trials. We conclude that electrodermal testing cannot diagnose allergy to common aeroallergens such as cat dander and house dust mite-allergens that have a strong association with atopic respiratory disorders such as asthma, rhinitis, eczema, and conjunctivitis.We thank Jackie Burnham for her help in preparing the manuscript, all the volunteers and the operators who gave up their time so willingly, and the doctors and practice manager at Hythe Medical Centre who made space and time available to us.Contributors: GTL, JNK, and STH conceived the study, developed the protocol, and obtained funding. JB was the trial manager. JG was responsible for the statistical design and randomisation, and PP for the analysis. All authors were jointly involved in writing the paper. STH will act as guarantor.Funding: The study was supported by funding from Vega Grieshaber, the Asthma Allergy and Inflammation Research Trust, and the Foundation for Integrated Medicine.Competing interests: GTL and JNK formerly had interests in a company involved in the distribution of Vega Grieshaber products and both have received fees for speaking at a seminar on the Vegatest. Results Improvement in the main variable was greater in the active group compared with placebo group (P < 0.001). Analysis of the secondary variables showed significant (P < 0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. Conclusions Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.

To investigate the hypothesis that early treatment of a migraine attack with sumatriptan, while pain is still mild, results in higher pain free rates in comparison to delayed treatment, when pain is at least moderate, we performed a prospective, controlled and open label study. Migraineurs with or without aura who fulfilled the diagnostic criteria recommended by the International Headache Society were enrolled in the study and randomly assigned to either 'early' or 'late' treatment with sumatriptan 100 mg tablets. In the early treatment group significantly more patients were pain free at all times measured during two hours after dosing than in the late treatment group. Furthermore, patients in the early treatment group became pain free significantly sooner after dosing than patients who delayed treatment. It is concluded that migraineurs, who are able to differentiate between a migraine attack and other forms of headache, benefit from early intervention with sumatriptan 100 mg tablets.

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Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa) have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo). Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic), assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients' self-assessments of general quality of life (QoL), responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65–19.35) score points, P < 0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55–11.39) score points, P = 0.0003 for 6.5 mg). QoL and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and QoL were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women.

A double-blind, randomized, placebo-controlled parallel-group trial (phase I) was performed to evaluate the central pharmacodynamic effects of two hypericum extracts with different contents of hyperforin (0.5% and 5.0%) but identical hypericin content. Three groups of 18 volunteers between 18 and 35 years of age participated in the trial. The volunteers receiving verum took 900 mg of the extract once a day for 8 consecutive days. The primary aim of this study was to observe the frequency bands, i.e., delta (1.25-4.5 Hz), theta (4.75-6.75 Hz), alpha-1 (7.0-9.5 Hz), alpha-2 (9.75-12.5 Hz), beta-1 (12.75-18.5 Hz), and beta-2 (18.75-35 Hz). This was the first study of its kind testing hypericum controlled on the basis of its hyperforin contents. A quantitative topographic EEG (qEEG) was performed on days 1 and 8 as an indicator of drug-induced pharmacological action. The volunteers' electrophysiological data were obtained prior to application and 2, 4, 6, 8, and 10 hours post administration. Plasma samples for evaluation of the pharmacokinetics of hyperforin were also obtained. The qEEG results of the placebo group on days 1 and 8 showed no significant changes with regard to their physiological daily rhythm. In both verum groups (0.5% and 5.0% hyperforin content), reproducible central pharmacodynamic effects were apparent in comparison to placebo, in particular with the extract containing 5.0% of hyperforin. A peak pharmacodynamic efficacy was observed between 4 and 8 hours post administration. These results were confirmed on day 8 of the trial. The extract containing 5.0% hyperforin showed a marked tendency to produce higher increases in qEEG baseline power performances than the one containing 0.5% hyperforin. These higher baseline outputs on day 8 were seen at the delta, theta, and alpha-1 frequency values. Compared to placebo there was a significant increase in qEEG power performance in the delta and beta-1 frequency values exclusively for the extract containing 5.0% hyperforin. The theta and alpha-1 frequency values showed a noticeable tendency more emphasized on day 8 than on day 1. Preclinical trials in rats have been observed with similar changes in the frequency bands mentioned above, especially in the cholinergic (delta), noradrenergic (theta) and serotonergic (alpha) neurotransmitter systems. These experimental findings suggest that hypericum extracts with a high hyperforin content have a shielding effect on the central nervous system.

The aim of this randomized, double-blind, placebo-controlled 16-week study was to investigate the clinical efficacy of cyclandelate (Natil®, 1,600 mg/day) in 139 adult outpatients with cognitive impairment (70 allocated to cyclandelate; 69 to placebo). Quantitative-topological EEG, event-related potentials (P300) and psychophysiological interview-based rating scales were used. The efficacy of cyclandelate was demonstrated in the confirmatory statistical sense using a global Hailperin-Rüger test on 10 predefined primary variables at global significance level of 0.05 relating to psychopathology, psychometry, neuropsychophysiology and behavior. At psychopathological and behavioral level the reduction of the total scores of the rating scales (Alzheimer Disease Assessment Scale, Sandoz Clinical Assessment Geriatric Scale, and Nürnberger Selbsteinschätzungs-Liste) following a 16-week therapy revealed also an individual significant cyclandelate-placebo distinction in the confirmatory statistical sense. A difference between verum and placebo was also observed by the increase of the number of correct answers during performance of the number symbol test (psychometrical level). The objective electrophysiological data (neuropsychophysiological level) support these findings. Of particular interest is that following cyclandelate treatment the absolute theta power remained almost unchanged and an increase of P300 amplitude was observed. At the same time placebo led to a distinct theta power increase and a decrease of P₃₀o amplitude, which was interpreted as the reflection of an impairment of the initial clinical state. Summarizing, cyclandelate proved to be efficacious compared to placebo in patients with mild to moderate cognitive impairment.

In a double-blind placebo-controlled psychopharmacological study 263 patients with cognitive impairment were screened and 137 of them were selected (following defined inclusion and exclusion criteria) to participate in a clinical trial (for results of treatment phase see part II, in preparation). The pretreatment state was evaluated twice using quantitative-topological EEG (qEEG) and psychopathological rating scales. There is a significant correlation between total score values of nearly all dementia-specific neuropsychological rating scales and absolute spectral power in the lower frequency ranges (delta, theta, alphas at rest. In order to increase the diagnostic power, qEEG was recorded simultaneously with the performance in four different psychometric tests. It was found that the worse the psychopathological rating of a patient, the higher the absolute theta power at rest and the smaller the test- and demand-dependent further increase in theta power. The percentage of task-induced power increase in delta and theta frequency range appeared to be an efficient indicator for a reliable discrimination between healthy elderly individuals and demented patients (rank correlation coefficient for theta in F7: r = +0.55), which will also serve for evaluation of treatment.

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