Hyperforin content determines the magnitude of the St John's Wort–cyclosporine drug interaction Effect of St John's wort on the pharmacokinetics of fexofenadine The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication. Effectiveness of St John's wort in major depression: a randomized controlled trial. Effects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. St. John's wort has no effect on pain in polyneuropathy The interaction between St John's wort and an oral contraceptive St John's wort versus placebo in obsessive–compulsive disorder: results from a double-blind study Evaluating the safety of St. John's Wort in human pregnancy. Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo. Evaluating the Quality of Randomized Controlled Trials that Examine the Efficacy of Natural Health Products: A Systematic Review of Critical Appraisal Instruments A Phase II study of St. John's Wort for smoking cessation. [St. John's wort extract in the ambulatory therapy of depression. Attention and reaction ability are preserved]. INterpreting the Processes of the UMPIRE Trial (INPUT): protocol for a qualitative process evaluation study of a fixed-dose combination (FDC) strategy to improve adherence to cardiovascular medications Treatment of Somatoform Disorders With St. John's Wort: A Randomized, Double-Blind and Placebo-Controlled Trial
Hyperforin ( HYF ) has been discussed as a potential cause of the reduction in the bioavailability of numerous drugs seen with St John 's wort ( SJW ) comedication . This study compared the effects of 2 SJW preparations with high and low HYF content on the pharmacokinetics of cyclosporine ( INN , ciclosporin ) ( CSA ) St John 's wort is a popular over‐the‐counter dietary supplement and herbal remedy that has been implicated in drug interactions with several substrates of P‐glycoprotein . The effect of St John 's wort on P‐glycoprotein activity in vivo was examined with use of fexofenadine as selective probe drug BACKGROUND A continuation study of an extract of St. John 's wort ( Hypericum perforatum ) for depression was performed in follow-up to an acute study that found no significant difference between St. John 's wort extract and placebo . METHOD Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John 's wort extract in the acute-phase study ( phase 1 ) were continued on double-blind treatment with the same preparation for 24 weeks . Ninety-five subjects who did not respond to either St. John 's wort or placebo  were treated with an antidepressant for 24 weeks . RESULTS During antidepressant treatment , mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly ( p < .0001 ) , with no significant difference between St. John 's wort nonresponders and placebo nonresponders . Of the 17 subjects continued on treatment with St. John 's wort extract , 5 ( 29.4 % ) relapsed . CONCLUSIONS The subjects who did not respond to St. John 's wort extract or placebo in phase 1 were , by and large , not resistant to antidepressant treatment . This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects CONTEXT 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 . OBJECTIVE To compare the efficacy and safety of a st and ardized extract of St John 's wort with placebo in out patients with major depression . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States . PARTICIPANTS Two hundred adult out patients ( 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 . INTERVENTION Participants completed a 1-week , single-blind run-in of placebo , then were r and omly 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 . MAIN OUTCOME MEASURES 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 ) . RESULTS The r and om 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 ) . CONCLUSION In this study , St John 's wort was not effective for treatment of major depression Tacrolimus is an immunosuppressant approved for the prevention of rejection following transplantation and is a substrate for CYP3A and P-glycoprotein . A pharmacokinetic interaction between St. John 's wort ( antidepressant herbal product and inducer of CYP3A and P-glycoprotein ) and tacrolimus was evaluated in 10 healthy volunteers . The pharmacokinetics of tacrolimus were obtained from serial blood sample s collected following single oral doses ( 0.1 mg/kg ) prior to and during an 18-day concomitant St. John 's wort dosing phase ( 300 mg orally three times daily ) . Coadministration of St. John 's wort significantly decreased  tacrolimus AUC ( 306.9 microg.h/L + /- 175.8 microg.h/L vs. 198.7 microg.h/L + /- 139.6 microg.h/L ; p=0.004 ) and increased apparent oral clearance ( 349.0 mL/h/kg + /- 126.0 mL/h/kg vs. 586.4 mL/h/kg + /- 274.9 mL/h/kg ; p=0.01 ) and apparent oral volume of distribution at steady state ( 11.5 L/kg + /- 4.3 L/kg vs. 17.6 L/kg + /- 9.6 L/kg ; p=0.04 ) . St. John 's wort appears to induce  tacrolimus metabolism , most likely through induction of CYP3A and P-glycoprotein & NA ; Tricyclic antidepressants are the mainstay of treatment of painful polyneuropathy but can not be used in a substantial number of patients . St. John 's wort is a herbal antidepressant , which may act via mechanisms similar to the tricyclics . The aim of this study was to test if St. John 's wort would relieve  painful polyneuropathy . The study design was r and omized , double‐blind , placebo‐controlled and cross‐over . Fifty‐four patients were assigned to one of the two treatment sequences . The daily dose of St. John 's wort was three tablets each containing 900 & mgr;g totalhypericin . During the two treatment periods of 5 weeks duration , patients rated constant pain , lancinating pain paroxysms , touch‐evoked pain and pain on pressure by use of 0–10 point numeric rating scales . Forty‐seven patients – 18 diabetics and 29 non‐diabetics – completed the study . There was a trend of lower total pain score ( sum of the individual pain scores ) on St. John 's wort than on placebo ( median 14 vs. 15 , P=0.05 ) . None of the individual pain ratings were significantly changed by St. John 's wort as compared to placebo ( P=0.09–0.33 ) . Complete , good or moderate pain relief was experienced by nine patients with St. John 's wort and two with placebo ( P=0.07 ) . In conclusion , St. John 's wort has no significant effect on pain in polyneuropathy The popular herbal remedy St John 's wort is an inducer of cytochrome P450 ( CYP ) 3A enzymes and may reduce the efficacy of oral contraceptives . Therefore we evaluated the effect of St John 's wort on thedisposition and efficacy of Ortho‐Novum 1/35 ( Ortho‐McNeil Pharmaceutical , Inc , Raritan , NJ ) , a popular combination oral contraceptive pill containing ethinyl estradiol ( INN , ethinylestradiol ) and norethindrone ( INN , norethisterone ) Although St John 's wort ( Hypericum perforatum ) is one of the most widely used and studied herbal medicines for depression , less is known about its efficacy in anxiety disorders , in spite of the fact that patients with anxiety disorders are among the most likely to self-medicate using alternative treatments . Pharmacokinetic evidence for the serotonergic , domaminergic and GABAminergic activity of hypericum , and a recent successful open-label study , suggests that it may be effective for obsessive – compulsive disorder ( OCD ) . Sixty subjects were r and omized to 12 weeks of treatment with St John 's wort ( LI 160 ) or  matching placebo . Subjects with Hamilton Depression Scale scores of 16 or above were excluded . A flexible-dose schedule was utilized ( 600–1800 mg/day ) . The mean change on the Yale – Brown Obsessive – Compulsive Scale ( Y-BOCS ) with St John 's wort ( 3.43 ) was not significantly different than the mean change found with placebo ( 3.60 ) ( P=899 ) . No significant differences were found on any of the Y-BOCS subscales . The percentage of patients rated as ‘ much ’ or ‘ very much ’ improved at endpoint was not significantly different between St John 's wort ( 17.9 % ) and placebo ( 16.7 % ) ( P=0.905 ) . Only one patient from each group discontinued due to adverse events [ sinus infection ( St John 's wort ) ; confusion ( placebo ) ] . The results fail to support the efficacy of St John 's wort for OCD St. John 's Wort is a herbal therapy , shown to be effective in treating mild to moderate depression ; a disease common in women in their childbearing years . With a significant proportion of unplanned pregnancies , exposure to St. John 's Wort into pregnancy is expected to occur . The purpose of this study was to determine whether exposure to this agent in pregnancy is associated with major malformations . We prospect ively collected and followed subjects taking St. John 's Wort and compared them to a matched group of pregnant women taking other pharmacologic therapy for depression and a third group of healthy women , not exposed to any known teratogens . We obtained follow-up information on 54 St. John 's Wort exposed pregnancies and 108 pregnancies in the two comparator groups . Our results indicated that the rates of major malformations were similar across the three groups , with 5 % , 4 % and 0 % in the St. John 's Wort , disease comparator , and health group , respectively ( p=0.26 ) , This was not different that the 3 - 5 % risk expected in the general population . The live birth and prematurity rates were also not different among the three groups . Though further large scale studies are still needed , this first study on the effects of St. John 's Wort in human pregnancy does provide some evidence of fetal safety Many drugs are cosubstrates of cytochrome P450 ( CYP ) 3A and MDR1 ; furthermore , their disposition is markedly affected by pretreatment with inducing agents , including St John 's wort . Such drug interactions reflect induction of both proteins through a common mechanism involving the steroid X receptor/pregnane X receptor . However , the relative contributions of enhanced metabolism and efflux transport to the overall induction process are unknown St John 's wort(Hypericum perforatum ) is a popular over‐the‐counter dietary supplement and herbal remedy that has been implicated in drug interactions with substrates of several cytochrome P450 ( CYP ) isozymes . The effect of St John 's wort on CYP activity in vivo was examined with a probe drug cocktail This paper presents new data addressing two important controversies in psychiatry : the construct of Minor Depression ( MinD ) and the efficacy of St. John 's Wort for milder forms of depressive disorders . Data are from a three-arm , 12 week , r and omized clinical trial of investigating the efficacy of St. John 's Wort ( 810 mg/day ) , citalopram ( 20 mg/day ) , or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures , neither St. John 's Wort nor citalopram separated from placebo on change in depressive symptom severity , quality of life , or well-being . However , systematic assessment of potential adverse effects ( AEs ) led to three important observations : ( 1 ) prior to the administration of study compound , 60 % of subjects endorsed items that would be characterized as AEs once study compound was administered , ( 2 ) St. John 's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment , and ( 3 ) using a structured interview for identifying AEs at baseline and during treatment is informative . MinD was not responsive to either a conventional antidepressant or a nutraceutical , and both compounds were associated with a notable side effects burden . Other treatment approaches for MinD should be investigated The purpose of this project was to conduct a systematic review to identify instruments design ed to evaluate the quality of r and omized controlled trials ( RCTs ) of natural health products ( NHPs ) . Instruments were examined for inclusion of items assessing methods , identity and content of the NHP , generalizability of results and instructions for use . Online data bases , websites , textbooks and reference lists were search ed to identify instruments . Relevance assessment and data extraction of articles were completed by two investigators and disagreements were settled by the third investigator . Data were analyzed using descriptive statistics . Of the 4442 citations identified , 29 were potentially relevant with 16 meeting the criteria for inclusion . None of the instruments stated they were vali date d ; content in the four areas of interest varied considerably . The most common items included r and omization sequence generation ( 100 % ) , blinding ( 100 % ) , allocation concealment ( 75 % ) and participant flow ( 75 % ) . Only nine of the NHP instruments included at least one item to appraise the specific content of the NHP . The CONSORT Statement for Herbal Interventions most closely addressed the four areas of interest ; however , this instrument was specific for herbs . There is a need for the development of a vali date d instrument for assessment of the quality of RCTs that would be useful for herbs as well as other NHPs OBJECTIVES To examine the feasibility and efficacy of St. John 's Wort ( SJW ) for  smoking cessation .  DESIGN This one-arm Phase II study utilized an exact two-stage group sequential design with a 1-week run-in period between the start of SJW treatment and the design ated quit date . A total of 37 smokers ( ages 18 - 65 years , smoking > or = 10 cigarettes/day ) were started on SJW . Thirteen failed to make a verified quit attempt on the pre design ated date and were taken off study result ing in 24 evaluable subjects . SETTING Smokers completed clinic visits at a cancer center with interval telephone calls and mailings . INTERVENTION St and ardized SJW , 450 mg capsules taken orally twice daily along with cessation counseling messages . MAIN OUTCOME MEASURES Subjects completed vali date d surveys and a focused physical examination at baseline . Evaluable subjects were defined as those subjects who made a confirmed quit attempt on their " quit date " 1 week following initiation of SJW . Smoking status was determined through self-report and bioverification using carbon monoxide ( CO ) testing . RESULTS Among evaluable subjects , the 12-week quit rate was 37.5 % ( 9/24 ) . Quitters had no significant change in weight from baseline to 12-weeks cessation . Use of SJW was generally well tolerated . CONCLUSIONS Based upon these results ( which suggest that SJW may be effective in maintaining smoking cessation ) and the high compliance and few AEs , we conclude that SJW demonstrates feasibility for use in smoking cessation . If SJW proves to be effective in larger controlled studies , it could represent a less expensive , more readily accessible and well-tolerated agent to promote tobacco cessation METHOD In a placebo-controlled , r and omized , double-blind trial involving out patients with mild to moderately severe depression , an extract of St. John 's wort ( Hypericum ) , LI 160 , a herbal antidepressant was tested for efficacy and tolerability , as well as for possible negative effects on cognitive performance . RESULTS The responder rate to treatment with the extract was 66.6 % as compared with only 26.7 % with placebo . The treatment was very well tolerated ; only in two patients did transient minor side effects occur under LI 160 . No impairment of cognitive performance was observed : during the trial , Hypericum did not lead to any impairment of attention , concentration or reaction Introduction This paper describes a planned process evaluation of the Use of a Multidrug Pill In Reducing Cardiovascular Events ( UMPIRE ) trial , one of several r and omised clinical trials taking place globally to assess the potential of cardiovascular drugs as a fixed-dose combination ( polypill ) in cardiovascular disease prevention . A fixed-dose combination may be a promising strategy for promoting adherence to medication ; alleviating pill burden through simplifying regimens and reducing cost . This process evaluation will complement the UMPIRE trial by using qualitative research methods to inform underst and ing of the complex interplay of factors that underpin trial outcomes . Methods A series of semistructured , in-depth interviews with local health professionals and UMPIRE trial participants in India and the UK will be undertaken . The aim is to underst and their views and experiences of the trial context and of day-to-day use of medications more generally . The grounded theory approach will be used to analyse data and help inform the processes of the UMPIRE trial . Ethics and dissemination The study has received ethical approval for all sites in the UK and India where trial participant interviews will be undertaken . The process evaluation will help inform and enhance the underst and ing of the UMPIRE trial results and its applicability to clinical practice as well as shaping policy regarding strategies for improving cardiovascular medication adherence Objective : To investigate efficacy and safety of St. John 's wort ( SJW ) LI 160 in somatoform disorders . Methods : In a prospect i ve , r and omized , placebo-controlled , and double-blind parallel group study , 184 out patients with somatization disorder ( ICD-10 F45.0 ) , undifferentiated somatoform disorder ( F45.1 ) , and somatoform autonomic dysfunction ( F45.3 ) , but not major depression , received either 300 mg of SJW extract LI 160 twice daily or matching placebo for 6 weeks . Six outcome measures were evaluated as a combined measure by means of the Wei Lachin test : Somatoform Disorders Screening Instrument – 7 days ( SOMS-7 ) , somatic subscore of the HAMA , somatic subscore of the SCL-90-R , subscores “ improvement ” and “ efficacy ” of the CGI , and the global judgment of efficacy by the patient . Results : In the intention to treat population ( N = 173 ) , for each of the six primary efficacy measures as well as for the combined test , statistically significant medium to large-sized superiority of SJW treatment over placebo was demonstrated ( p < .0001 ) . Of the SJW patients , 45.4 % were classified as responders compared with 20.9 % with placebo ( p = .0006 ) . Tolerability of SJW treatment was equivalent to placebo . Conclusions : Administration of 600 mg of SJW extract LI 160 daily is effective and safe in the treatment of somatoform disorders , thereby confirming results from a previous study
Clinicians and patients should beware of possible decreases in the systemic bioavailability of conventional drugs when taken concomitantly with St John 's wort
OBJECTIVE To determine the method ological quality of clinical trials that examined possible interactions of St John 's wort with conventional drugs , and to examine the results of these trials .