The aim of the study was to demonstrate competition between caffeine and a fixed valerian/hop extract combination (Ze91019) by the central adenosine mechanism. EEG was used to describe the action of caffeine on the central nervous system after oral administration (200 mg) in healthy volunteers. In addition to caffeine, the volunteers (16 in each group) received either placebo or verum (2 and 6 tablets containing the valerian/hop extract). The EEG responses were recorded every 30 min thereafter. The verum medication was capable of reducing (2 tablets) or inhibiting (6 tablets) the arousal induced by caffeine. This pharmacodynamic action was observed 60 minutes after oral administration, indicating not only competition between the antagonist caffeine and the partial agonist, i. e., the valerian/hop extract but also bio-availability of the compound(s) responsible for the agonistic action. In conclusion, the valerian/hop extract acts via a central adenosine mechanism which is possibly the reason for its sleep-inducing and -maintaining activity.

In the present study, the attempt has been made to evaluate, under ward conditions, the special emotional dynamics involved of a highly alexithymic man with persistent somatoform pain disorder, and to put these dynamics in connection with the recorded autonomous regulation events then. As results, 1. an elevated tonus of the sympathetic system was recorded, which 2. showed a visible dynamics within the therapeutic process, connected with a lowering of the sympathetic tonus and a better stress management. 3. The change of therapists led to a deterioration (week 6, absence of therapist) vs. a recovery (week 8, return of therapist) of the vegetative activity. 4. This improvement in the ability for physiological peripheral regulation was accompanied by a reduction of the headache intensity. 5. The headaches, assessed subjectively, stabilized at the end of the treatment in comparison with the beginning of treatment on a lower level. Although it is not permitted to transfer the results of this individual case study to other patients with somatoform disorder. To this controlled studies are required at larger patient collectives. However, this study provides first notes for an influence of the autonomous functions of a psychodynamic psychotherapy in the field of persistent pain disorders and possible connections with the emotional dynamics as well as with the leading symptomatology can be recognized.

Das prämenstruelle Syndrom ist eine komplexe Kombination aus psychologischen Symptomen wie Reizbarkeit, aggressivem Verhalten, Anspannungen, Angstgefühlen, depressiven Gedanken, aber auch aus körperlichen Beschwerden wie dem Gefühl des Aufgeblähtseins, Anspannungen in den Brüsten und krampfartigen Schmerzen. Diese Beschwerden treten unberücksichtigt eventueller sozioökonomischer Faktoren auf. Die Ursachen des prämenstruellen Syndroms sind noch nicht sicher bekannt [10]. Veränderungen auf der hormonellen Ebene, aber auch auf der Ebene verschiedener Neurotransmitter und des Prostaglandinstoffwechsels werden diskutiert [6].

OBJECTIVES:To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome.DESIGN:Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles.SETTING:General medicine community clinics.PARTICIPANTS:178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days.INTERVENTIONS:Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles.MAIN OUTCOME MEASURES:Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms).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.

This clinical trial was designed to evaluate the efficacy of the external nasal dilator Breathe Right (nasal strip) on snoring. The assessment of snoring intensity and duration as well as the sleep quality without the Breathe Right nasal strip and after application was performed in 30 out-patients with primary habitual snoring. An all-night polysomnographic investigation including registration of a17-channel EEG, EMG, respiration parameters such as breathing efforts and nasal/oral air flow, snoring vibrations, ECG, oxygen saturation, etc. was conducted in the sleep laboratory of Pro Science Private Research Clinic GmbH. The drug-free strip Breathe Right was able to reduce the maximum snoring intensity (maximum snoring vibration) throughout the night (p = 0.02, sign test), especially during the superficial sleep (sleep stage 1 and 2). The snoring intensity remained almost unchanged during slow wave sleep (SWS) and REM. In comparison with the baseline the maximum snoring intensity was reduced during the second treatment night in 22 of the 30 investigated snorers. The differentiation between snorers with and without obstructive sleep apnea and between mild and heavy snorers allowed to state that especially the snorers without apnea and the time in bed, TIB) can achieve a reduction of the maximum snoring intensity using the strip. Moreover, the number of snores per hour TIB (snoring index, SI) was reduced after application of the nasal strip for the snores with an intensity greater than 20 dB (p = 0.02, sign test). The sleep architecture remained almost unchanged, although the nasal strip led subjectively (SF-A questionnaire) to an improvement of sleep quality. The overall estimation of the subjective efficacy rating revealed that 17 of 30 patients (second treatment night) needed a certain period of time to accustom to the nasal strip. After that they could breathe easily, slept well and felt recuperated in the following morning. No adverse events were observed after adhesion of the nasal strip, except for one patient, who had the sensation as if they needed to sneeze for a short time after the first application of the nasal strip. Consequently, Breathe Right is a safe and easily applied noninvasive method to reduce the maximum snoring intensity, especially in habitual mild snorers.

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.

After a 4 months randomized double-blind study with cyclandelate versus propranolol ail patients kept a miniaturized headache diary for one more year. Both duration of migraine attacks in hours and the number of additional analgetic medication were recorded monthly. Reduction of the duration of migraine attacks in the clinical responders of the cyclandelate treated patients remained nearly unchanged. In the propranolol responders the duration of migraine attacks in hours increased from the third month after finishing the medication and reached values comparable to those at the beginning of the active treatment. Intake of additional analgetic medication during the 1-year-follow-up was tower in the cyclandelate responders than in the propranolol-responders. Cyclandelate can be described as an effective long-lasting drug in migraine prophylaxis.

A highly sensitive quantitative-topographical EEG was used in order to define first steps in an objective classification of migraine. A 17-channel quantitative EEG was recorded in 30 patients suffering from migraine with or without aura during the painfree interval. These EEG s were compared to EEGs of age related healthy norm groups using a new statistical tool called the Aberration Index. A focal aberration in the area of pain was detected in 26 out of the 30 patients mostly due to an increase of alpha1 EEG power (23 patients). Alpha2 or theta power were also increased in several patients. Furthermore, a decrease in alpha power neighbouring the focus was found in 18 patients and a contralateral reduction of alpha power was seen in 16 patients. No difference was detected between migraine with aura and migraine without aura.

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 P300 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.

Electrical changes of the brain induced by mental work in the presence or absence of a drug formulation containing dimethylaminoethanolorotrate (DMAE), vitamins and minerals were analysed. Sixty elderly volunteers (30 females and 30 males; aged 40 - 65) who lacked concentration and efficiency during mental exercise according to their own opinions participated in a double-blind, placebo-controlled study. The EEG recordings were carried out before and after 12 weeks medication and were analysed according to the electrical charges at the scalp surface (Laplacian estimate) followed by Fast Fourier Transformation to obtain quantitative data. Whereas no change of electrical charge could be observed after 12 weeks of treatment in the placebo group, the verum group taking 1 capsule per day of an established drug containing a biogenic amine-vitamin combination revealed decreases in theta power during rest and increases in absolute theta power induced by mental demand within the area known to change its electrical activity during mental exercise. In the light of the current hypothesis that high theta resting power and low increases at frontotemporal brain areas during mental work indicate mental impairment, treatment with the drug under investigation was seen to successfully reverse these changes. This drug effect was localized in the frontotemporal cortex in a statistically significant manner during both the memory and the symbol recognition tests. The observed effect is fully consistent with a previous study using Fourier transformed data from conventional EEG voltage recordings. It can be concluded that an analysis of EEG data by means of the charge mode provides an excellent tool to quantify drug effects especially in cognitive research. A second perspective arises from the fact that it should be possible to recognize mental impairments at a very early stage by using this method, thus providing the possibility of an early treatment.

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, alpha 1) 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.

The aim of this study was to investigate the activation process of the central nervous system during mental demand in a complex psychophysiological situation. A 17-channel quantitative topographical EEG was recorded in 48 healthy volunteers (male and female, aged 49 +/- 6 years), using the CATEEM system, during four different psychometric tests (simple reaction time measurement, concentration performance, figure detection and word recall test). The mental load varied with each test, producing a graduated increase in spectral power density in delta and theta frequency range on the EEG in the fronto-temporal, parietal and occipital regions of the cortex and a generalized decrease in alpha power. During the rest periods after each test a graduated increase in alpha 1 power was seen as a possible expression of change in vigilance level. With this method we were able to differentiate two effects of psychometric tests on brain activity: the actual mental demand itself and the influence on the vigilance level.

Approximately one-third of schizophrenic patients receiving antipsychotic drugs obtain little or no benefit from them. In some reports, response has been linked with "prognostic" factors, including abnormal EEG and drug response (pharmaco-EEG). Measurements of topological EEG spectral power and Brief Psychiatric Rating Scale (BPRS) values were obtained in 15 schizophrenics over a period of 20 min immediately after the first application, and at weekly intervals after single intramuscular injection of 2 ml depot haloperidol (Haldol-Decanoate). A highly significant increase in the alpha-1 power density at almost all positions and an increase in theta power at parietotemporal regions can be described as electrophysiological parameters of the acute pharmaco-EEG. BPRS values decreased continuously within the first 2 weeks followed by an increase to the predrug level after the fourth week. Over the whole observation period there was a correlation between neurophysiological data (alpha-1 power) and clinical symptomatology (BPRS total score; r = -0.7). Therefore, it can be concluded that quantitative EEG recordings are able to serve as a tool for the optimization of the depot neuroleptic treatment in schizophrenics.

Assessment of the Mental Performance during Simultaneous Quantitative Topographical Electroencephalometry and Psychometry in Pharmacology/Proof of influence of a biogenic amine-vitamin combination. The aim of this study was to verify the effect of a combination medicine (Vita-Gerin-Geistlich) on the human EEG pattern during psychometric (cognitive) tests given to 43 patients with poor concentration and thinking problems. A randomised, parallel, placebo-controlled double-blind study was performed. Applying 17-channel quantitative electroencephalometry and psychometric tests simultaneously this study revealed a test-dependent increase in absolute spectral EEG power in the delta and theta frequency bands, mainly observed in the frontotemporal cortex. After 8 weeks the increase in EEG power differed significantly with respect to taking placebo and verum (1 capsule/day). Verum caused a stronger rise in spectral delta and theta power, the psychometric test performance also improved. Both effects could be verified statistically. The novel EEG-controlled psychometric test set (enabling artefact-free EEG recording during psychometric tests) which was developed and used in this study represents a valid tool for future pharmacological research.