The Tibetan herbal formula Padma Digestin in functional dyspepsia: an open-label study.

BACKGROUND: The etiology of functional dyspepsia (FD) is multi-factorial. Its prevalence is high and it considerably impairs the patients' quality of life. The treatment options are limited. Padma Digestin, a multi-herbal formula from Tibetan Medicine, is traditionally used in malabsorption and dyspeptic symptoms as they do occur in FD, but as yet no clinical data exist on the formula. The aim of this study was to evaluate the safety, tolerability, and efficacy of Padma Digestin in patients with FD in a prospective, open, clinical phase III trial. PATIENTS AND METHODS: Patients were recruited by general practitioners, internists, and gastroenterologists and treated with 2 × 3 capsules of Padma Digestin daily for 6 weeks. Dyspeptic symptoms were analyzed using the Domestic/International Gastroenterology Surveillance Study (DIGEST) questionnaire extended by the 2 symptoms stomach cramps and lack of appetite. The quality of life was assessed using the Psychological General Well-Being Index (PGWBI-S) questionnaire (short version). RESULTS: 37 patients were admitted and efficacy could be assessed in 31. In the overall efficacy assessment, the Padma Digestin treatment led to a statistically highly significant reduction of the respective most bothersome symptom scores regarding frequency, severity, and impairment of daily activities (p < 0.01). The treatment also led to significant improvements of the individual symptoms of postprandial fullness, nausea, localized and diffuse epigastric pain, stomach cramps, and lack of appetite. The onset of improvement was after a median of 7 days; time until disappearance of the symptoms was after a median of 22 days. The global efficacy and tolerability were rated as good or very good by the doctors and the patients in 84% and 78%, respectively. The PGWBI-S increased from 55 ± 19.5% to 70.5 ± 15.5%, which is nearly the normal value (73.5 ± 15.4%). As for safety, 11 patients reported a total of 17 adverse events (AE), 1 of which was serious but unrelated to the study medication. The AE were mild or moderate. The safety laboratory data showed no statistically significant or otherwise relevant changes. CONCLUSIONS: The results show that the formula Padma Digestin has a high tolerability and efficacy in FD symptoms and positively influences psychological well-being and thus quality of life. It therefore represents a much needed extension of the therapeutic repertoire in FD.

Preliminary data of a HAMD-17 validated symptom scale derived from the ICD-10 to diagnose depression in outpatients.

BACKGROUND: In outpatient settings diagnostic classification of depressive symptoms is mostly descriptive based on ICD-10. Depending on clinical experience and consultation time, diagnosis can be verified by validated scales. However, physicians working in primary care are familiar with ICD-10 criteria. Therefore, the aim of the present study was to examine the feasibility of the validation of an ICD-10-derived symptom scale for depression. METHODS: For this preliminary trial we generated a symptom scale derived 1:1 from the diagnostic criteria for depression given in the ICD-10 with 10 items. The Hamilton Rating Scale for Depression (HAMD-17) was used as reference in a population of 226 outpatients suffering from depressive symptoms. Correlation between scales as well as sensitivity and specificity of the ICD-10 scale were calculated. RESULTS: The generated ICD-10 symptom scale for depression could be analyzed in 219 patients and showed a significant and strong correlation with the HAMD-17 (p < 0.0001; ρ = 0.75). The best tradeoffs between specificity and sensitivity of the ICD-10 score were found at 10 points for the lower and 14 points for the upper cut-off. Overall sensitivity and specificity was 76.7 and 88.6%. Almost two thirds (i.e. 65.3%) of the patients were correctly classified by the ICD-10 scale. CONCLUSION: The ICD-10 symptom scale examined in the current population was found to have fair correlation with the HAMD-17 as well as, in face of the limited variance of the patients' condition, acceptable sensitivity and specificity. Therefore, this preliminary study showed that the ICD-10-derived symptom scale seems appropriate to be investigated in a thorough validation trial.

Phytodolor® in musculoskeletal disorders: re-analysis and meta-analysis.

BACKGROUND: Treatment of rheumatic or musculoskeletal disorders (MD) is multi-disciplinary and includes herbal analgesics. Although already reviewed, no quantitative evaluation of efficacy and safety of the herbal combination Phytodolor® (STW1) is available. METHODS: We searched in databases and contacted authors and the manufacturer to identify randomized controlled trials (RCTs) examining STW1 in patients with MD. We made a reanalysis of raw data of eligible published and unpublished RCTs and pooled the results for meta-analysis according to Cochrane guidelines and intention-to-treat. Primary outcome measure was patient global assessment of efficacy, secondary outcome measure was pain at rest and on movement. Results were stratified according to treatment groups. RESULTS: Patient data of 11 RCTs were eligible for pooling. In the entire population, STW1 was significantly superior compared to placebo in patients' global assessment of efficacy (group difference for rating very good/good: 20%; placebo 48.9% and STW1 69.1%; p < 0.001; OR 0.43; 95% CI 0.28-0.65) and in the subpopulation 'other rheumatic diseases' (placebo 45.4%; STW1 72.3%; p < 0.001; OR 0.32; 95% CI 0.2-0.52), but not in the subpopulation 'gonarthrosis'. STW1 did not differ significantly compared to non-steroidal anti-inflammatory drugs (NSAIDs), neither in the entire population nor the subpopulations. Similar results were found for pain at rest and on movement. No serious adverse events (AE) but minor AE were reported (placebo 8.1%; STW1 14.2%; NSAIDs 18.9%). CONCLUSION: According to the analysed data, STW1 showed a better pain reduction than placebo in patients with pain due to MD, probably equivalent to NSAIDs, and was well tolerated.

A hypericum extract in the treatment of depressive symptoms in outpatients: an open study.

BACKGROUND: Extracts of Hypericum perforatum have demonstrated in randomized trials (RCTs) to be effective in mild to moderate depressive episodes. However, as their use in daily practice may differ from that in RCTs we have conducted a study to achieve a better estimate of the range and frequency of adverse drug reactions (ADR) and the efficacy. PATIENTS AND METHODS: In an observational study in Germany, adult outpatients with depressive syndrome were treated with an extract of St. John's Wort. Study duration was 12 weeks, with control visits every 4 weeks. Besides anamnestic data, the variables assessed were: evolution of ICD-10 derived symptom score, Global Clinical Impression scale (GCI), and tolerability. RESULTS: 1,778 patients from 304 centers participated in the study (mean duration of disorder 7.3 +/- 18.9 months), and 1,541 patients completed it. At the last control visit the ICD-10 sum score had dropped by 63.1% and the proportion of patients described as 'normal to mildly ill' (GCI-s) had increased from 21.6% at admission to 72.4%. Regarding the GCI-i, 77% of the patients had improved 'very much' or 'much' at the last visit. This was consistent with their self-assessment (76%). Lower age and shorter duration of the disorder were associated with significantly better outcomes. The incidence of ADRs was 3.54% and had been decreasing continuously from the first control visit onwards; serious ADRs did not occur. CONCLUSIONS: The herbal drug was well tolerated, and no new or serious ADR were identified. In view of the limitations inherent to the study design, it can be concluded that extracts of St. John's Wort are effective as an antidepressant in the management of depression in daily practice.

An updated systematic review with meta-analysis for the clinical evidence of silymarin.

BACKGROUND: The potential benefit of silymarin (special extract from the fruits of Silybum marianum) in the treatment of liver diseases remains a controversial issue. METHODS: For this systematic review electronic databases identified 65 papers for the search terms silymarin, silibinin, silicristin or milk thistle and clinical trial. Only 19 complied with the criteria'double-' or 'single-blind'. These publications were analysed from a clinical point of view and meta-analytic calculations were performed. RESULTS: The clinical evidence ofa therapeutic effect of silymarin in toxic liver diseases is scarce. There is no evidence of a favourable influence on the evolution of viral hepatitis, particularly hepatitis C. In alcoholic liver disease, comparing with placebo, aspartate aminotransferase was reduced in the silymarin-treated groups (p = 0.01) while alkaline phosphatase was not. In liver cirrhosis, mostly alcoholic, total mortality was 16.1% with silymarin vs. 20.5% with placebo (n.s.); liver-related mortality was 10.0% with silymarin vs. 17.3% with placebo(p = 0.01). CONCLUSIONS: Based on the available clinical evidence it can be concluded - concerning possible risks /probable benefits - that it is reasonable to employ silymarin as a supportive element in the therapy of Amanita phalloides poisoning but also (alcoholic and grade Child 'A') liver cirrhosis. A consistent research programme, consolidating existing evidence and exploring new potential uses,would be very welcome.

Iron(III)-hydroxide polymaltose complex in iron deficiency anemia / review and meta-analysis.

Iron(III)-hydroxide polymaltose complex (IPC) is an iron preparation with non-ionic iron and polymaltose in a stable complex. The usefulness of IPC in the treatment of iron deficiency anemia (IDA) has recently been a topic of much debate. By reviewing the published literature an overview is provided of the existing comparative evidence vs. ferrous sulfate as reference. For this purpose the standard methods and criteria as described by the Cochrane group are employed. The aim was to establish whether there are differences concerning efficacy (primary end-point: hemoglobin after approx. 2 months of treatment) and concerning safety (number of patients with adverse drug reactions [ADRs]). From an initial group of 14 comparative trials identified, 6 comparative studies (1 double blind) conducted in adults could be retained for analysis. Four pediatric studies initially selected had to be rejected because of heterogeneity of data at baseline. In adults (319 IPC, 238 ferrous sulfate) at the end of the study period (8-13 weeks) the mean hemoglobin values were 12.13 +/- 1.19 g/dl with IPC vs. 11.94 +/- 1.84 g/dl with ferrous sulfate (weighted mean difference WMD = 0.01 [95% CI -0.23, 0.21] g/dl). Not all studies reported on ferremia (higher with IPC), transferrin saturation (no difference) or ferritin (lower with IPC). Adverse drug reactions were reported less frequently with IPC (14.9%) than with ferrous sulfate (34.1%; p < 0.001), particularly upper digestive troubles, stained teeth and diarrhea. The meta-analysis of studies conducted in adult patients with iron deficiency anemia, comparing IPC with ferrous sulfate in equivalent doses, showed that the two compounds attained similar hemoglobin levels, thus suggesting similar efficacy. The tolerance of IPC in adults was clearly better than that of ferrous sulfate; the differences were also significant for the individual adverse reactions. This probably reflects a better risk/benefit ratio of IPC in adults. Properly conducted randomized controlled trials, particularly in pediatrics, are needed.

An updated systematic review of the pharmacology of silymarin.

BACKGROUND: Recent years have seen an explosion of scientific papers that deal with drugs from the fruits of milk thistle and its active substances silymarin (standardized mixture of flavonolignanes), thus justifying an updated systematic review. METHODS: Electronic databases identified silymarin, silibinin, silicristin or milk thistle as descriptors in >700 papers (34% published in last 5 years; 92% dealt with animal pharmacological). Only papers adequately reporting on experimental conditions, dosing, variables tested and statistics were analysed. RESULTS: Silymarin was found to modify specifically the functions related to various transporters and receptors located in the cell membranes; that is, organic anion uptake transporter peptides (OATP), ABC transporters (P-gp), bile salt export pump, as well as TNF-alpha-dependent and possibly selectin-dependent phenomena. In the cytoplasm, some antioxidant properties and the inhibition of the lipoxygenase pathway seem quite selective and could concur to the antitoxic effects. Some effects like the inhibition of inducible nitric-oxide synthase, of nuclear factor kappa B, and reduction of collagen synthesis are indicative of DNA/RNA-mediated effects. Several studies using 'in vitro' and 'in vivo' cancer models suggest a potential of silymarin in such diseases. Topical and systemic silymarin has skin protective properties against UV-induced damage in epidermis and causes an up-regulation of tumour-suppressor genes p53- and p21CIP1. There were no data on hepatic viral replication, viremia or spontaneous tumours in the data examined. CONCLUSIONS: Data presented here do not solve the question about the complex mechanism(s) of action of the medicinal herbal drug silymarin. Silymarin may be a natural multi-functional and multi-target drug.

Treating intermittent claudication with Tibetan medicine Padma 28: does it work?

Herbal drugs are being increasingly used in medical practice, often without appropriate scrutiny of their safety and efficacy. The medicinal product Padma 28 is a fixed combination with Tibetan origin, used in Europe since the 1960s for the symptomatic treatment of circulatory disorders, including those of peripheral arterial occlusive disease (PAOD). We have conducted an analysis of all available data on this herbal drug from published literature as well as from original data we obtained from contacting the authors of published papers, reports and the manufacturer. A total of 19 trials have reported on 2084 patients to date, 444 of whom were in six controlled clinical studies on PAOD. A meta-analysis of five trials showed Padma 28 to increase walking distance by >100m in 18.2% of the patients with verum, versus 2.1% with placebo (P<0.001; odds ratio: 10 [95% CI 3.03, 33.33]; RR: 0.12; number needed to treat=6.2). The safety profile appears to be favourable. Available evidence shows that Padma 28 provides significant relief from PAOD-related symptoms (i.e. walking distance), probably of the same order of magnitude as other employed medications. However, larger confirmatory RCTs are desirable.

Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis.

BACKGROUND: The herbal formula BNO-101 (containing Gentianae radix, Primulae flos, Rumicis herba, Sambuci flos and Verbenae herba; ratio 1:3:3:3:3) has been widely employed as a 'mucoactive' agent in Germany for 70 years for the symptoms of respiratory infections. This paper reviews the clinical evidence of BNO-101 in sinusitis. METHODS: The systematic search identified 22 studies with BNO-101. Out of these, 6 controlled trials on sinusitis were reassessed according to predefined criteria. 4 trials had almost identical designs and could be examined by meta-analysis. RESULTS: The database comprised approximately 900 patients, mostly young adult males. After 2 weeks of treatment, verum was significantly superior to placebo (2 RCTs, 159 vs. 160 patients, both add-on to antibacterial treatment). The benefit regards the patients' assessment ('cured': verum = 61.1%, placebo = 34.5%), reduction of drain obstruction, headache and radiological signs (all p < 0.05). Comparing BNO-101 to ambroxol (2 RCTs, 151 vs. 150 patients, add-on to antibacterials in 13% of the cases) the patients' assessment after 2 weeks showed no difference, although it favoured BNO-101 in chronic cases ('cured' BNO-101 = 37.1%, ambroxol = 12.5%; p < 0.05). It also favoured BNO-101 concerning pyorrhoea and headache (p < 0.05). No significant differences were reported in 2 open randomised trials vs. N-acetyl-cysteine and vs. the herbal product Myrtol std. CONCLUSIONS: BNO-101, combined with standard antibacterial therapy, significantly reduces the acute symptoms and signs of sinusitis. The effects are of the same order of magnitude as observed with other mucoactive agents. In the trials investigated BNO-101 had a favourable risk/benefit ratio, with an incidence of adverse events similar to placebo.

[Efficacy and safety of Padma 28 in peripheral arterial occlusive disease]. / Wirksamkeit und Sicherheit von Padma 28 bei peripherer arterieller Verschlusskrankheit.

BACKGROUND: The multicompound herbal drug Padma 28 is based on a formula from Tibetan Medicine and has been used in Switzerland for over 30 years in the symptomatic treatment of circulatory disorders including intermittent claudication. OBJECTIVE: What is the current evidence regarding the clinical efficacy and safety of this drug in patients with peripheral arterial occlusive disease(PAOD)? MATERIALS AND METHODS: Electronic databases were searched (each from inception to fall 2005) as well as the reference lists of the relevant articles. RESULTS: 14 articles were found including 6 published studies, 1 un-published study, 6 double publications and 1 meta-analysis. Six studies analyzed maximum walking distance, 5 of these showed a significant increase. The pooled data of the meta-analysis confirmed a significant and clinically relevant increase of the maximum walking distance by more than 100 m in about 1 out of 5 patients. Serious adverse events were not related to verum, non-serious adverse events were equally frequent as under placebo. CONCLUSIONS: The evidence available shows that the multi-target therapy with Padma 28 provides statistically significant and clinically relevant relief from PAOD-related symptoms, i.e. an increased walking distance.