > or = 50 % decrease of the Hamilton Depression Scale (HAM-D) total score versus baseline ('sustained response') by the presence of > or =20 % HAM-D total score improvement after 1 and 2 weeks of treatment ('early improvement').. For Hypericum extract, early improvement had a sensitivity of 87 % (95 % confidence interval [CI], 82-93 %) and a specificity of 54 % (95 % CI, 45-62 %) at day 14, and a sensitivity of 43 % (95 % CI, 35-51 %) and a specificity of 86 % (95 % CI, 80-92 %) at day 7 for predicting sustained response. After 2 weeks of treatment, 78 % (95 % CI, 69-87 %) of the patients who failed to improve did not show sustained response later during treatment.. A substantial fraction of the patients treated with Hypericum extracts WS(R) 5570/5572 showed a meaningful reduction of depressive symptoms during the first two weeks of treatment (early improvement), which was found to be a sensitive predictor of sustained response. The results determined for the herbal extracts were comparable to those for effective synthetic antidepressants investigated previously.

Topics: Adult; Confidence Intervals; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Mental Status Schedule; Middle Aged; Plant Extracts; Predictive Value of Tests; Sensitivity and Specificity; Time Factors; Treatment Outcome

This pilot study examined the effectiveness, safety, tolerability, and pharmacodynamics of Hypericum perforatum (St. John's wort) in the treatment of youths diagnosed with major depressive disorder.. Youths 6 to 16 years of age meeting DSM-IV criteria for major depressive disorder with depressive symptoms of at least moderate severity were eligible to enroll between January 1999 and January 2001 in this 8-week, prospective, open-label, outpatient study. Outcome measures included the Children's Depression Rating Scale-Revised (CDRS-R) and the Clinical Global Impressions (CGI) scale. A priori criteria for response consisted of a CDRS-R score of

Topics: Adolescent; Child; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Tolerance; Female; Humans; Hypericum; Male; Outcome Assessment, Health Care; Phytotherapy; Pilot Projects; Prospective Studies; Severity of Illness Index; Surveys and Questionnaires

Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated.. To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder.. Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States.. Adult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20.. Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks.. Change in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores.. On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was -9.20 (0.67) (95% confidence interval [CI], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% CI, -10.01 to -7.35) for H perforatum (P =.59) and -10.53 (0.72) (95% CI, -11.94 to -9.12) for sertraline (P =.18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum-treated patients (P =.21) and 24.8% of sertraline-treated patients (P =.26). Sertraline was better than placebo on the CGI improvement scale (P =.02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo.. This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Psychiatric Status Rating Scales; Regression Analysis; Sertraline; Statistics, Nonparametric

Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation.. To compare the efficacy and safety of a standardized extract of St John's wort with placebo in outpatients with major depression.. Randomized, double-blind, placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States.. Two hundred adult outpatients (mean age, 42.4 years; 67.0% female; 85.9% white) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20.. Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n = 102) for 8 weeks.. The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I).. The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction (for HAM-D scores, P<.001, P =.16, and P =.58, respectively). Analysis of covariance showed nonsignificant effects for BDI and GAF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P =.02), but the rates were very low in the full intention-to-treat analysis (14/98 [14.3%] vs 5/102 [4.9%], respectively). St John's wort was safe and well tolerated. Headache was the only adverse event that occurred with greater frequency with St John's wort than placebo (39/95 [41%] vs 25/100 [25%], respectively).. In this study, St John's wort was not effective for treatment of major depression.

Topics: Adult; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Hypericum; Male; Middle Aged; Phytotherapy; Plant Extracts; Plants, Medicinal; Psychiatric Status Rating Scales; Regression Analysis

St John's wort (Hypericum perforatum) has been known for centuries for its therapeutic properties and its efficacy as an antidepressant has been confirmed by a growing body of evidence. During the last two decades it has also come to prominence with a wider public, due to advertising efforts across Europe and United States of America. However, its availability without prescription, as an over-the-counter medication, raises some concern regarding its clinical management and unsupervised administration to individuals with psychopathological risks. To date, the evidence available regarding the administration of Hypericum in people with severe mental health problems is still meager and refers mainly to affective disorder spectrum or psychotic relapse in people with established diagnoses. To the best of our knowledge, this is the first report regarding the onset of psychotic features in a patient presenting with psychotic diathesis.. The case discussed in this report is a 25-year-old white man, not known to the psychiatric services, with a history of brief and self-remitting drug-induced psychosis and a positive family history of psychotic depression. He was admitted to hospital due to the onset of florid psychotic symptoms concomitant with self-administration of Hypericum perforatum.. The aim of this report is to promote further systematic research, draw the attention of clinicians to the potential risks of Hypericum precipitating psychosis, and raise awareness among health professionals to investigate and caution their patients on the haphazard use of phytotherapeutics such as Hypericum.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Helicobacter Infections; Humans; Hypericum; Male; Phytotherapy; Psychoses, Substance-Induced; Self Medication; Substance-Related Disorders

Celery root belongs to a group of plants classified as the umbelliferous family, which contains phytoestrogens. Phytoestrogens are structurally similar to estrogen as they share a pair of hydroxyl groups and phenolic ring, which enables them to bind to estrogen receptors directly, making them a herbal remedy for low estrogen states such as menopause. We present a case of a female patient with depression who was stabilized on venlafaxine and St John's Wort, and who developed a manic episode due to elevated serum venlafaxine levels after she started taking celery extracts for menopausal related issues. We proffer a hypothesis for this unusual occurrence.

Topics: Antidepressive Agents, Second-Generation; Apium; Bipolar Disorder; Depressive Disorder, Major; Female; Herb-Drug Interactions; Humans; Hypericum; Menopause; Middle Aged; Phytotherapy; Plant Preparations; Plant Roots; Psychiatric Status Rating Scales; Treatment Outcome; Venlafaxine Hydrochloride; Withholding Treatment

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

Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression, whether BDNF levels are related to the clinical features of depression and whether distinct antidepressants affect BDNF levels equally. We addressed these questions and investigated serum BDNF levels in 962 depressed patients, 700 fully remitted persons (≥6 months) and 382 healthy controls. We found serum BDNF levels to be low in antidepressant-free depressed patients relative to controls (P=0.007) and to depressed patients who were treated with an antidepressant (P=0.001). BDNF levels of fully remitted persons (whether unmedicated or treated with an antidepressant) were comparable to those of controls. Analyzing the sample of antidepressant-free depressed patients showed that BDNF levels were unrelated to the core clinical features of depression such as its severity or first versus a recurrent episode. The antidepressant associated upregulation of serum BDNF in depressed patients was confined to selective serotonin reuptake inhibitors (SSRIs) (P=0.003) and St John's wort (P=0.03). Our results suggest that low serum levels of BDNF are a state abnormality that is evident during depression and normalizes during remission. Increases in serum levels of BDNF during antidepressant treatment appear to be confined to some antidepressants and do not parallel clinical characteristics, such as the severity of depressive symptoms.

Topics: Adult; Antidepressive Agents, Tricyclic; Anxiety Disorders; Biomarkers; Brain-Derived Neurotrophic Factor; Convalescence; Depressive Disorder, Major; Drug Monitoring; Female; Humans; Hypericum; Male; Middle Aged; Models, Neurological; Models, Psychological; Phytotherapy; Plant Extracts; Recurrence; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index

To assess whether early changes in Hamilton Depression Rating Scale-17 anxiety/somatization items predict remission in two controlled studies of Hypericum perforatum (St John's wort) versus selective serotonin reuptake inhibitors for major depressive disorder. The Hypericum Depression Trial Study Group (National Institute of Mental Health) randomized 340 patients to Hypericum, sertraline, or placebo for 8 weeks, whereas the Massachusetts General Hospital study randomized 135 patients to Hypericum, fluoxetine, or placebo for 12 weeks. The investigators examined whether remission was associated with early changes in anxiety/somatization symptoms. In the National Institute of Mental Health study, significant associations were observed between remission and early improvement in the anxiety (psychic) item (sertraline arm), somatic (gastrointestinal item; Hypericum arm), and somatic (general) symptoms (placebo arm). None of the three treatment arms of the Massachusetts General Hospital study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety (psychic; selective serotonin reuptake inhibitors arm), somatic (gastrointestinal), and hypochondriasis (Hypericum arm), and anxiety (psychic) and somatic (general) symptoms (placebo arm). In the entire sample, remission was associated with the improvement in the anxiety (psychic), somatic (gastrointestinal), and somatic (general) items. The number and the type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the Hamilton Depression Rating Scale-17 anxiety/somatization items may help to predict remission of major depressive disorder.

Topics: Depressive Disorder, Major; Fluoxetine; Humans; Hypericum; Logistic Models; Outpatients; Phytotherapy; Plant Preparations; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Remission Induction; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity - important risk factors in suicide. We hypothesized that patients with major depressive disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers.. Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers (n=31) and patients with MDD with (n=14) and without (n=16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels.. KYN levels differed across groups (F=4.03, df=(2,58), and p=0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters (t=2.105, df=58, and p=0.040), who did not differ from healthy volunteers (t=0.418, df=58, and p=0.677). In post hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters.. These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Cytokines; Depressive Disorder, Major; Duloxetine Hydrochloride; Female; Humans; Hypericum; Impulsive Behavior; Inflammation; Kynurenine; Male; Middle Aged; Neopterin; Phytotherapy; Recurrence; Serotonin; Smoking; Suicide, Attempted; Thiophenes; Tryptophan; Young Adult

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Citalopram; Depressive Disorder, Major; Female; Germany; Humans; Hypericum; Male; Medication Adherence; Middle Aged; Multicenter Studies as Topic; Phytotherapy; Plant Extracts; Prospective Studies; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Young Adult

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

It is essential for the integrity of double-blind clinical trials that during the study course the individual treatment allocations of the patients as well as the treatment effect remain unknown to any involved person. Recently, methods have been proposed for which it was claimed that they would allow reliable estimation of the treatment effect based on blinded data by using information about the block length of the randomization procedure. If this would hold true, it would be difficult to preserve blindness without taking further measures. The suggested procedures apply to continuous data. We investigate the properties of these methods thoroughly by repeated simulations per scenario. Furthermore, a method for blinded treatment effect estimation in case of binary data is proposed, and blinded tests for treatment group differences are developed both for continuous and binary data. We report results of comprehensive simulation studies that investigate the features of these procedures. It is shown that for sample sizes and treatment effects which are typical in clinical trials, no reliable inference can be made on the treatment group difference which is due to the bias and imprecision of the blinded estimates.

Topics: Bias; Biometry; Data Interpretation, Statistical; Depressive Disorder, Major; Double-Blind Method; Humans; Hypericum; Likelihood Functions; Models, Statistical; Phytotherapy; Random Allocation; Randomized Controlled Trials as Topic; Treatment Outcome

In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is widespread interest in complementary and alternative medicine (CAM) therapies in the treatment of major depressive disorder (MDD).. The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support. This section on "Complementary and Alternative Medicine Treatments" is one of 5 guideline articles.. There is Level 1 evidence to support light therapy in seasonal MDD and St. John's wort in mild to moderate MDD. There is also some evidence for the use of exercise, yoga and sleep deprivation, as well as for omega-3 fatty acids and SAM-e . Support for other natural health products and therapies is still limited.. The evidence base remains limited and studies often have methodological problems, including small samples, variability in dose, short duration of treatment, unknown quality of the agent and limited long-term data. Safety data are also sparse with little information about drug interactions.. Some CAM treatments have evidence of benefit in MDD. However, problems with standardization and safety concerns may limit their applicability in clinical practice.

Topics: Acupuncture Therapy; Adult; Antidepressive Agents; Complementary Therapies; Dehydroepiandrosterone; Depressive Disorder, Major; Dietary Supplements; Exercise Therapy; Fatty Acids, Omega-3; Herbal Medicine; Humans; Hypericum; Phototherapy; Phytotherapy; S-Adenosylmethionine; Sleep Deprivation; Tryptophan; Yoga

Clinical experience suggests the use of alternative remedies, such as St. John's Wort (SJW), in adolescents with affective disorders is increasing. In view of the paucity of documented, well-established, and safe antidepressant medications for children and adolescents, it was important to investigate the potential usefulness of SJW in adolescents with major depressive disorders (MDD).. An 8-week, open-label study evaluated the potential efficacy and safety of SJW (300 mg TID) in adolescents with MDD. Twenty-six patients, 12-17 years of age (mean age, 14.8 years) were enrolled in the study. Of the 11 patients who completed the study, 9 patients (82%) showed significant clinical improvement based on Clinical Global Improvement (CGI) change scores (treatment response was indicated by a clinical improvement rating of either very much improved or much improved at the final visit). Of the 15 patients (58%) who did not complete the study, 8 patients were noncompliant and 7 patients were discontinued because of persisting or worsening depression. Of the 8 noncompliant patients, at week 8, 2 patients (25%) remained unchanged, 1 patient (12.5%) was minimally improved, 4 patients (75%) were much improved, and 1 patient (12.5%) was very much improved, based on the CGI change score.. Preliminary findings suggest that SJW is well tolerated and may be clinically effective in the treatment of some adolescents with mild depression. Controlled trials of SJW in adolescents with MDD are suggested.

Topics: Adolescent; Analysis of Variance; Child; Depressive Disorder, Major; Female; Humans; Hypericum; Male; Pilot Projects; Psychiatric Status Rating Scales

Little is known about the beliefs of patients suffering from major depression as to the causes of their illness and effective treatments. This study introduces a new instrument for capturing these beliefs, the Explanatory Model for Depression (EMD) Questionnaire, and explores the beliefs of patients participating in a clinical trial of an alternative medicine, Hypericum perforatum. Although the EMD was originally conceptualized as having five factors pertaining to models of the illness and treatment approaches, the data suggest that patient beliefs are aligned on two factors pertaining to internal and external locus of control. Strong beliefs on either of the EMD locus of control subscales are associated with more severe depression. More importantly, strong beliefs on the external locus of control subscale are associated with less improvement over the 8-week period of observation. These results support the role of patients' beliefs in their recovery from depression and suggest that patients who believe the causes of their depression are outside of their control are less likely to improve over time. It is important to note that beliefs did not mediate the effect of treatment on depression in this study, perhaps because patients were blinded to their treatment condition. Future studies should explore whether patient beliefs have an even greater impact when patients are aware of the treatment they are receiving and can determine whether that treatment is consistent with their beliefs.

Topics: Adult; Culture; Depressive Disorder, Major; Female; Humans; Hypericum; Internal-External Control; Male; Phytotherapy; Plant Extracts; Psychometrics; Randomized Controlled Trials as Topic; Severity of Illness Index; Surveys and Questionnaires

Topics: Depressive Disorder, Major; Humans; Hypericum; Mental Health Services; Phytotherapy; Psychiatric Status Rating Scales; Psychiatry

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

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

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

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

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

Topics: Adult; Depressive Disorder, Major; Female; Humans; Hypericum; Male; Multicenter Studies as Topic; Phytotherapy; Plants, Medicinal; Randomized Controlled Trials as Topic

Topics: Adult; Depressive Disorder, Major; Female; Humans; Hypericum; Male; Phytotherapy; Plant Extracts; Plants, Medicinal; Randomized Controlled Trials as Topic; Treatment Outcome