Step away from depression-results from a multicenter randomized clinical trial with a pedometer intervention during and after inpatient treatment of depression.

Evidence for the effectiveness of physical activity (PA) in the treatment of depression prevails for outpatients with mild and moderate symptom levels. For inpatient treatment of severe depression, evidence-based effectiveness exists only for structured and supervised group PA interventions. The Step Away from Depression (SAD) study investigated the effectiveness of an individual pedometer intervention (PI) combined with an activity diary added to inpatient treatment as usual (TAU). In this multicenter randomized controlled trial, 192 patients were randomized to TAU or TAU plus PI. The two primary outcomes at discharge were depression-blindly rated with the Montgomery-Åsberg Depression Rating Scale (MADRS)-and average number of daily steps measured by accelerometers. Secondary outcomes were self-rated depression and PA, anxiety, remission and response rates. Multivariate analysis of variance (MANOVA) revealed no significant difference between both groups for depression and daily steps. Mean MADRS scores at baseline were 29.5 (SD = 8.3) for PI + TAU and 28.8 (SD = 8.1) for TAU and 16.4 (SD = 10.3) and 17.2 (SD = 9.9) at discharge, respectively. Daily steps rose from 6285 (SD = 2321) for PI + TAU and 6182 (SD = 2290) for TAU to 7248 (SD = 2939) and 7325 (SD = 3357). No differences emerged between groups in secondary outcomes. For severely depressed inpatients, a PI without supervision or further psychological interventions is not effective. Monitoring, social reinforcement and motivational strategies should be incorporated in PA interventions for this population to reach effectiveness.

Guideline for schizophrenia: implementation status and attitude toward an upcoming living guideline.

The implementation status of clinical guidelines is, despite their important role in connecting research with practice, frequently not satisfactory. This study aims to investigate the implementation status of the current German guideline for schizophrenia. Moreover, the attitude toward a living guideline has been explored for the first time by presenting screenshots of the German schizophrenia guideline transferred to a digital living guideline format called MAGICapp. A cross-sectional online survey was performed under the participation of 17 hospitals for psychiatry and psychosomatic medicine in Southern Germany and one professional association for German neurologists and psychiatrists. 439 participants supplied sufficient data for analysis. 309 provided complete data sets. Regarding the current guideline for schizophrenia and key recommendations, a large awareness-to-adherence gap was found. Group comparisons between different professions (caregivers, medical doctors, psychologists/psychotherapists, psychosocial therapists) detected differences in the implementation status showing higher awareness and agreement with the schizophrenia guideline and its key recommendations among medical doctors compared to psychosocial therapists and caregivers. Moreover, we detected differences in the implementation status of the guideline as a whole and its key recommendations between specialist and assistant doctors. The attitude toward an upcoming living guideline was mostly positive, especially among younger healthcare professionals. Our findings confirm an awareness-to-adherence gap, not only for the current schizophrenia guideline in general but also for its key recommendations with apparent differences between professions. Overall, our results show promising positive attitudes toward the living guideline for schizophrenia among healthcare providers, suggesting that a living guideline may be a supportive tool in everyday clinical practice.

Conventional and living guideline for schizophrenia: barriers and facilitating factors in guideline implementation.

This study aims to investigate the barriers and facilitators to guideline adherence for the print format of the German schizophrenia guideline as well as for the concept of a digital living guideline for the first time. For this purpose, the schizophrenia guideline was transferred to a digital guideline format within the web-based tool MAGICapp. An online survey was performed under participation of mental healthcare professionals (medical doctors, psychologists/psychotherapists, psychosocial therapists, caregivers) in 17 hospitals for psychiatry in Southern Germany and a professional association for German neurologists and psychiatrists. 524 participants opened the survey, 439 completed the demographic questions and commenced the content-related survey and 309 provided complete data sets. Results indicate a higher occurrence of knowledge-related barriers for the living guideline. The print version is associated with more attitude-related and external barriers. Older professionals reported more attitude-related barriers to a living guideline compared to younger professionals. Differences between professions regarding barriers were found for both formats. Various barriers exist for both guideline formats and a need for facilitators was expressed across professions. Many of the mentioned obstacles and facilitators can be more easily addressed with living guidelines. However, also living guidelines face barriers. Thus, the introduction of these new formats alone cannot lead to sustainable behavior change regarding guideline adherence. Yet, living guidelines seem to be a cornerstone to improved and tailored guideline implementation as they facilitate to keep recommendations up to date and to address the need of individual professional groups.

Evaluation of evidence grades in psychiatry and psychotherapy guidelines.

BACKGROUND: Information regarding the distribution of evidence grades in psychiatry and psychotherapy guidelines is lacking. Based on the German evidence- and consensus- based (S3) psychiatry and psychotherapy and the Scottish Intercollegiate Guidelines Network (SIGN) treatment guidelines, we aimed to specify how guideline recommendations are composed and to what extent recommendations are evidence-based. METHODS: Data was collected from all published evidence- and consensus-based S3-classified psychiatry and psychotherapy guidelines. As control conditions, data from German neurology S3-classified guidelines as well as data from recent SIGN guidelines of mental health were extracted. Two investigators reviewed the selected guidelines independently, extracted and analysed the numbers and levels of recommendations. RESULTS: On average, 45.1% of all recommendations are not based on strong scientific evidence in German guidelines of psychiatry and psychotherapy. A related pattern can be confirmed for SIGN guidelines, where the mean average of recommendations with lacking evidence is 33.9%. By contrast, in the German guidelines of neurology the average of such recommendations is 16.5%. A total of 24.5% of all recommendations in the guidelines of psychiatry and psychotherapy are classified as level A recommendations, compared to 31.6% in the field of neurology and 31.1% in the SIGN guidelines. Related patterns were observed for B and 0 level recommendations. CONCLUSION: Guidelines should be practical tools to simplify the decision-making process based on scientific evidence. Up to 45% of all recommendations in the investigated guidelines of psychiatry and psychotherapy are not based on strong scientific evidence. The reasons for this high number remain unclear. Possibly, only a limited number of studies answer clinically relevant questions. Our findings thereby question whether guidelines should include non-evidence-based recommendations to be methodologically stringent and whether specific processes to develop expert-opinion statements must be implemented.

Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia.

Schizophrenia is a severe neuropsychiatric disease that is associated with neurobiological alterations in multiple brain regions and peripheral organs. Negative symptoms and cognitive deficits are present in about half of patients and are difficult to treat, leading to an unfavorable functional outcome. To investigate the impact of aerobic exercise on various neurobiological parameters, we conducted a narrative review. Add-on aerobic exercise was shown to be effective in improving negative and general symptoms, cognition, global functioning, and quality of life in schizophrenia patients. Based on findings in healthy individuals and animal models, this qualitative review gives an overview of different lines of evidence on how aerobic exercise impacts brain structure and function and molecular mechanisms in patients with schizophrenia and how its effects could be related to clinical and functional outcomes. Structural magnetic resonance imaging studies showed a volume increase in the hippocampus and cortical regions in schizophrenia patients and healthy controls after endurance training. However, results are inconsistent and individual risk factors may influence neuroplastic processes. Animal studies indicate that alterations in epigenetic mechanisms and synaptic plasticity are possible underlying mechanisms, but that differentiation of glial cells, angiogenesis, and possibly neurogenesis may also be involved. Clinical and animal studies also revealed effects of aerobic exercise on the hypothalamus-pituitary-adrenal axis, growth factors, and immune-related mechanisms. Some findings indicate effects on neurotransmitters and the endocannabinoid system. Further research is required to clarify how individual risk factors in schizophrenia patients mediate or moderate the neurobiological effects of exercise on brain and cognition. Altogether, aerobic exercise is a promising candidate in the search for pathophysiology-based add-on interventions in schizophrenia.

From conventional to living guidelines - faster updates for better informed guidance? A scoping review.

OBJECTIVE: The goal of living guidelines is keeping recommendations in guidelines up-to-date as new evidence becomes available. This review aims at scoping the prevalence and formal characteristics of living guidelines in the field of medicine and explore differences between formats. METHODS: A selective search of living guidelines in MEDLINE via PubMed, Google Scholar and six relevant online repositories for guidelines (MAGICApp, AWMF, GIN, NICE, WHO-Iris, BIGG) was conducted. Authors and editors were contacted to receive previous non-living guideline versions. Living guidelines were subsequently analyzed according to pre-defined methodological criteria as described below (inter-comparison). Differences between living and their conventional (non-living) versions were assessed (intra-comparison). RESULTS: 83 living guidelines were identified and selected for further screening, out of which 26 were eligible for analysis. 61.5% were new publications (de-novo guidelines) and 38.5% updates of pre-existing guidelines. There are some concepts defining, for example, the update cycle (AWMF, maximum of 12 months) but not all living guidelines follow or refer to existing concepts. The analysis shows that living guidelines in line with the established standards for (non-living) clinical guidelines involve an evidence standard, an extensive consensus process (often in the form of a Delphi process), and the inclusion of stakeholders (patients/relatives) in the development process, despite the high frequency of updates. When comparing living and conventional guidelines with the descriptive approach changes were found in update frequency (being more frequent with living guidelines, annually at the latest) and publication format (towards more digital) and public consultation (living guidelines offered more possibilities), no substantial methodological differences were observed in the description of consensus processes, changes in number of recommendations, inclusion of patient representatives. Given the small number of comparable pairs, the results reflect a tendency in the analyzed sample. CONCLUSIONS: The definition and development of living guidelines varied. Standardization (i. e. in the form of a checklist, procedure template) is needed to assess quality of the living process.

Structured implementation of digital, systematically updated guideline recommendations for enhanced adherence in schizophrenia (SISYPHOS)-protocol of a cluster-randomized trial.

BACKGROUND: Despite high acceptance rates in the field, the implementation of the 2019 published German evidence and consensus-based S3 guideline is unsatisfactory. This study aims to assess the superiority of an adaptive online version with a better visualization of the recommendations in terms of guideline conformity, application of shared decision making, and digital health expertise compared to the classic pdf print version of the guideline. METHODS: The study is a multicenter, controlled, cluster-randomized trial with two arms: one arm investigating the implementation of the German schizophrenia guideline in form of a digital format (intervention group using the evidence ecosystem MAGICapp), the other arm in form of the classic print pdf version (control group). Physicians and psychologists working in specialized hospitals will be included in the study. The guideline-knowledge before and after the intervention is defined as primary outcome measure. Secondary endpoints include digital health expertise and application of shared decision making. DISCUSSION: This is the first study evaluating if an adaptive-digital version of the schizophrenia guideline is superior to the classic pdf print version. Therefore, the guideline is digitally prepared in the evidence-ecosystem MAGICapp, which covers the whole process of the development of a living guideline. We intend to use the results of the cluster-randomized trial for developing the German S3 guideline for schizophrenia in form of a living guideline in future. TRIAL REGISTRATION: The study is registered (10 May 2022) in the German Clinical Trials Register (DRKS) and the WHO International Clinical Trials Registry Platform (ICTRP) under registration number DRKS00028895 .

Efficacy and safety of clozapine in psychotic disorders-a systematic quantitative meta-review.

A recent increase in the literature regarding the evidence base for clozapine has made it increasingly difficult for clinicians to judge "best evidence" for clozapine use. As such, we aimed at elucidating the state-of-the-art for clozapine with regard to efficacy, effectiveness, tolerability, and management of clozapine and clozapine-related adverse events in neuropsychiatric disorders. We conducted a systematic PRISMA-conforming quantitative meta-review of available meta-analytic evidence regarding clozapine use. Primary outcome effect sizes were extracted and transformed into relative risk ratios (RR) and standardized mean differences (SMD). The methodological quality of meta-analyses was assessed using the AMSTAR-2 checklist. Of the 112 meta-analyses included in our review, 61 (54.5%) had an overall high methodological quality according to AMSTAR-2. Clozapine appears to have superior effects on positive, negative, and overall symptoms and relapse rates in schizophrenia (treatment-resistant and non-treatment-resistant subpopulations) compared to first-generation antipsychotics (FGAs) and to pooled FGAs/second-generation antipsychotics (SGAs) in treatment-resistant schizophrenia (TRS). Despite an unfavorable metabolic and hematological adverse-event profile compared to other antipsychotics, hospitalization, mortality and all-cause discontinuation (ACD) rates of clozapine surprisingly show a pattern of superiority. Our meta-review outlines the superior overall efficacy of clozapine compared to FGAs and most other SGAs in schizophrenia and suggests beneficial efficacy outcomes in bipolar disorder and Parkinson's disease psychosis (PDP). More clinical studies and subsequent meta-analyses are needed beyond the application of clozapine in schizophrenia-spectrum disorders and future studies should be directed into multidimensional clozapine side-effect management to foster evidence and to inform future guidelines.

rTMS and tDCS for the treatment of catatonia: A systematic review.

BACKGROUND: Catatonia is a potentially life threatening syndrome in various psychiatric disorders. As first line treatment, benzodiazepines and electroconvulsive therapy (ECT) are recommended. In some cases, benzodiazepines are ineffective and ECT is not available or contraindicated. Therefore, the search for new and alternative treatment strategies is of great importance. OBJECTIVE: To review the evidence for alternative neurostimulation treatment strategies (rTMS and tDCS) for catatonia according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. METHOD: We performed a systematic literature search in several electronic databases. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov database to detect registered studies. RESULTS: We identified nine publications on rTMS treatment and four publications on tDCS in catatonia. Most of the publications reported clinically relevant improvement of catatonic symptoms. Only two publications reported insufficient improvement. The available Bush-Francis Catatonia Rating Scale scores showed statistical significant improvement following rTMS and tDCS. We could not identify any finished clinical studies or case series, dedicated to this topic. We also could not identify any publications that compared first line treatment options with rTMS or tDCS. CONCLUSIONS: Based on the case report literature, rTMS and tDCS might be promising alternative treatment strategies for patients who do not respond to benzodiazepines or in case ECT is not available or contraindicated. There are even hints that rTMS or tDCS might be an option in patients who respond to ECT but need long-term treatment to control catatonic symptoms. Further clinical trials are needed to allow for an evidence-based evaluation of potential risks and benefits of rTMS and tDCS for catatonia.

Nonpharmacological treatment of dyscognition in schizophrenia: effects of aerobic exercise
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Cognitive symptoms are a core feature of schizophrenia and are related to an unfavorable disease outcome. So far, there are no satisfactory pharmacological approaches to address cognitive symptoms. For some time now, aerobic exercise has been demonstrated in various trials to be a promising candidate for this indication. The aim of this brief qualitative review was to present the most recent meta-analyses regarding the capacity of exercise to improve cognition in schizophrenia patients. Additionally, we give a short overview of the effects in other conditions, like healthy subjects and patients with major depression. We conducted a focused literature search using the PubMed database, concentrating on meta-analyses which are based on a systematic search. The most recent meta-analysis investigating the efficacy of aerobic exercise on cognitive impairments in schizophrenia patients provides evidence that exercise has positive effects on cognitive functioning in this population. However, the effect seems not to be specific; there were positive findings regarding healthy subjects and patients with depressive disorders as well, even if they were less consistent. As most available trials have a small to modest sample size and have no consensus with regard to the intervention regime, nor to the assessment of cognition, the findings are difficult to generalize. In the future, standardized clinical trials focusing on the long-term effects of exercise are needed to evaluate whether the improvements in cognition are sustainable.
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Los síntomas cognitivos constituyen una característica central de la esquizofrenia y se relacionan con un resultado desfavorable de la enfermedad. Hasta la fecha, no hay enfoques farmacológicos efectivos para abordar los síntomas cognitivos. Desde hace algún tiempo, se ha demostrado en varios ensayos que el ejercicio aeróbico es un candidato prometedor para esta indicación. El objetivo de esta breve revisión cualitativa fue presentar los resultados de meta-análisis más recientes sobre la capacidad del ejercicio para mejorar la cognición en pacientes con esquizofrenia. Además, se ofrece una breve descripción de los efectos del ejercicio en sujetos sanos y en pacientes con depresión mayor. Se realizó una búsqueda bibliográfica dirigida en la base de datos PubMed, focalizada en estudios de meta-análisis basados en una revisión sistemática. El meta-análisis más reciente que investiga la eficacia del ejercicio aeróbico en el deterioro cognitivo en pacientes con esquizofrenia proporciona evidencia de que el ejercicio tiene efectos positivos sobre el funcionamiento cognitivo en esta población. Sin embargo, el efecto no parece ser específico; también hubo resultados positivos -aunque menos constantes- en sujetos sanos y en pacientes con trastornos depresivos. Los hallazgos son difíciles de generalizar ya que la mayoría de los ensayos disponibles tienen un tamaño muestral pequeño o moderado y no hay consenso con respecto al tipo de intervención, ni a la evaluación de la cognición. En el futuro, se requiere de ensayos clínicos estandarizados que se centren en los efectos a largo plazo del ejercicio para evaluar si las mejorías en la cognición son duraderas.

Les symptômes cognitifs sont une caractéristique essentielle de la schizophrénie et sont liés à une évolution péjorative de la maladie. Il n'existe pas à ce jour de traitement pharmacologique satisfaisant pour les symptômes cognitifs. Différentes études ont montré depuis un certain temps maintenant, que l'exercice aérobie était prometteur dans cette indication. Cette brève mise au point qualitative a pour but de présenter les méta-analyses les plus récentes sur la capacité d'amélioration de la cognition des patients schizophrènes par l'exercice physique. Nous faisons en outre une revue rapide des effets dans d'autres circonstances comme les sujets sains et les patients souffrant de dépression majeure. Nous nous sommes concentrés sur des méta-analyses basées sur une recherche systématique dans la base de données PubMed pour réaliser une recherche ciblée de la littérature. Les méta-analyses les plus récentes à propos de l'efficacité de l'exercice aérobie sur les déficits cognitifs dans la schizophrénie montrent que l'exercice a des effets positifs sur le fonctionnement cognitif dans cette population. Cependant, ces effets ne semblent pas spécifiques ; les résultats sont également positifs pour les sujets sains et les patients atteints de troubles dépressifs même si ils sont moins constants. Il est difficile de généraliser les résultats car la taille des échantillons de la plupart des études disponibles est petite voire négligeable et il n'y a pas de consensus en ce qui concerne les traitements ni l'évaluation de la cognition. À l'avenir, des études cliniques standardisées sur les effets à long terme de l'exercice sont nécessaires pour évaluer la durabilité des améliorations de la cognition.

A systematic review of trials investigating strength training in schizophrenia spectrum disorders.

This systematic review analyzed strength training (ST) in patients with schizophrenia. Two independent reviewers searched PubMed and CENTRAL. Only two studies reported on the effects of isolated ST. ST with a single exercise did not improve psychopathology but walking performance. ST for several large muscle groups significantly improved muscle strength and psychopathology. To date, no treatment recommendations can be made for ST. Consistent with recommendations for healthy people combined strength and endurance training can be recommended for schizophrenia. For higher transparency regarding trainings aspects, we recommend for future studies to use the sport science checklist proposed in this paper.

Effects of Aerobic Exercise on Metabolic Syndrome, Cardiorespiratory Fitness, and Symptoms in Schizophrenia Include Decreased Mortality.

Schizophrenia is a severe psychiatric disorder with a lifetime prevalence of about 1%. People with schizophrenia have a 4-fold higher prevalence of metabolic syndrome than the general population, mainly because of antipsychotic treatment but perhaps also because of decreased physical activity. Metabolic syndrome is a risk factor for cardiovascular diseases, and the risk of these diseases is 2- to 3-fold higher in schizophrenia patients than in the general population. The suicide risk is also higher in schizophrenia, partly as a result of depression, positive, and cognitive symptoms of the disease. The higher suicide rate and higher rate of cardiac mortality, a consequence of the increased prevalance of cardiovascular diseases, contribute to the reduced life expectancy, which is up to 20 years lower than in the general population. Regular physical activity, especially in combination with psychosocial and dietary interventions, can improve parameters of the metabolic syndrome and cardiorespiratory fitness. Furthermore, aerobic exercise has been shown to improve cognitive deficits; total symptom severity, including positive and negative symptoms; depression; quality of life; and global functioning. High-intensity interval endurance training is a feasible and effective way to improve cardiorespiratory fitness and metabolic parameters and has been established as such in somatic disorders. It may have more beneficial effects on the metabolic state than more moderate and continuous endurance training methods, but to date it has not been investigated in schizophrenia patients in controlled, randomized trials. This review discusses physical training methods to improve cardiorespiratory fitness and reduce metabolic syndrome risk factors and symptoms in schizophrenia patients. The results of studies and future high-quality clinical trials are expected to lead to the development of an evidence-based physical training program for patients that includes practical recommendations, such as the optimal length and type of aerobic exercise programs and the ideal combination of exercise, psychoeducation, and individual weight management sessions.