EEG maps of alcohol-dependent patients differ significantly from those of normal controls and patients suffering from other mental disorders and thus EEG mapping may be used for diagnostic purposes. Moreover, the quantitative EEG may also be of prognostic value as relapsing patients differ from abstaining ones, since they show a significantly more pronounced hyperarousal of the CNS.

Background: In 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine (AASM). Concerning the visual classification of sleep stages, these new rules are intended to replace the rules by Rechtschaffen and Kales (R&K). Methods: We adapted the automatic R&K sleep scoring system Somnolyzer 24 × 7 to comply with the AASM rules and subsequently performed a validation study based on 72 polysomnographies from the Siesta database (56 healthy subjects, 16 patients, 38 females, 34 males, aged 21–86 years). Scorings according to the AASM rules were performed manually by experienced sleep scorers and semi-automatically by the AASM version of the Somnolyzer. Manual scorings and Somnolyzer reviews were performed independently by at least 2 out of 8 experts from 4 sleep centers. Results: In the quality control process, sleep experts corrected 4.8 and 3.7% of the automatically assigned epochs, resulting in a reliability between 2 Somnolyzer-assisted scorings of 99% (Cohen’s kappa: 0.99). In contrast, the reliability between the 2 manual scorings was 82% (kappa: 0.76). The agreement between the 2 Somnolyzer-assisted and the 2 visual scorings was between 81% (kappa: 0.75) and 82% (kappa: 0.76). Conclusion: The AASM version of the Somnolyzer revealed an agreement between semi-automated and human expert scoring comparable to that published for the R&K version with a validity comparable to that of human experts, but with a reliability close to 1, thereby reducing interrater variability as well as scoring time to a minimum.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.

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s Abstract In a single-blind, placebo-controlled crossover trial, the acute efficacy of the dopamine agonist pramipexole was investigated in 11 restless legs syndrome (RLS) patients by sleep laboratory methods, with a clinical follow-up for 4 weeks. In 3 nights (pre-treatment, placebo and drug night), objective sleep quality was determined by polysomnography (PSG), subjective sleep and awakening quality by rating scales, objective awakening quality by psychometry. Clinical follow-up consisted of completion of the International RLS Study Group (IRLSSG) Scale, Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Concerning acute effects, an omnibus significance test for PSG variables demonstrated a global difference between placebo and pramipexole, but none between pre-treatment and placebo. Pramipexole 0.27 mg significantly decreased the target variable periodic leg movements (PLM)/h of sleep as well as all other RLS/PLM variables and improved objective sleep efficiency and subjective sleep quality as compared with placebo. In sleep architecture, sleep stages S1 and S2 and stage shifts increased, while slow-wave sleep and SREM decreased. After 4 weeks of therapy, the total scores of the IRLSSG questionnaire, sleep quality and daytime sleepiness, depression and quality of life also improved.Thus, acute pramipexole markedly reduced PLM measures and slightly improved objective and subjective sleep quality. Follow-up ratings showed a moderate improvement of RLS and sleep quality, and to a lesser extent of daytime sleepiness, depression and quality of life. The psychopathological findings as well as acute sleep architecture changes are reminiscent of those seen after activating antidepressants.s Key words restless legs syndrome · polysomnography · psychometry · sleep quality · pramipexole

Earlier investigations suggested an involvement of the right hemisphere and the left prefrontal cortex (PFC) in the pathogenesis of depression. This paper presents our own electroencephalographic (EEG) topography and low-resolution brain electromagnetic tomography (LORETA) data obtained in unmedicated depressed patients, and the effects of two representative drugs of non-sedative and sedative antidepressants, i.e., citalopram (CIT) and imipramine (IMI), as compared with placebo in normal subjects. Sixty female menopausal syndrome patients with the diagnosis of a depressive episode without psychotic symptoms as well as 30 healthy controls were investigated. Concerning the effects of antidepressants, normal healthy subjects received single oral doses of 20 mg CIT, 75 mg IMI and placebo p.o. A 3-min vigilance-controlled EEG and a 4-min resting EEG was recorded pre- and post-drug administration and analyzed by means of EEG mapping and LORETA. In the EEG mapping, depressed patients demonstrated a decrease in absolute power in all frequency bands, an augmentation of relative delta/theta and beta and a decrease in alpha activity as well as a slowing of the delta/theta centroid and an acceleration of the alpha and beta centroid, which suggests vigilance decrements. In the alpha asymmetry index, they showed right frontal hyper- and left frontal hypoactivation correlated with the Hamilton Depression Score (HAMD). LORETA predominantly revealed decreased power in the theta and alpha-1 frequency band. Negative correlations between theta power and the HAMD were observed in the ventro-medial PFC, the bilateral rostral anterior cingulate cortex (ACC) and the left insular cortex; between alpha-1 power and the HAMD in the right PFC. In the EEG mapping of antidepressants, 20 mg CIT showed mainly activating, 75 mg IMI partly sedative properties. LORETA revealed that CIT increased alpha-2, beta-1, beta-2 and beta-3 power more over the right than over the left hemisphere. However, also a left temporal and frontal delta increase was observed. In conclusion, EEG topography and tomography of depressed menopausal patients demonstrated a right frontal hyper- and left frontal hypoactivation in the alpha asymmetry index as well as a vigilance decrease, with a right-hemispheric preponderance. Within antidepressants at least 2 subtypes may be distinguished from the electrophysiological point of view, a non-sedative and a sedative. LORETA identifies cerebral generators responsible for the pathogenesis of depression as well as for the mode of action of antidepressants.

By multi-lead computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (QEEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping or topography), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ, the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects and therapeutic efficacy will be discussed. Imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be shown for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently. By considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. Thus, pharmaco-EEG topography and tomography are valuable methods in human neuropsychopharmacology, clinical psychiatry and neurology.

Objectives: Sleep bruxism (SB) is a parasomnia defined as a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. Pathophysiologically, SB is the result of biological and psychosocial influences. Treatment comprises behavioral, orthodontic and pharmacological interventions. While benzodiazepines and muscle relaxants have been reported by clinicians to reduce bruxism-related motor activity, placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate the acute effects of clonazepam (Rivotril^®) as compared with placebo, utilizing polysomnography and psychometry. Method: Ten drug-free outpatients (6 females, 4 males), aged 46.5 ± 13.1 years, suffering from SB (ICD-10: F45.8; ICSD: 306.8) and having been treated by bite splints were included in the trial. Comorbidity was high: 7 patients presented nonorganic insomnia related to adjustment or anxiety disorders (5 patients) or depression (2 patients); all patients had a concomitant movement disorder (6 restless legs syndrome, 4 periodic leg movement disorder). After one adaptation night, patients received placebo and 1 mg clonazepam 1/2 hour before lights out in a single-blind, nonrandomized study design. Objective sleep quality was determined by polysomnography, subjective sleep and awakening quality by rating scales, objective awakening quality by psychometric tests. Clinical evaluation was based on the Pittsburgh Sleep Quality Index (PSQI), the Zung Depression (SDS) and Anxiety (SAS) Scales, the Quality of Life Index, the Epworth Sleepiness Scale and the International Restless Legs Syndrome Study Group (IRLSSG) Scale. Results: On admission, SB patients exhibited deteriorated PSQI, SAS, SDS and IRLSSG measures. As compared with placebo, 1 mg clonazepam significantly improved the mean bruxism index from 9.3 to 6.3/h of sleep. Furthermore, it significantly improved the total sleep period, total sleep time, sleep efficiency, sleep latency and time awake during the total sleep period, and increased stage 2 sleep and movement time. Periodic leg movements decreased significantly, while the apnea index and apnea-hypopnea index increased marginally, but remained within normal limits. Subjective sleep quality improved as well, while in mood, performance and psychophysiology no changes were observed. Conclusion: Acute clonazepam therapy significantly improved not only the bruxism index but also objective and subjective sleep quality, with unchanged mood, performance and psychophysiological measures upon awakening, suggesting good tolerability of the drug.