The present drug-drug interaction study investigates whether single or repeated doses of 240 mg
extract EGb 761
alter the pharmacokinetics or pharmacodynamics of rivaroxaban in healthy subjects. This ...was a single-centre, two-period, fixed-sequence trial. In Period 1, rivaroxaban was taken alone. In Period 2, rivaroxaban was given on the first and last of 8 days of EGb 761
treatment. Plasma concentrations of rivaroxaban and anti-Factor Xa activity were determined until 48 h after each rivaroxaban intake. The data of forty-one healthy subjects (25 males, 16 females) aged 21-70 years were evaluable. Geometric mean ratios (90% confidence intervals) for rivaroxaban administered concomitantly with a single or multiple doses of EGb 761
vs. rivaroxaban administered alone were 97.97 (91.78, 104.58) and 96.78 (90.67, 103.31) for maximum concentration (C
), 98.55 (94.43, 102.84) and 97.82 (93.73, 102.08) for area under the concentration-time curve (AUC
) of rivaroxaban in plasma (primary endpoints), 98.19 (92.00, 104.80) and 99.78 (93.43, 106.55) for maximum effect (E
), 99.46 (93.63, 105.66) and 99.12 (93.25, 105.35) for area under the effect curve (AUEC
). All 90% confidence intervals were within the prespecified range of 80%-125%. Neither adverse events related to haemorrhages nor clinically significant findings in haematology or coagulation parameters were observed. The treatments were safe and well-tolerated. Single and repeated doses of EGb 761® neither affect plasma concentrations of rivaroxaban nor anti-Factor Xa activity in healthy subjects.
Abstract Mixed anxiety and depressive disorder (MADD; ICD-10 F41.2) is a condition characterized by subsyndromal symptoms of anxiety and depression, neither of which are clearly predominant. Silexan ...has been demonstrated to be efficacious in subsyndromal and syndromal anxiety disorders and co-morbid depressive symptoms. In this study 318 adult out-patients with MADD according to ICD-10 criteria, a total score ≥18 points on the Hamilton Anxiety Rating Scale (HAMA), and at least moderately severe anxious and depressed mood were randomized and received 1×80 mg Silexan or placebo in double-blind fashion for a scheduled period of 70 days. Primary outcome measures were the HAMA and Montgomery Åsberg Depression Rating Scale (MADRS) total score changes between baseline and treatment end. The HAMA total score decreased by 10.8±9.6 points for Silexan and by 8.4±8.9 points for placebo (treatment group difference: p <0.01, one-sided; ANCOVA with factors for treatment and centre and the baseline value as covariate), and total score decreases of 9.2±9.9 and 6.1±7.6 points, respectively, were observed for the MADRS ( p <0.001). Compared to placebo, the patients treated with Silexan had a better over-all clinical outcome and showed more pronounced improvements of impaired daily living skills and health related quality of life. Eructation was the only adverse event with a substantially higher incidence under Silexan. The study thus demonstrates that Silexan is efficacious and safe in the treatment of MADD.
The anxiolytic efficacy of the orally administered lavender oil preparation Silexan was investigated in generalized anxiety disorder (GAD) in comparison to placebo and paroxetine. In this randomized, ...double-blind, double-dummy trial 539 adults with GAD according to DSM-5 criteria and a Hamilton Anxiety Scale (HAMA) total score ⩾18 points participated and received 160 or 80 mg Silexan, 20 mg paroxetine, or placebo once daily for 10 wk. The primary efficacy endpoint was the HAMA total score reduction between baseline and treatment end. The HAMA total score decreased by 14.1 ± 9.3 points for Silexan 160 mg/d, 12.8 ± 8.7 points for Silexan 80 mg/d, 11.3 ± 8.0 points for paroxetine, and 9.5 ± 9.0 points for placebo (mean ± s.d.). Silexan 160 and 80 mg/d were superior to placebo in reducing the HAMA total score (p < 0.01) whereas paroxetine showed a trend towards significance (p = 0.10) in the full analysis set. The difference between paroxetine and placebo was more pronounced in the analysis of observed cases (HAMA total score reduction: p < 0.01). In the Silexan 160 mg/d group 73/121 patients (60.3%) showed a HAMA total score reduction ⩾50% of the baseline value and 56 (46.3%) had a total score <10 points at treatment end, compared to 70/135 (51.9%) and 45 (33.3%) for Silexan 80 mg/d, 57/132 (43.2%) and 45 (34.1%) for paroxetine, and 51/135 (37.8%) and 40 (29.6%) for placebo. In addition, Silexan showed a pronounced antidepressant effect and improved general mental health and health-related quality of life. Incidence densities of adverse events (AEs) were 0.006 AEs/d for Silexan 160 mg/d, 0.008 AEs/d for 80 mg/d, 0.011 AEs/d for paroxetine, and 0.008 AEs/d for placebo. In GAD Silexan is more efficacious than placebo. AE rates for Silexan were comparable to placebo and lower than for the active control paroxetine.
This cocktail study evaluated the interaction potential of the oral lavender oil preparation silexan with major P450 (cytochrome P450) enzymes.
Sixteen healthy male or female Caucasians completed ...this double-blind, randomized, 2-fold crossover study. Silexan (160 mg) or placebo were administered once daily for 11 days. Additionally, on day 11 of both study periods, 150 mg caffeine (CYP1A2), 125 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan-HBr (CYP2D6), and 2 mg midazolam (CYP3A4) were administered orally. Formal interaction was excluded if the 90% confidence interval (CI) for the silexan over placebo ratios for phenotyping metrics (primary: AUC(0-t)) was within a 0.70-1.43 range.
According to the AUC(0-t) comparisons, silexan had no relevant effect on CYP1A2, 2C9, 2D6, and 3A4 activity. Secondary phenotyping metrics confirmed this result. Mean ratios for all omeprazole-derived metrics were close to unity. The 90% CI for the AUC(0-t) ratio of omeprazole but not for omeprazole/5-OH-omeprazole plasma ratio 3 hours post-dose or omeprazole/5-OH-omeprazole AUC(0-t) ratio (secondary CYP2C19 metrics) was above the predefined threshold of 1.43, probably caused by the inherent high variability of omeprazole pharmacokinetics. Silexan and the phenotyping drugs were well tolerated. Repeated silexan (160 mg/day) administration has no clinically relevant inhibitory or inducing effects on the CYP1A2, 2C9, 2C19, 2D6, and 3A4 enzymes in vivo.
The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in ...two doses.
The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS 5570 600 mg/day, 127 to WS 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination.
After 6 weeks of treatment, mean +/- standard deviation decreases in HAM-D total scores of 11.6 +/- 6.4, 10.8 +/- 7.3, and 6.0 +/- 8.1 points were observed for the WS 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS 5570 groups were statistically superior to placebo. Significantly more patients in the WS 5570 treatment groups than in the placebo group showed treatment response and remission. WS 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS 5570 1200 mg/day group than the WS 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations.
Hypericum perforatum extract WS 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS 5570 groups for the treatment of mild to moderate major depression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The anxiolytic effect of Silexan, a patented active substance with an essential oil produced from Lavandula angustifolia flowers, was investigated in patients with anxiety-related ...restlessness and disturbed sleep. 170 out-patients with a diagnosis of restlessness (ICD-10 R45.1), a Hamilton Anxiety Scale (HAMA) total score ≥18 points and ≥2 points for HAMA items ‘Tension’ and ‘Insomnia’ participated in this randomized, double-blind trial and received 80 mg Silexan or placebo once daily for 10 weeks. Patients with clinically important other psychiatric or neurological disorders potentially interfering with the assessment of treatment efficacy were excluded. Outcome variables were the HAMA as well as the Pittsburgh Sleep Quality Index (PSQI), the Zung Self-rating Anxiety Scale, a State Check inventory and the Clinical Global Impressions questionnaire. In the Silexan group the HAMA total score decreased from an average of 25.5±6.0 points at baseline to 13.7±7.0 points at treatment end, compared to a decrease from 26.5±6.1 to 16.9±9.8 for placebo, corresponding to decreases of 12.0 and 9.3 points (marginal means), respectively (group difference: p =0.03, ANCOVA with factor treatment and baseline value as covariate). In all outcome measures the treatment effect of Silexan was more pronounced than with placebo. According to the HAMA, 48.8% and 33.3% of the patients were responders (Silexan, placebo; reduction ≥50%; p =0.04) and 31.4% and 22.6% achieved remission (HAMA<10; p =0.20). 33.7% (Silexan) and 35.7% (placebo) of the participants reported adverse events. The study confirms the calming and anxiolytic efficacy of Silexan.
Summary
We review the data on the efficacy and tolerability of silexan, a novel preparation from lavender oil for oral use, in the treatment of anxiety disorders and related condition with particular ...attention to subthreshold generalized anxiety disorder (GAD). Three randomized, double-blind clinical trials were identified which investigated the efficacy of silexan in subsynromal anxiety disorder (
vs.
placebo; 10 weeks' treatment), in GAD (
vs.
lorazepam; 6 weeks), and in restlessness and agitation (
vs.
placebo; 10 weeks) according to DSM-IV and ICD-10 criteria. All trials assessed the participants' anxiety levels using the Hamilton Anxiety Scale (HAMA). Across all trials 280 patients were exposed to silexan 80 mg/day, 37 were treated with lorazepam 0.5 mg/day and 192 received placebo. Average within group HAMA total scores at baseline ranged between 24.7 and 27.1 points. Patients treated with silexan showed average HAMA total score decreases by between 10.4 ± 7.1 and 12.0 ± 7.2 points at week 6 and by between 11.8 ± 7.7 and 16.0 ± 8.3 points at week 10. In GAD silexan and lorazepam showed comparable HAMA total score reductions (90% CI for mean value difference: −2.3; 2.8 points).
Subthreshold psychiatric disorders do not fully meet the diagnostic criteria of syndromal disorders but may be associated with comparable disability. To investigate the anxiolytic effect of Silexan, ...an active substance from lavender oil for oral administration, in patients with subthreshold anxiety, a meta-analysis that included all published trials with Silexan in this indication was performed. Three randomised, placebo-controlled trials in subthreshold anxiety disorders (anxiety disorder not otherwise specified, restlessness and agitation, mixed anxiety and depressive disorder) were included. Eligible participants with a baseline Hamilton Anxiety Rating Scale (HAMA) total score ≥ 18 points received 1 × 80 mg/day Silexan or placebo for 10 weeks. Outcomes included the HAMA, the Pittsburgh Sleep Quality Index, the Zung Self-rating Anxiety Scale, the Clinical Global Impressions questionnaire and the SF-36 health status inventory. Data were analysed using meta-analysis based on pooled raw data of individual patients (random effects models). A total of 697 patients were assessed for efficacy. Silexan was superior to placebo in reducing the HAMA total score during 10 weeks’ treatment mean value difference, 95% confidence interval: 3.83 (1.28; 6.37) points. Superiority was comparably pronounced for psychic and somatic anxiety as well as for observer- and self-rated anxiety. Silexan had a beneficial effect on sleep (secondary to the anxiolytic effect) without causing sedation and improved the patients’ health-related quality of life. Adverse event incidence in both treatment groups was comparable risk ratio: 1.06 (0.85; 1.33). Silexan has a significant and clinically meaningful anxiolytic effect in subthreshold anxiety. The results cannot be generalised to other lavender oil products.
This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with
. The reported capacity of
to strengthen the organism against stress and its good ...tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with
dry extract in this target group.
The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg
extract (WS
1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales.
The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day.
The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout symptoms when treated with
. During administration of the study drug over the course of 12 weeks, a wide range of outcome measures associated with the syndrome clearly improved.
The results presented provide an encouraging basis for clinical trials further investigating the clinical outcomes of
extract in patients with the burnout syndrome.
Rhodiola rosea extract is widely used to alleviate stress and improve cognition and mental resources. A total of 50 adult participants were treated with 2 × 200 mg R. rosea extract (Rosalin®, WS® ...1,375) for 12 weeks and were subjected to a neuropsychological test battery as well as an event‐related brain potential measurement in a dual task paradigm prior to administration, after 6 weeks and after 12 weeks. The study followed a single‐arm open‐label design. Reaction times improved for the attention network task (ANT), the Go/Nogo task, and the divided attention task. Moreover, the orienting effect and the executive effect in the ANT showed an improvement. The P3 component in a dual task paradigm was increased in amplitude. The results of this pilot study show an improvement of mental speed and moreover, suggest improved mental resources. As the current study is single‐armed these findings need to be replicated in a double‐blind placebo controlled study.
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