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Herbal pharmaceuticals in medical practice are similarly used as chemically well defined drugs. Like other synthetical drugs, they are subject to pharmaceutical legislature (AMG) and EU directives. It is to differentiate between phytopharmaceuticals with effectiveness of proven indications and traditional registered herbal medicine. Through the Health Reform Act January 2004 and the policy of the Common Federal Committee (G-BA)on the contractual medical care from March 2009--with four exceptions--Non-prescription Phytopharmaka of the legal Health insurance is no longer (SHI) refundable and must be paid by the patients. The result is that more and more well-established preparations disappear from the market. This article gives an overview of practical relevant indications for herbal medicines, which according to its licensing status, the scientific assessment by the Cochrane Collaboration and the Institute for Quality and Efficiency in Health Care (IQWiG) and evidence-based Medicine (EBM)/ meta-analyzes as an alternative to synthetics can be used.

Introduction: The herbal medicinal product kava-kava, used for treating anxiety disorders, was assessed positively by the Cochrane Review. However, it was withdrawn from the market in Switzerland and Germany due to cases of liver failure and 'unproven' efficacy., Methods: A protocol for the meta-analysis based on patient source data was written, a literature search was done, and six placebo-controlled, randomized trials with the kava extract WS1490 were identified. The endpoints were the change in HAMA during treatment (continuous and binary)., Results: WS1490 has an effective success rate of OR=3.3 (95% confidence interval of 2.09-5.22) in patients with non-psychotic anxiety disorders. The continuous outcome supports this result: mean improvement with WS1490 by 5.94 (95% confidence interval -0.86 to 12.8) points on the HAMA scale better than placebo. Kava seems to be more effective in females and in younger patients., Discussion: This meta-analysis has no publication bias, no remarkable heterogeneity and is based on trials with high methodological standards. It is concluded that WS1490, and possibly other kava extracts, are effective. Therefore they remain alternatives to benzodiazepines, selective serotonin re-uptake inhibitors (SSRIs) and other antidepressants in the treatment of non-psychotic anxiety disorders., (Copyright 2005 John Wiley & Sons, Ltd.)

The bioavailability of beta-aescin--the main active constituent of horse chestnut seed extract--in a nonretarded test medication in comparison with that in a retarded reference formulation was evaluated in 2 randomized crossover clinical trials involving 18 healthy volunteers each. Serum concentration/time curves derived under steady-state conditions and pharmacokinetic parameters measured during both studies showed no significant difference between absorption rates for the retarded versus nonretarded preparation. In the first study, investigators found a test-to-reference ratio of 1.06 (90% confidence interval [CI] range: 99-113) for the area under the curve (AUC; the primary outcome measure). Absorption rates were diminished during the night compared with daytime rates for both study preparations. In the second study, using AUC and maximum concentration (Cmax) as the primary characteristics, investigators analyzed bioavailability based on the mean of 2 consecutive daytime periods and obtained estimates of 1.07 for AUC (90% CI range: 0.96-1.19) and 1.05 for Cmax (90% CI range: 0.90-1.21). Bioequivalence of the test and reference drug preparations was thus established according to the Note for Guidance on the Investigation of Bioavailability and Bioequivalence. Both treatments were equally well tolerated.

Independent, double-blinded, randomized, placebo-controlled studies using sublingual/oral administration of D-camphor, an extract from fresh crataegus berries, and a combination of the two (CCC) yielded the following results: Both the D-camphor and the extract from fresh crataegus berries, the components of CCC, contribute to the pressoric effects of the combination. The underlying hemodynamic mechanisms can be attributed to an increase in total peripheral resistance induced by an increased tone of the arterioles with both components and the effect of crataegus is intensified by an additional direct positive action on cardiac performance. Conceivably, the D-camphor component is the main factor in inducing the rapid initial effect, whereas the extract from fresh crataegus berries adds a long-lasting effect. For CCC, a dose-dependent increase in supine blood pressure and prevention of orthostatic fall in blood pressure following tilt table-induced orthostasis in patients with orthostatic dysregulation was demonstrated as well. The effect revealed a very rapid onset of action within 1 min following administration, confirming the traditional use in emergency situations such as orthostatic (pre)syncope. Thus, these studies show that CCC, depending on the pressoric activity of its two mono-components, exerts a significant effect that counteracts an orthostatic fall in blood pressure and thereby provides a rationale for its application that reemphasizes the decades-long usefulness of this phyto-combination.

An aqueous decoction of Piper methysticum has been used since centuries of Pacific Island at social religious-ceremonial and social events without hepatotoxic side effects in contrast to the speculation on industrial Kava preparations. It was assumed that the traditional non-alcoholic drink contains a spectrum of other constituents compared to the acetonic and ethanolic extracts. The TLC-analysis demonstrates, however, that under qualitative aspects there is no difference between aqueous and acetonic and ethanolic extracts respectively.

Herbal medicinal products (HMP) contain exclusively herbal drugs or herbal drug preparations (HDP) and are a complex mixture of different compounds, which may act in an agonistic, synergistic, complementary, antagonistic or toxic way. A specific scientific challenge is for methods to prone the bioequivalence of herbal drug preparations (HDP). Depending on the type of herbal drug preparations, different approaches are possible. If the constituents responsible for therapeutic activity are known, the concept of essential similarity used with chemically defined substances can be fully applied. For extracts with unknown active markers, data on defined chemical constituents are useful for control purposes (charge conformity), but not sufficient to prove bioequivalence. In this case bioassays or pharmacological studies, which measure therapeutically relevant activity, should be used. A phytogeneric is only comparable to the innovator preparation under the following conditions: (i) pharmaceutical equivalence (standardization), (ii) biopharmaceutical equivalence (in vitro dissolution), (iii) bioequivalence with different endpoints (in vitro model, animal model) or (iv) clinical study. An uncritical substitution of herbal drug preparations without considering these scientific criteria should be avoided., (Copyright 2002 John Wiley & Sons, Ltd.)

In order to test the efficacy of a combination of natural D-camphor and an extract of fresh crataegus berries (Korodin Herz-Kreislauf-Tropfen) on orthostatic hypotension, two similar, controlled, randomized studies were carried out in a balanced crossover design in 24 patients each with orthostatic dysregulation. The camphor-crataegus berry combination (CCC) was orally administered as a single regimen in 3 different dosages of 5 drops, 20 drops and 80 drops; a placebo with 20 drops of a 60% alcoholic solution served as control. Orthostatic hypotension was assessed with the tilt table test before and after medication. Source data of both studies were pooled and meta-analytically evaluated for all 48 patients. CCC drops decreased the orthostatic fall in blood pressure versus placebo, as almost uniformly established at all times by mean arterial pressure and diastolic blood pressure. Mean arterial pressure demonstrated the very fast onset of action by a clearly dose-dependent statistically significant effect even after 1-minute orthostasis. Increase of mean arterial pressure as compared to the orthostasis test before medication was on average 4.5 mmHg. CCC affected diastolic blood pressure after 1 minute of orthostasis in all dosages as compared to placebo. A statistically significant effect of the highest dose of 80 drops on diastolic blood pressure could be demonstrated after 1-, 3-, and 5-minute orthostasis. The hemodynamic findings of a stabilizing effect on arterial pressure in orthostasis corroborate the long-term medical experience with CCC and justify the indication orthostatic hypotension.

During the last decade, there has been an explosive growth of research concerning the extract of Ginkgo biloba termed Egb 761. In experimental studies, animal studies and clinical studies Ginkgo biloba has shown a similar pharmacological potency and clinical efficacy like synthetic defined drugs in the therapy of reduced cerebral performance. Ginkgo biloba special extract Egb 761 is a standardized and highly purified extract of Ginkgo leaves. Among the active constituents are the ginkgo-flavone glycosides and the terpene-lactones (ginkgolides, bilobalide). The multifactorial principle of action of Ginkgo biloba is characterized by rheological and blood-flow-promoting properties, protective effects against ischaemia and hypoxia, effects on nerve cell energy metabolism, antioedematous and myelin-protective effects, radical-scavenger activity, effects on various cerebral transmitter and receptor systems. These action principles constitute the rationale for clinical trials in vascular dementia and primary degenerative dementia of the Alzheimer type, and in mixed forms of both. The cerebral bioavailability of Ginkgo biloba extract has been demonstrated by electroencephalography. In clinical trials of different working-groups, effects of Ginkgo biloba on the cognitive performance, global function, and activities of the daily living have been found. Metaanalysis in the indication--demential disorders--comparing Ginkgo biloba versus acetylcholinesterase inhibitors have shown a similar clinical efficacy of both therapy regimens with an additional drug safety benefit for Ginkgo. Due to the clinical efficacy the WHO accepted Ginkgo biloba as an antidementiv drug and add it in January 2000 into the recent ATC-Classification Index. In future antidementive therapy drugs with an different mode of action should be given in combination. Furthermore clinical trials with fixed combinations of acetylcholinesterase inhibitors with Ginkgo biloba extracts in moderate or severe dementia would be necessary.

Post-marketing-surveillance studies with herbal drugs usually are prospective prescription-epidemiological studies, which should allow statements on quality, efficacy and safety. Until now neither laws nor concrete normative guidelines for the methodology and the evaluation of post-marketing-surveillance studies are existing which could be used for pharmacovigilance. In the present paper guidelines for planning, realisation and evaluation are presented which should allow studies of high quality. The essential components required for the investigational plan are focussed. Also recommendations on the obligatory, optional and special components of the study protocols are made. Additionally statistical methods which allow the evaluation of the therapeutic efficacy are presented.