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Anxiety and depressive disorders have overlapping symptoms and share common neurobiological pathways. Antidepressant drugs have been demonstrated to be efficacious in anxiety as well. Vice versa, it may also be promising to investigate the efficacy of anxiolytic drugs such as silexan in major depressive disorder (MDD). Patients with a mild or moderate, single or recurrent episode of MDD and a total score of 19-34 points on the Montgomery Åsberg Depression Rating Scale (MADRS) were randomized to receive 1 × 80 mg/d silexan, 1 × 50 mg/d sertraline, or placebo double-blind, double-dummy for 56 days. The primary outcome measure was the MADRS total score change between baseline and treatment end. Treatment groups were compared using a treatment policy estimand. 498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan and sertraline were superior to placebo for MADRS total score reduction, with absolute differences to placebo of 2.17 (95% confidence interval: 0.58; 3.76) points and 2.59 (1.02; 4.17) points, respectively (p < 0.01). Moreover, silexan was superior to placebo for alleviation of functional impairment according to the Sheehan Disability Scale with a difference of 2.40 (1.04; 3.76) points (p < 0.001). Both treatments were well tolerated; eructation was the most frequent adverse effect of silexan. The study confirms the antidepressant efficacy of silexan in mild or moderate MDD, including significant improvements in the subjects' functional capacity. The results for sertraline confirm the assay sensitivity of the trial. Both drugs were well tolerated.Trial registrationEudraCT2020-000688-22 first entered on 12/08/2020.
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INTRODUCTION: We report on a meta-analysis of Silexan, a proprietary active substance produced from Lavandula angustifolia, in subthreshold anxiety, mixed anxiety and depressive disorder (MADD), and generalized anxiety disorder (GAD). METHODS: The present analyses are based on all currently completed 5 double-blind, randomized, placebo-controlled trials investigating Silexan in adult out-patients who received Silexan 1 × 80 mg/day or placebo for ten weeks according to random assignment (n = 1213). Efficacy was assessed based on the Hamilton Anxiety Rating Scale (HAMA), several anxiety self-rating scales, the Clinical Global Impression (CGI) scale, and the Short Form-36 (SF-36) health status questionnaire. RESULTS: After ten weeks' treatment, Silexan was significantly superior to placebo in reducing the HAMA total score (including the psychic and somatic anxiety sub-scores) and self-rated anxiety. Based on a ≥ 50% HAMA total score reduction, the responder rate ratio was 1.34 favoring Silexan, and the rate ratio of subjects much or very much improved according to the CGI was 1.51. Silexan was also significantly superior in improving the physical and mental health summary scores of the SF-36. There were no significant between-group differences concerning the occurrence of adverse events (AEs), serious AEs, and premature withdrawal due to AEs. CONCLUSIONS: This meta-analysis demonstrates that Silexan exerts significant anxiolytic effects in subthreshold anxiety, GAD and MADD that were consistently reflected in investigator ratings and patient-reported outcomes, including improvement of health-related life-quality, while showing favorable tolerability and safety.
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Ansiolíticos , Lavandula , Óleos Voláteis , Adulto , Humanos , Óleos de Plantas , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/induzido quimicamente , Ansiolíticos/efeitos adversos , Método Duplo-Cego , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Silexan is a proprietary active substance produced from Lavandula angustifolia, with proven anxiolytic efficacy in subthreshold and generalized anxiety disorder as well as in mixed anxiety and depressive disorder with beneficial impact on anxiety-related sleep disturbances. The pharmacological profile and clinical observations suggest that Silexan may also have an antidepressant effect. To investigate the effect of Silexan on co-occurring depressive symptoms, we present a meta-analysis of the five placebo-controlled clinical trials hitherto performed with Silexan in subthreshold anxiety (n = 3) and anxiety disorders (n = 2). Patients of all trials received Silexan 1 × 80 mg/day or placebo for 10 weeks according to random assignment. Assessment of the antidepressant effect was based on item 'depressed mood' from the Hamilton Anxiety Rating Scale (HAMA) administered in all trials and on the total scores of the Montgomery Åsberg Depression Rating Scale (MADRS) or the Hamilton Depression Rating Scale (HAMD) used in three trials. After 10-week treatment, patients receiving Silexan showed significantly more pronounced score reduction for HAMA item 'depressed mood' than those in the placebo group (p = 0.01). Significant superiority of Silexan over placebo could also be shown for mean MADRS or HAMD total score reduction (three studies; p < 0.01). Silexan-treated patients with more severe depressive symptoms at baseline showed more pronounced improvements than those with milder symptoms. Our meta-analysis clearly shows that Silexan has a beneficial effect on co-occurring depressive symptoms in patients with subthreshold anxiety and anxiety disorders and may, hence, lead to important therapeutic implications for depressive disorders.
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Transtornos de Ansiedade , Depressão , Humanos , Depressão/tratamento farmacológico , Transtornos de Ansiedade/tratamento farmacológico , Ansiedade/tratamento farmacológico , Antidepressivos/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Quantifying depression mainly relies on the use of depression scales, and understanding their factor structure is crucial for evaluating their validity. METHODS: This post-hoc analysis utilized prospectively collected data from a naturalistic study of 1014 inpatients with major depression. Confirmatory and exploratory factor analyses were performed to test the psychometric abilities of the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the self-rated Beck Depression Inventory. A combined factor analysis was also conducted including all items of all scales. RESULTS: All three scales showed good to very good internal consistency. The HAMD-17 had four factors: an "anxiety" factor, a "depression" factor, an "insomnia" factor, and a "somatic" factor. The MADRS also had four factors: a "sadness" factor, a neurovegetative factor, a "detachment" factor and a "negative thoughts" factor, while the BDI had three factors: a "negative attitude towards self" factor, a "performance impairment" factor, and a "somatic" factor. The combined factor analysis suggested that self-ratings might reflect a distinct illness dimension within major depression. CONCLUSIONS: The factors obtained in this study are comparable to those found in previous research. Self and clinician ratings are complementary and not redundant, highlighting the importance of using multiple measures to quantify depression.
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Transtorno Depressivo Maior , Pacientes Internados , Humanos , Reprodutibilidade dos Testes , Transtorno Depressivo Maior/diagnóstico , Ansiedade , Transtornos de Ansiedade , Escalas de Graduação Psiquiátrica , PsicometriaRESUMO
Hanns Hippius (1925-2021) can be seen as a stimulating pioneer of Psychopharmacology and of Neuroscience. He was very influential in this area not only in Germany, but also on an international level. With reference to clinical psychopharmacology especially his activities for the development of Clozapine are of greatest importance. When he became Chairman of the Psychiatric Department of the Ludwig-Maximilians-University Munich (1971-1994), he established all necessary facilities for research in Psychopharmacology and Neuroscience, which was at that time a great progress in psychiatry. This was the base to establish a Munich school of clinical psychopharmacology and neuroscience. A majority of his co-workers did research in psychopharmacology and neuroscience and made their academic careers in this area and several achieved university chair positions in Germany, on which they could procreate the standards and knowledge of the Munich school of psychopharmacology and neuroscience. His engagement for psychopharmacology can be seen in addition in the fact that he was co-founder and one of the first presidents of CINP (1972-1974), the International College of Psychopharmacology. The recollections presented in this article describe the objective data as well as some personal experiences of the author.
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Psiquiatria , Psicofarmacologia , Humanos , Alemanha , Instituições AcadêmicasRESUMO
PURPOSE: In diagnostic systems (e.g., DSM-5, ICD-10), depression is defined categorically. However, the concept of subthreshold depression (SD) has gained increasing interest in recent years. The purpose of the present paper was to review, based on a scoping review, the relevant papers in this field published between October 2011 and September 2020. MATERIALS AND METHODS: Of the 1,160 papers identified, 64 records could be included in further analysis. The scoping review was conducted using both electronic and manual methods. RESULTS: The main result of the analysis is that the operationalisation criteria used are highly heterogeneous, which also leads to very heterogenous epidemiological data. CONCLUSIONS: Clear conclusions are not possible scrutinising the reported results. Most definitions seem to be arbitrary, with considerable overlap (e.g., between SD and minor depression). The review also revealed that the impact of SD on quality of life and related parameters appear to be in the range of the respective impact of major depression (MD) and therapeutic approaches might be helpful for SD and also for the prevention of conversion from SD to MD. Keeping the presented difficulties in mind, a proposal for the definition of SD is made in the present paper in order to facilitate the discussion leading to more homogeneous criteria.
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Depressão , Transtorno Depressivo Maior , Humanos , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/tratamento farmacológico , Qualidade de Vida , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/tratamento farmacológico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Classificação Internacional de DoençasRESUMO
Objective: Psychiatric symptoms are common and bothersome in individuals with post-COVID-19 syndrome. Because they are often mixed and subthreshold, established treatment regimens cannot be applied. There is an urgent need to identify therapeutics for affected patients. Silexan, a proprietary essential oil from Lavandula angustifolia, has demonstrated efficacy against anxiety, comorbid symptoms, and subthreshold and mixed syndromes. The aim of the current narrative review is to examine the therapeutic potential of Silexan for psychiatric manifestations in patients with post-COVID-19 syndrome.Methods: We reviewed clinical evidence regarding the efficacy of Silexan and first clinical experience in patients with psychiatric symptoms attributable to the post-COVID-19 syndrome. Furthermore, we discussed potential modes of action based on nonclinical data.Results: Silexan has demonstrated therapeutic efficacy for the treatment of generalised anxiety disorder; subsyndromal anxiety disorders; comorbid depressive, somatic, and sleep disturbance symptoms; and mixed anxiety and depression. Emerging clinical experience also suggests the effectiveness and tolerability of Silexan for patients with post-COVID-19 syndrome. This can be explained by the fact that the therapeutic profile of Silexan overlaps with the spectrum of psychiatric symptoms in such patients.Conclusion: Preliminary findings indicate a promising potential of Silexan for the treatment of psychiatric manifestations in patients with post-COVID-19 syndrome.Key pointsAnxiety and mixed neuropsychiatric manifestations are commonly observed in patients with post-COVID-19 syndrome.Silexan has anxiolytic properties and can alleviate comorbid depressive, somatic, and sleep impairment symptoms.Silexan exhibits several biological mechanisms, such as neurotrophic and anti-inflammatory properties, which have the potential to positively impact post-COVID-19 disease.Silexan has a favourable safety profile and high acceptance among patients.Emerging data suggest that Silexan can alleviate neuropsychiatric symptoms in patients with post-COVID-19 syndrome.Silexan should be considered as a therapeutic in patients with psychiatric manifestations of post-COVID-19 syndrome.
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COVID-19 , Óleos Voláteis , Humanos , Síndrome de COVID-19 Pós-Aguda , COVID-19/complicações , Óleos de Plantas , Óleos Voláteis/farmacologiaRESUMO
Phenomenon: This study aimed to investigate how students can develop their understanding of trauma biomechanics by means of technology-enhanced learning-an interactive visualization tool developed to enhance understanding of the biomechanics underlying an injury via dynamic imaging sequences. Approach: Students were invited to explore the content as a learning resource during an interprofessional clinical placement on an orthopedic ward. Thirty volunteer medical, nursing, and physiotherapy/occupational therapy students participated in 10 interprofessional groups of three participants. They were video recorded while interacting with learning software that was divided into five sections: Work Up, General Information, Biomechanical Case Study, Biomechanical Risk Assessment, and Treatment. Investigators probed students' learning experiences via four focus group discussions. A sociomaterial perspective was adopted, directing the analytical focus to how students' made use of talk, gestures, bodies, and material objects to understand the visualized phenomena. Findings: When connecting the visualization to a patient case, certain features of the technology stood out as important for promoting engagement and understanding trauma mechanisms. Decreased tempo, showing the directions and dynamics of trauma biomechanics in slow-motion, and color coding of the strain on the affected structures were especially important for evoking the emotional responses. The visualization tool also supported students' explorations of causal relationships between external forces and their biomedical effects. These features emphasize the sociomaterial relation between the design of the technology and the student activities. Insights: Dynamic visualization of biomechanical events has the potential to improve the understanding of injury mechanisms and specifically to identify anatomical structures at high risk of injury. Dynamic visualizations for educational purposes seem to promote possibilities for learners to contextualize visual representations relative to one's own body. Educational methods and practice need explicit attention and development in order to use the full potential of the visualization technology for learning for the health care professions.
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Comportamento Cooperativo , Relações Interprofissionais , Fenômenos Biomecânicos , Humanos , Estudantes , TecnologiaRESUMO
The diagnosis of anxiety disorders, like other psychiatric disorders also, is operationalised since the introduction of diagnostic manuals. The diagnostic criteria of Generalised Anxiety Disorder (GAD) have been tightened in the last decades. This leads to the exclusion of patients with a high level of anxiety, but not fulfilling certain of the GAD-criteria, from effective treatment. Such so-called subsyndromal, subthreshold or subclinical GAD-states, however, often exhibit a comparable burden of disease like the full syndromal disorder and often tend to develop into the full syndromal disorder. The purpose of this review is - beside systematically reporting the papers found in respective data bases from 2013 onwards - to summarise the relevant data regarding definitions, epidemiology and consequences of subsyndromal anxiety states in order to give a comprehensive review.
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Transtornos de Ansiedade , Ansiedade , Humanos , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , SíndromeRESUMO
Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G>A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.
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Paralisia Facial/genética , Fibrose/genética , Mutação , Oftalmoplegia/genética , Doenças do Sistema Nervoso Periférico/genética , Tubulina (Proteína)/genética , Anormalidades Múltiplas/genética , Adolescente , Adulto , Substituição de Aminoácidos , Arginina , Criança , Pré-Escolar , Paralisia Facial/diagnóstico , Paralisia Facial/fisiopatologia , Feminino , Fibrose/diagnóstico , Fibrose/fisiopatologia , Histidina , Humanos , Lactente , Masculino , Oftalmoplegia/diagnóstico , Oftalmoplegia/fisiopatologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Síndrome , Adulto JovemRESUMO
BACKGROUND: Silexan is a lavender essential oil with established anxiolytic and calming efficacy. Here we asked whether there is a potential for abuse in human patients. METHODS: We carried out a phase I abuse liability single-center, double-blind, 5-way crossover study in healthy users of recreational central nervous system depressants. They received single oral doses of 80 mg (therapeutic dose) and 640 mg Silexan, 2 mg and 4 mg lorazepam (active control) and placebo in randomized order, with 4- to 14-day washout periods between treatments. Pharmacodynamic measures included validated visual analogue scales assessing positive, negative, and sedative drug effects and balance of effects; a short form of the Addiction Research Center Inventory; and a drug similarity assessment. The primary outcome measure was the individual maximum value on the drug liking visual analogue scale during 24 hours post-dose. RESULTS: Forty participants were randomized and 34 were evaluable for pharmacodynamic outcomes. In intraindividual head-to-head comparisons of the drug liking visual analogue scale maximum value, both doses of Silexan were rated similar to placebo whereas differences were observed between Silexan and lorazepam and between placebo and lorazepam (P < .001). These data were supported by all secondary measures of positive drug effects and of balance of effects. Differences between placebo and both doses of Silexan were always negligible in magnitude. Moreover, Silexan showed no sedative effects and was not perceived to be similar to commonly used drugs that participants had used in the past. CONCLUSIONS: Silexan did not exhibit any abuse potential in a standard abuse potential detection screen study and is unlikely to be recreationally abused.
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Ansiolíticos/farmacologia , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Uso Recreativo de Drogas , Adolescente , Adulto , Ansiolíticos/administração & dosagem , Depressores do Sistema Nervoso Central/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Humanos , Lavandula , Lorazepam/farmacologia , Pessoa de Meia-Idade , Óleos Voláteis/administração & dosagem , Óleos de Plantas/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto JovemRESUMO
OBJECTIVES: Predictors for unfavorable treatment outcome in major depressive disorder (MDD) applicable for treatment selection are still lacking. The database of a longitudinal multicenter study on 1079 acutely depressed patients, performed by the German research network on depression (GRND), allows supervised and unsupervised learning to further elucidate the interplay of clinical and psycho-sociodemographic variables and their predictive impact on treatment outcome phenotypes. EXPERIMENTAL PROCEDURES: Treatment response was defined by a change of HAM-D 17-item baseline score ≥50% and remission by the established threshold of ≤7, respectively, after up to eight weeks of inpatient treatment. After hierarchical symptom clustering and stratification by treatment subtypes (serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotic, and lithium augmentation), prediction models for different outcome phenotypes were computed with random forest in a cross-center validation design. In total, 88 predictors were implemented. RESULTS: Clustering revealed four distinct HAM-D subscores related to emotional, anxious, sleep, and appetite symptoms, respectively. After feature selection, classification models reached moderate to high accuracies up to 0.85. Highest accuracies were observed for the SSRI and TCA subgroups and for sleep and appetite symptoms, while anxious symptoms showed poor predictability. CONCLUSION: Our results support a decisive role for machine learning in the management of antidepressant treatment. Treatment- and symptom-specific algorithms may increase accuracies by reducing heterogeneity. Especially, predictors related to duration of illness, baseline depression severity, anxiety and somatic symptoms, and personality traits moderate treatment success. However, prospectives application of machine learning models will be necessary to prove their value for the clinic.
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Transtorno Depressivo Maior , Algoritmos , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Aprendizado de Máquina , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Interest in the topic of termination of life has been growing for 2 decades. After legalisation of active euthanasia and assisted suicide (EAS) in the Netherlands in 2002, movements to implement similar laws started in other European countries. However, many people objected to legalisation on the basis of the experiences in the Netherlands and as a matter of principal. METHODS: This selected and focussed review presents the theoretical discussions about EAS and describes the respective parliamentary discussions in Germany and the data and experiences in the Netherlands. It also considers people with mental disorders in the context of termination-of-life services. RESULTS: So far, only a few European countries have introduced legislation on EAS. Legalisation of EAS in the Netherlands resulted in an unexpectedly large increase in cases. The number of people with mental disorders who terminate their lives on request remains low. CONCLUSIONS: Experience from the Netherlands shows that widening criteria for EAS has problematic consequences.KEY POINTSTermination of life on request, which a subgroup of people support, is a matter of ongoing debate.Because of several problematic aspects, including ethical considerations, only a few countries in the world allow active euthanasia or assisted suicide.Even if euthanasia is well regulated, legalising it can have problematic consequences that are difficult to control, such as an unwanted excessive increase in euthanasia cases.The well-documented experiences with the euthanasia law in the Netherlands serve as an example of what is to be expected when euthanasia is legalised.We need to pay close attention to the relationship between suicide and suicide prevention on the one hand and euthanasia acts and promotion of euthanasia on the other.Further ethical, psychological and legal research is needed. In particular, the role of palliative medicine in societies' approach to end-of-life care must be explored in much more detail.
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Atitude do Pessoal de Saúde , Atitude Frente a Morte , Eutanásia , Legislação Médica , Pessoas Mentalmente Doentes , Suicídio Assistido , Europa (Continente) , Eutanásia/ética , Eutanásia/legislação & jurisprudência , Eutanásia/estatística & dados numéricos , Alemanha , Humanos , Legislação Médica/ética , Legislação Médica/estatística & dados numéricos , Pessoas Mentalmente Doentes/legislação & jurisprudência , Pessoas Mentalmente Doentes/estatística & dados numéricos , Países Baixos , Suicídio Assistido/ética , Suicídio Assistido/legislação & jurisprudência , Suicídio Assistido/estatística & dados numéricosRESUMO
Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.
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Antipsicóticos/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Transtornos Psicóticos/terapia , Esquizofrenia/terapia , Atividades Cotidianas , Adulto , Antipsicóticos/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Recidiva , Indução de Remissão , Esquizofrenia/tratamento farmacológico , Adulto JovemRESUMO
Subthreshold psychiatric disorders do not fully meet the diagnostic criteria of syndromal disorders but may be associated with comparable disability. To investigate the anxiolytic effect of Silexan, an active substance from lavender oil for oral administration, in patients with subthreshold anxiety, a meta-analysis that included all published trials with Silexan in this indication was performed. Three randomised, placebo-controlled trials in subthreshold anxiety disorders (anxiety disorder not otherwise specified, restlessness and agitation, mixed anxiety and depressive disorder) were included. Eligible participants with a baseline Hamilton Anxiety Rating Scale (HAMA) total score ≥ 18 points received 1 × 80 mg/day Silexan or placebo for 10 weeks. Outcomes included the HAMA, the Pittsburgh Sleep Quality Index, the Zung Self-rating Anxiety Scale, the Clinical Global Impressions questionnaire and the SF-36 health status inventory. Data were analysed using meta-analysis based on pooled raw data of individual patients (random effects models). A total of 697 patients were assessed for efficacy. Silexan was superior to placebo in reducing the HAMA total score during 10 weeks' treatment [mean value difference, 95% confidence interval: 3.83 (1.28; 6.37) points]. Superiority was comparably pronounced for psychic and somatic anxiety as well as for observer- and self-rated anxiety. Silexan had a beneficial effect on sleep (secondary to the anxiolytic effect) without causing sedation and improved the patients' health-related quality of life. Adverse event incidence in both treatment groups was comparable [risk ratio: 1.06 (0.85; 1.33)]. Silexan has a significant and clinically meaningful anxiolytic effect in subthreshold anxiety. The results cannot be generalised to other lavender oil products.
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Transtornos de Ansiedade/tratamento farmacológico , Ansiedade/tratamento farmacológico , Óleos Voláteis/farmacologia , Fitoterapia/estatística & dados numéricos , Óleos de Plantas/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento , Humanos , LavandulaRESUMO
Patients with schizophrenia suffer from stigma and discrimination due to their illness. Yet it is not well examined how experiences of stigma and discrimination express at the early illness stage and how they develop subsequently. Therefore, clinical and psycho-social correlates of stigma experiences and perceived stigma are analyzed in patients with first-episode schizophrenia over the course of 1 year after their first in-patient treatment. Questionnaire data assessed within the multi-centre-RCT "First-Episode Study" of the German Research Network on Schizophrenia were analyzed. Patients with first-episode schizophrenia were assessed 8 weeks after their first in-patient treatment (post-acute assessment) and 1 year later. N = 48 (post-acute) and N = 24 (1-year follow-up) patients provided questionnaire data appropriate for analyses, with N = 12 dyads. These data included burden due to stigma experiences (B-STE), perceived stigma (PDDQ), clinical (PANSS, CDSS, CGI, GAF, SAS) and psycho-social factors (LQLP, FSNK-self-esteem, KK-Scale). Cross-lag-correlation models showed a causal relation between stigma experiences (post-acute) and reduced self-esteem after 1 year. Multiple regression models revealed different models for experienced and perceived stigma. Factors associated with higher stigma experiences were older age, worse clinical global impression, better social adjustment, lower self-esteem, and the belief that illness is not driven by chance or fate. The different associations between psycho-social factors and stigma experiences and perceived stigma demonstrate the complexity of this inter-relationship. The results have practical implications for psycho-educational and other therapeutic interventions addressing stigma coping. Since the sample was small and selective, replication studies are needed.
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Hospitalização , Esquizofrenia , Psicologia do Esquizofrênico , Autoimagem , Discriminação Social , Estigma Social , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/terapia , Percepção Social , Adulto JovemRESUMO
INTRODUCTION: The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. METHODS: One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). RESULTS: Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). DISCUSSION: An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.
Assuntos
Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Piperazinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiazóis/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Lumbar spinal stenosis (LSS) can be surgically treated, with variable outcome. Studies have linked socioeconomic factors to outcome, but no nation-wide studies have been performed. This register-based study, including all patients surgically treated for LSS during 2008-2012 in Sweden, aimed to determine predictive factors for the outcome of surgery. METHODS: Clinical and socioeconomic factors with impact on outcome in LSS surgery were identified in several high-coverage registers, e.g., the national quality registry for spine surgery (Swespine, FU-rate 70-90%). Multivariate regression analyses were conducted to assess their effect on outcome. Two patient-reported outcome measures, Global Assessment of leg pain (GA) and the Oswestry Disability Index (ODI), as well as length of sick leave after surgery were analyzed. RESULTS: Clinical and socioeconomic factors significantly affected health outcome (both GA and ODI). Some predictors of a good outcome (ODI) were: being born in the EU, reporting no back pain at baseline, a high disposable income and a high educational level. Some factors predicting a worse outcome were previous surgery, having had back pain more than 2 years, having comorbidities, being a smoker, being on social welfare and being unemployed. CONCLUSIONS: The study highlights the relevance of adding socioeconomic factors to clinical factors for analysis of patient-reported outcomes, although the causal pathway of most predictors' impact is unknown. These findings should be further investigated in the perspective of treatment selection for individual LSS patients. The study also presents a foundation of case mix algorithms for predicting outcome of surgery for LSS. These slides can be retrieved under Electronic Supplementary Material.
Assuntos
Vértebras Lombares/cirurgia , Licença Médica/estatística & dados numéricos , Estenose Espinal/cirurgia , Adulto , Idoso , Dor nas Costas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Medidas de Resultados Relatados pelo Paciente , Prognóstico , Sistema de Registros , Fatores Socioeconômicos , Estenose Espinal/complicações , Estenose Espinal/reabilitação , Suécia , Resultado do TratamentoRESUMO
Background: Suicidal ideations, suicide attempts, and fatal suicides are rare adverse drug reactions to antidepressant drugs, but they essentially are clinically relevant. Drawing on a larger dataset of the European drug surveillance program, the present naturalistic study updates a previous contribution (Stübner et al., 2010). Methods: First an analysis of the comprehensive data collected in 81 psychiatric hospitals from 1993 to 2014 by the European drug surveillance program Arzneimittelsicherheit in der Psychiatrie was made. All documented single cases of suicidal ideations or behavior judged as adverse drug reactions to antidepressant drugs were carefully assessed as to their clinical features and drug prescriptions. Results: Among 219,635 adult hospitalized patients taking antidepressant drugs under surveillance, 83 cases of suicidal adverse drug reactions occurred (0.04%): 44 cases of suicidal ideation, 34 attempted suicides, and 5 committed suicides were documented. Restlessness was present in 42 patients, ego-dystonic intrusive suicidal thoughts or urges in 39 patients, impulsiveness in 22 patients, and psychosis in 7 patients. Almost all adverse drug reactions occurred shortly after beginning antidepressant drug medication or increasing the dosage. Selective serotonin reuptake inhibitors caused a higher incidence of suicidal ideation and suicidal behavior as adverse drug reactions than noradrenergic and specific serotonergic antidepressants or tricyclic antidepressants, as did monotherapy consisting of one antidepressant drug, compared to combination treatments. Conclusions: The study supports the view that antidepressant drug-triggered suicidal ideation and suicidal behavior (primarily with selective serotonin reuptake inhibitors) are rare. Special clinical features (restlessness, ego-dystonic thoughts or urges, impulsiveness) may be considered as possible warning signs. A combination therapy might be preferable to antidepressant drug monotherapy when beginning treatment.