[Сlinical and physiological characteristics and therapy asthenic disorders in adolescents girls]. / Kliniko-psikhofiziologicheskie osobennosti i terapiia astenicheskikh rasstroistv u devushek-podrostkov.

AIM: To study clinical and psychophysiological characteristics of asthenic disorders in adolescent girls in the aspect of treatment efficacy of cortexin. MATERIAL AND METHODS: Seventy-five women, aged 14-17 years, who were diagnosed with neurasthenia (ICD-10 F.48.0), were examined. Conventional neurological examination, a 10-point Visual Analogue Scale, the Multidimensional Fatigue Inventory (MFI-20), the A.M. Vein questionnaire, the Spielberger-Khanin questionnaire and EEG were used. RESULTS AND CONCLUSION: The high level of anxiety resulted in the development of autonomic symptoms and cephalgia. The EEG study showed that women with neurasthenia were characterized by lower alpha-rhythm power in the occipital sites compared with healthy peers. Treatment with cortexin improved patient's condition in 80% of cases that was supported by the positive EG dynamics.

Phenolic acids isolated from the fungus Schizophyllum commune exert analgesic activity by inhibiting voltage-gated sodium channels.

The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp. The analgesic activity of these compounds was tested in two types of mouse pain models induced by noxious chemicals. Five phenolic acids identified from SC extracts in the present study included vanillic acid, m-hydroxybenzoic acid, o-hydroxybenzeneacetic acid, 3-hydroxy-5-methybenzoic acid, and p-hydroxybenzoic acid. They inhibited the activity of both tetrodotoxin-resistant (TTX-r) and tetrodotoxin-sensitive (TTX-s) NaV channels. All the compounds showed low selectivity on NaV channel subtypes. After intraperitoneal injection, three compounds of these compounds exerted analgesic activity in mice. In conclusion, phenolic acids identified in SC demonstrated analgesic activity, facilitating the mechanistic studies of SC in the treatment of neurasthenia.

[Asthenic disorders in children and their differentiated treatment].

OBJECTIVE: To study clinical/psychological characteristics of neurasthenia and residual asthenia and to assess the efficacy of noofen and adaptol in the treatment of these disorders. MATERIAL AND METHODS: Authors examined 30 adolescents with neurasthenia and 30 with residual asthenia. The Multidimensional Fatigue Inventory (MFI-20), A.M. Vein questionnaire, Spilberger-Khanin questionnaire, The Test of Variables of Attention (TOVA) were used. Patients were divided into two equal groups (n=30), each included 15 patients with residual asthenia and neurasthenia. Patients of the first group received adaptol in dosage 1000 mg daily and patients of the second group received noofen in dosage 500 mg daily. The duration of the study was 30 days. RESULTS AND CONCLUSION: The significantly higher levels of fatigue, inattention and exhaustibility were identified in patients with residual asthenia. Adolescents with neurasthenia were characterized by higher anxiety. The higher efficacy of adaptol in treatment of neurasthenia (80% in adolescents with neurasthenia and 60% of patients with residual asthenia) was shown. Noofen was more effective in treatment of residual asthenia (66.7% of adolescents with neurasthenia and 86.7% with residual asthenia.

[Treatment of asthenic syndrome in patients with chronic brain ischemia: results of the non-interventional observational program TRIUMPH].

OBJECTIVE: To assess the severity of asthenic syndrome (AS) in chronic brain ischemia (CBI) in primary health care settings. MATERIAL AND METHODS: The study included 1170 patients with brain ischemia, aged 45-65 years, treated with phenotropil in dose 100 mg during 2 and 3 months. Clinical examination and MFI-20 subscales were administered. RESULTS AND СONCLUSION: The high incidence of asthenic syndrome was observed across all MFI-20 subscales. The decrease in asthenic syndrome severity was significant already in the end of the first month of treatment with phenotropil. Such dynamics maintained to the end of the second and third month of treatment. More than 2-fold decrease in the severity of asthenia symptoms was achieved in all subgroups 3 months after treatment. More rapid and apparent decrease in asthenic syndrome was observed in younger patients.

[Ladasten versus placebo effect self-evaluated by neurasthenia patients with different EEG alpha rhythm types].

The study was focused on the clinico-pharmacological analysis of differences between subjective and objective assessment of the effects of antiasthenic drug ladasten and placebo effects in patients with neurasthenia with different individual patterns manifested in their EEG alpha rhythms and MMPI findings. It is established that, in patients with neurasthenia characterized by reduced EEG alpha activity combined with emotional lability and inertness, the therapeutic action and effectiveness of ladasten and placebo was more robust (the subjective estimation was higher) than in patients with prominent alpha rhythm and sthenic personal traits. The self-assessment of the effect of single test doses of ladasten and placebo was independent of the individual differences of EEG alpha rhythm organization and personal traits with respect to tolerability, wish to continue the treatment, activating and calming effects. In long-term treatment, higher subjective estimations of the ladasten and placebo effect appeared in patients with reduced EEG alpha rhythm, and the difference corresponded to objective indices of the psychotropic action and effectiveness of the drug.

Phase II trial on the effects of Silexan in patients with neurasthenia, post-traumatic stress disorder or somatization disorder.

Silexan, a novel lavender oil preparation for oral use, has been authorized in Germany for the treatment of states of restlessness during anxious mood. An open-label, exploratory trial was performed to assess the potential of the medicinal product in the treatment of restlessness caused by anxiety as related to several disorders. Outcome measures included the Symptom Checklist-90-Revised (SCL-90-R), von Zerssen's Depression Scale (D-S), the 36-item Short Form Health Survey Questionnaire (SF-36), and a sleep diary. 50 male and female patients with neurasthenia (ICD-10 F48.0), post-traumatic stress disorder (PSD; F43.1), or somatization disorder (F45.0, F45.1) were included to receive 1 × 80 mg/day Silexan over 6 weeks; 47 could be analyzed for efficacy as full analysis set. At baseline, patients suffered from restlessness (96%), depressed mood (98%), sleep disturbances (92%), or anxiety (72%). Of those, resp. 62%, resp. 57%, resp.51%, resp. 62% showed improvements during treatment (p < 0.001). For all patients, mean D-S score decreased by 32.7% and SCL-90-R Global Severity Index by 36.4% as compared to baseline, (p < 0.001), while the SF-36 Mental Health Score increased by 48.2% (p < 0.001). Waking-up frequency (p = 0.002), Waking-up duration (p < 0.001) and morning tiredness (p = 0.005) were reduced, while efficiency of sleep (p = 0.018) and mood (p = 0.03) improved. Patients suffering from neurasthenia or PSD showed comparable improvements with most outcomes. The results in this trial justify to further investigate Silexan in disorders with accompanying restlessness caused by sub-threshold anxiety. Adverse reactions, predominantly gastrointestinal complaints, were judged as mild or moderate.

[Self-evaluation of single test doses and objective indices of ladasten vs. placebo efficacy in neurasthenic patients].

Self-evaluation of the effect of single-dose (15 mg) ladasten administration versus placebo has been studied in patients with neurasthenia diagnosis. Relationships between self-evaluation parameters and personal features, psychopathological and psychophysiological parameters of patients, drug action characteristics, and course treatment effectiveness have been analyzed. Results suggest that the self-rated high tolerability of ladasten treatment is comparable with that of placebo. No relationships are found between the self-evaluated single-dose effects of ladasten and personal features of patients. Correlations of the self-estimations and some psychopathological and psychophysiological parameters before treatment, main drug effects, and overall course treatment effectiveness are revealed, whereas the self-evaluation of placebo effect was related to personal features.

[Asthenic disorders in children].

The present study comprised two parts. In the first part, authors attempted to work out the systematics of asthenic disorders based on our own observations of 189 children aged 7-14 years. The following clinical variants of asthenic states in children were singled out: cerebrogenic asthenia (14.3%), somatogenic (13.8%), residual (16.4%), dysontogenetic (20.1%) and neurasthenia (35.4%). In the second part, we summarized the results of treatment of neurasthenia with adaptol (32 patients) compared to pantoham (30 patients). The efficacy of adaptol was higher: the improvement was seen in 71.9% of cases compared to pantoham (56.7%). The good tolerability of adaptol which clinical efficacy is confirmed by neurophysiological and psychological studies is discussed.

[Ladasten, the new drug with psychostimulant and anxiolytic actions in treatment of neurasthenia (results of the comparative clinical study with placebo)].

An aim of a randomized blind study was to assess therapeutic efficacy and safety of ladasten used as an antiastenic drug in patients with neurasthenia. Tasks of the study included the investigation of characteristics of therapeutical actions, efficacy of the drug comparing to placebo, possible side-effects and probability of the development of "withdrawal syndromes". The design of the study included a wash-out period, a monotherapy with ladasten and placebo during 28 days and a final 1-week period of receiving placebo. Standartisized objective and subjective methods of mental state evaluation in patients were administered. The results obtained suggest that a combination of psychostimulant and anxiolytic actions in the spectrum of psychotropic activity of ladasten determines the its high therapeutic efficacy in asthenic disorders. It has been found that ladasten is superior in the rate and degree of reduction of main symptoms of asthenic syndrome compared to placebo. The absence of "withdrawal syndrome" after the drug withdrawal reveals the lack of addictive potential in this drug.

[Characteristics of ladasten effect in neurasthenia patients with various EEG parameters].

Clinical and electroencephalographic (EEG) analysis ofladasten action in anxiety-asthenic patients with respect to their EEG-defined individual typological characteristics was carried out. Primary psychopathologic disorders and ladasten effects were assessed by objective classification methods (factor and cluster analyses), and individual EEG types characterized by marked or reduced alpha rhythm were determined. No significant correlations between baseline EEG results and the initial mental condition indices were found. Significant differences ofladasten action in patients with different EEG types were found. It was established that, in patients with marked alpha rhythm corresponding to asthenic personal traits, ladasten exhibits predominantly a psychostimulant action assessed by clinical rating scales, which is accompanied by high frequencies of alpha rhythm increase and beta 1 and beta 2 rhythms decrease. In patients with reduced alpha rhythm and the EEG type corresponding to asthenic personal traits, ladasten action was characterized by an increase of alpha-rhythm low frequencies and the opposite reaction of beta 1 and beta 2 rhythms, whose are typical for the EEG pattern of anxiolytic effect. These results may indicate that the effect of ladasten depends on the initial brain activity level, which varies in patients with different individual typological traits.

[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia].

Sixty-two patients with generalized anxiety disorder (GAD) and neurasthenia were studied. The effect of selank (30 patients) was compared to that of medazepam (32 patients). Patient's state was assessed with psychometric scales (Hamilton, Zung, CGI). Enkephalin activity in the blood serum was measured as well. The anxiolytic effects of both drugs were similar but selank had also antiasthenic and psychostimulant effects. The clinical-biological study revealed that patients with GAD and neurasthenia had the decreased level of tau(1/2) leu-enkephalin which was correlated with disease duration, severity of symptoms related to anxiety and asthenia and autonomic disorders. The increase of this parameter and stronger positive correlations with anxiety level were observed during the treatment with selank mostly in patients with GAD.

Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial.

BACKGROUND: Single interventions in chronic fatigue syndrome have shown only limited effectiveness, with few studies of comprehensive treatment programmes. AIMS: To examine the effect of a comprehensive cognitive-behavioural treatment (CCBT) programme compared with placebo-controlled mirtazapine medication in patients with chronic fatigue, and to study the effect of combined medication and CCBT. METHOD: A three-armed randomised clinical trial of mirtazapine, placebo and a CCBT programme was conducted to investigate treatment effect in a patient group (n=72) with chronic fatigue referred to a specialist clinic. The CCBT programme was compared with mirtazapine or placebo therapy for 12 weeks, followed by 12 weeks treatment with a mixed crossover-combination design. Assessments were done at 12 weeks and 24 weeks. RESULTS: By 12 weeks the treatment effect was significantly better in the group initially receiving CCBT, as assessed with the Fatigue Scale (P=0.014) and the Clinical Global Impression Scale (P=0.001). By 24 weeks the treatment group initially receiving CCBT for 12 weeks followed by mirtazapine for 12 weeks showed significant improvement compared with the other treatment groups on the Fatigue Scale (P<0.001) and the Clinical Global Impression Scale (P=0.002). Secondary outcome measures showed overall improvement with no significant difference between treatment groups. CONCLUSIONS: Multimodal interventions may have positive treatment effects in chronic fatigue syndrome. Sequence of interventions seem to be of importance.

A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neurasthenia.

Ganoderma lucidum has been widely used to treat various diseases, including cancer, diabetes, and neurasthenia in many Asian countries. This randomized, double-blind, placebo-controlled parallel study aimed to investigate the efficacy and safety of a polysaccharide extract of G. lucidum (Ganopoly) in Chinese patients with neurasthenia. One hundred thirty-two patients with neurasthenia according to the diagnosis criteria of the 10th International Classification of Diseases were included in this study. Written consents were obtained from the patients, and the study was conducted in accordance with Good Clinical Practice guidelines. Patients were randomized to receive Ganopoly or placebo orally at 1,800 mg three times a day for 8 weeks. Efficacy assessments comprised the Clinical Global Impression (CGI) improvement of severity scale and the Visual Analogues Scales for the sense of fatigue and well-being. In 123 assessable patients in two treatment groups at the end of the study, Ganopoly treatment for 8 weeks resulted in significantly lower scores after 8 weeks in the CGI severity score and sense of fatigue, with a respective reduction of 15.5% and 28.3% from baseline, whereas the reductions in the placebo group were 4.9% and 20.1%, respectively. The score at day 56 in the sense of well-being increased from baseline to 38.7% in the Ganopoly group compared with 29.7% in the placebo group. The distribution of the five possible outcomes from very much improved to minimally worse was significantly different (X (2) = 10.55; df = 4; P = .0322) after treatment with Ganopoly or placebo. There was a percentage of 51.6% (32 of 62) in the Ganopoly group rated as more than minimally improved compared with 24.6% (15 of 61) in the placebo group (X (2) = 9.51; df = 1; P = .002). Ganopoly was well tolerated in the study patients. These findings indicated that Ganopoly was significantly superior to placebo with respect to the clinical improvement of symptoms in neurasthenia.

[Atypical depression and related illnesses--neurobiological principles for their treatment with Hypericum extract]. / Die atypische Depression und verwandte Erkrankungen-Neurobiologische Grundlagen für ihre Behandlung mit Johanniskraut-Extrakt.

Atypical depression, somatoform disorder, neurasthenia and fibromyalgia seem to form a spectrum of disorders, who share a common biological basis, i.e. a reduced activity of the hypothalamus-pituitary-adrenocortical (HPA)-system. This is similar to the situation in Cushing's disease, where the central part of the hypothalamus-pituitary-adrenocortical-system is decreased by an increased feedback via increased intracerebral cortisol concentration. Cushing's disease is accompanied by features of atypical depression and of somatisation. Treatment with hypericum seems to disinhibit the hypothalamus-pituitary-adrenocortical-system in healthy subjects and patients with a depression. Furthermore it decreases intracerebral corticosteroids, possibly by increasing the expression of p-glycoprotein at the blood brain barrier. Therefore hypericum might be especially effective in patients with a symptom cluster of atypical depressive features and somatisation. Clinical studies with patients with depression with atypical features like the seasonal affective disorder (SAD) and with patients with a depressive syndrome accompanied by somatic complaints or fatigue support this view.

[Clinical study of the selective anxiolytic agent afobazol]. / Rezul'taty klinicheskogo izucheniia selektivnogo anksiolitika afobazola.

A standard clinical trial including pharmaco-EEG investigation of the new selective anxiolytic afobazole was performed on a group of 30 patients with anxiety and anxious-asthenic disorders and premorbid individual asthenic profile traits. Afobazole exhibits the anxiolytic action with an activating component in the absence of sedative and myorelaxant effects. The clinical trial results confirmed good prospects of using the experimentally validated pharmacogenetic concept of anxioselectivity as a methodological approach to the design of new drugs possessing selective anxiolytic properties.

[Neurasthenia as a variant of the asthenic syndrome: a pharmacotherapeutic analysis modelled on tanakan therapy]. / Nevrasteniia kak variant astenicheskogo sindroma: farmakoterapevticheskii analiz na modeli terapii tanakanom.

25 patients with neurasthenia were examined during 2 months of ambulatory therapy with tanakan. Taking into consideration the data of cluster analysis of symptomatology before the therapy, 2 groups of patients were selected: with hyposthenic (15 patients) and hypersthenic (10 patients) variations of the disease. The main symptom complex in both groups was an asthenic one, but symptomatology in group 1 tended to hyporeactivity and depressive range of affective spectrum, while in group 2--to hyperreactivity, hyperesthesia, irritation, anxious range of disorders. Pronounced improvement was observed in 18 cases, moderate effect--in 4 patients; in 3 cases the treatment was discontinued because of side-effects (headache, allergic reactions, etc). In group 1 efficiency of the treatment was higher and stable positive dynamics of the state was found, while in group 2 there was uneven reduction of the symptoms with partial temporary change (the exacerbation of anxious symptoms). The data obtained support correctness of the division of neurasthenia into hyposthenic and hypersthenic variations and expediency of taking into consideration such differences in therapeutic policy.

[Therapy of cardio-neurotic diseases in general practice: clinical experience with atarax]. / Terapiia kardionevroticheskikh rasstroist v obshcheterapevticheskoi praktike: opyt primeneniia ataraksa.

An open study of efficiency and safety of atarax (hydroxisine) enrolled 55 outpatients (23 males and 32 females, mean age 45.91 +/- 1.91) with generalized anxious and somatoform disorders running as cardioneurosis as well as nosogenic reactions (maladaptation), manifestations of cardiovascular pathology (acute myocardial infarction, angina of effort functional class II-III, postinfarction cardiosclerosis, essential hypertension in 5, 13, 2 and 5 patients, respectively). The patients received atarax for 28 days (daily dose 50 mg). The course was completed in 54 patients. In 47 of them, the overall score value by Hamilton Anxiety Scale dropped by 10 scores, the reduction being more obvious in patients with somatic anxiety. Hydroxysine is well tolerated and safe both in patients with somatic pathology and those with cardiovascular disorders.