Stefan Leucht

Technische Universität München | TUM · Klinik und Poliklinik für Psychiatrie und Psychotherapie

Background The relative treatment effects estimated from network meta-analysis can be employed to rank treatments from the most preferable to the least preferable option. These treatment hierarchies are typically based on ranking metrics calculated from a single outcome. Some approaches have been proposed in the literature to account for multiple o...

Background and Hypothesis Negative symptoms are very important for the overall loss of functioning observed in patients with schizophrenia. There is a need for valid tools to assess these symptoms. Study Design We used the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) systematic review guideline to evaluate...

Objective There is no standard tool for assessing risk of bias (RoB) in prevalence studies. For the purposes of a living systematic review during the COVID-19 pandemic, we developed a tool to evaluate RoB in studies measuring the prevalence of mental health disorders (RoB-PrevMH) and tested inter-rater reliability. Methods We decided on items and...

This letter serves to remind readers of Schizophrenia Research that like all measures in psychiatry, the Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987) used for assessing symptom severity of patients with schizophrenia is contaminated with error. According to true-score theory (Lord and Novick, 1968; Novick, 1966), the PANSS total s...

Examining the heterogeneity of negative symptoms of schizophrenia contributes to the identification of available treatment targets. Generally, prior evidence classified three to four symptom treatment response trajectory groups over the course of positive symptoms, yet, no evidence exists regarding the heterogeneity of medium-term response to predo...

Background: Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and...

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...

Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperido...

Background Quick symptomatic remission after the onset of psychotic symptoms is critical in schizophrenia treatment, determining the subsequent disease course and recovery. In this context, only every second patient with acute schizophrenia achieves symptomatic remission within three months of initiating antipsychotic treatment. The potential indic...

Background Negative symptoms of schizophrenia are linked with poor functioning and quality of life. Therefore, appropriate measurement tools to assess negative symptoms are needed. The NIMH-MATRICS Consensus defined five domains for negative symptoms, which The Brief Negative Symptom Scale (BNSS) covers. Methods We used the COSMIN guidelines for s...

Background and hypothesis: Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. Study design: We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injecta...

Background Psychometric network analysis is an alternative theoretically‐driven analytic approach that has the potential to conceptualize cognitive impairment in Alzheimer’s disease differently than was previously assumed and consequently detect unknown treatment effects. Method Based on individual participant data, extracted from three double‐bli...

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying...

Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long-term efficacy of antipsychotic drugs in acutely ill patients using network meta-analysis. We searched the Cochrane Schizophrenia Group register up to March 6, 2022 for randomized, blinded tr...

This article sensitizes clinicians and researchers to the uncertainty inherent in clinical measures and points the problems that it poses for the assessment of a response and, more importantly, for the computation of responder rates in clinical trials, using the Positive and Negative Syndrome Scale (PANSS) as an example. We offer a new, promising a...

In recent years, network meta-analyses have been increasingly carried out to inform clinical guidelines and policy. This approach is under constant development, and a broad consensus on how to carry out several of its methodological and statistical steps is still lacking. Therefore, different working groups might often make different methodological...

Antipsychotic-induced akathisia is severely distressing. We aimed to investigate relationships between antipsychotic doses and akathisia risk. We searched for randomised controlled trials that investigated monotherapy of 17 antipsychotics in adults with acute schizophrenia until 06 March 2022. The primary outcome was the number of participants with...

Despite the clear rationale for applying shared decision-making in the context of the preference sensitive decision for or against antipsychotics and the upswing of patient decision aids (pDAs) to support this process, there is still a lack of knowledge regarding which key features are crucial for pDAs in schizophrenia treatment. A scoping review a...

Background and hypothesis: This analysis examined the relationship between cannabis use, compliance with antipsychotics and risk for relapse in patients in remission following a first episode of schizophrenia, schizophreniform, or schizoaffective disorder. Study design: Analyses were performed on data from a large European study on first episode...

Objective: In the majority of randomized controlled trials (RCTs) conducted in schizophrenia populations, patients suffering from a substance use disorder (SUD) or suicidality are excluded. Excluding these patients from RCTs might impact the generalizability of results. The aim of this study is to determine whether excluding patients with suicidali...

Background There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, convention...

Objectives: Decision aids (DAs) are promising tools to foster evidence-based shared decision-making between practitioners and service users. Nevertheless, it is still obscure how an evidence-based DA for people with severe mental illness, especially psychosis, should look in an inpatient treatment setting to be useful and feasible. Therefore, we c...

Background: Predicting relapse for individuals with psychotic disorders is not well established, especially after discontinuation of antipsychotic treatment. We aimed to identify general prognostic factors of relapse for all participants (irrespective of treatment continuation or discontinuation) and specific predictors of relapse for treatment di...

Introduction Guidelines recommend clozapine for treatment-resistant schizophrenia. However, meta-analysis of aggregate data (AD) did not demonstrate higher efficacy of clozapine compared with other second-generation antipsychotics but found substantial heterogeneity between trials and variation between participants in treatment effects. Therefore,...

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 pres...

Rationale Weight gain is a frequent side effect of treatment with SGAs (second-generation antipsychotics) and a leading cause for nonadherence. Several candidate genes have been identified that could influence the amount of AIWG (antipsychotic-induced weight gain). The polymorphism rs17782313 near the MC4R (human melanocortin 4 receptor gene) was s...

Objective Biases affect how certain we are about the available evidence, however no standard tool for assessing the risk of bias (RoB) in prevalence studies exists. For the purposes of a living systematic review on prevalence of mental health disorders during the COVID-19 pandemic, we developed a RoB tool to evaluate prevalence studies in mental he...

Background: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medicatio...

Network meta-analysis (NMA) usually provides estimates of the relative effects with the highest possible precision. However, sparse networks with few available studies and limited direct evidence can arise, threatening the robustness and reliability of NMA estimates. In these cases, the limited amount of available information can hamper the formal...

Metabolic side effects of antipsychotic drugs can have serious health consequences and may increase mortality. Although persons with schizophrenia often take these drugs for a long time, their mid‐ to long‐term metabolic effects have been studied little so far. This study aimed to evaluate the mid‐ to long‐term metabolic side effects of 31 antipsyc...

Seizures are suspected to be side effects of antipsychotics. To examine a possible causal relationship, we compared the risk of seizures on second-generation antipsychotics to the risk on placebo in randomized controlled clinical trials (RCTs) across diagnostic groups. The primary outcome was any seizure reported as International Conference on Harm...

Importance Predictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices....

Background: Subjective response (SR) to antipsychotic medication is relevant for quality of life, adherence and recovery. Here, we evaluate (1) the extent of variation in SR in patients using a single antipsychotic; (2) the association between subjective and symptomatic response; and (3) predictors of SR. Methods: Open-label, single treatment co...

Functioning is recognized as a key treatment goal in alleviating the burden of schizophrenia. Psychological interventions can play an important role in improving functioning in this population, but the evidence on their efficacy is limited. We therefore aimed to evaluate the effect of psychological interventions in functioning for patients with sch...

Background: Antipsychotic drugs are the mainstay treatment for schizophrenia, yet they are associated with diverse and potentially dose-related side effects which can reduce quality of life. For this reason, the lowest possible doses of antipsychotics are generally recommended, but higher doses are often used in clinical practice. It is still uncl...

Background: As comparatively few trials in subgroups of patients with schizophrenia have been done, clinicians need to know whether they can rely on the results of randomised controlled trials (RCTs) in the general population of patients with schizophrenia. We aimed to compare the efficacy and side-effects of antipsychotic drugs in different subgr...

Background: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. Purpose: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose–response relations with characteristics of the pandemic and its containment. Data Sour...

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 decisio...

Cognitive impairment in schizophrenia represents one of the main obstacles to clinical and functional recovery. This expert group paper brings together experts in schizophrenia treatment to discuss scientific progress in the domain of cognitive impairment to address cognitive impairments and their consequences in the most effective way. We report o...

Background: In clinical practice, different antipsychotics can be combined in the treatment of people with schizophrenia (polypharmacy). This strategy can aim at increasing efficacy, but might also increase the adverse effects due to drug-drug interactions. Reducing polypharmacy by withdrawing one or more antipsychotics may reduce this problem, bu...

Background: Patient characteristics may predict the progression of Alzheimer's disease (AD) and may moderate the effects of donepezil. Objective: To build a personalized prediction model for patients with AD and to estimate patient-specific treatment effects of donepezil, using individual patient characteristics. Methods: We systematically sea...

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 Pu...

Introduction The Young Mania Rating Scale (YMRS) is the gold standard to assess manic symptoms of bipolar disorder, yet the clinical meaning of scores is unknown. To clinically understand and interpret YMRS scores, we examined linkages between the total and change scores of YMRS with the Clinical Global Impression (CGI) ratings. Methods Individual...

Negative symptoms, such as lack of motivation or social withdrawal, are highly prevalent and debilitating in patients with schizophrenia. Underlying mechanisms of negative symptoms are incompletely understood, thereby preventing the development of targeted treatments. We hypothesized that in patients with schizophrenia during psychotic remission, i...

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To investigate the effects of CBT for schizophrenia when administered without a concomitant pharmacological treatment with antipsychotics. Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Background and Hypothesis Meta-analyses have shown that the majority of patients with schizophrenia who have not improved after 2 weeks of treatment with an antipsychotic drug are unlikely to fully respond later. We hypothesized that switching to another antipsychotic with a different receptor binding profile is an effective strategy in such a situ...

Background: Antipsychotics are the treatment of choice in the therapy of schizophrenia. These drugs can be associated with changes in heart rate, but this question has never been examined systematically. Objective: We aimed to analyse changes in heart rate during treatment with antipsychotics using the frequency of tachycardia and bradycardia ev...

Background Choosing an antipsychotic medication is an important medical decision in the treatment of schizophrenia. This decision requires risk-benefit assessments of antipsychotics, and thus, shared-decision making between physician and patients is strongly encouraged. Although the efficacy and side-effect profiles of antipsychotics are well-estab...

Objective A network meta-analysis (NMA) usually assesses multiple outcomes across several treatment comparisons. The Vitruvian plot aims to facilitate communication of multiple outcomes from NMAs to patients and clinicians. Methods We developed this tool following the recommendations on the communication of benefit–risk information from the availa...

Antipsychotic drugs are the mainstay of treatment of schizophrenia, and are known to reduce acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotics are effective for relapse prevention, compared to withdrawing these agents for people with schizophrenia or schizophrenia-like psych...

Background and Hypothesis Optimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study Methods We studied the risk of rehospitalizati...

Introduction Minimum clinically important difference (MCID) is a measure that defines the minimum amount of change in an objective score of a clinical test that must be reached for that change to be clinically noticeable. We aimed to find the MCID for patients with predominantly negative symptoms of schizophrenia at its earliest occurrence. Method...

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients...

Psychometric network analysis is an alternative theoretically-driven analytic approach that has the potential to conceptualize cognitive impairment in Alzheimer's disease differently than was previously assumed and consequently detect unknown treatment effects. Based on individual participant data, extracted from three double-blind, randomized plac...

Objective: Historically, assessment of the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) has had several foci: 1) calculation of reliability indexes, 2) extraction of subdimensions from the scale, and 3) assessment of the validity of the total score. In this study, we aimed to examine the scalability and to assess the...

Changes over 50 years of research on antipsychotics in schizophrenia have occurred. A scientometric synthesis of such changes over time and a measure of researchers' networks and scientific productivity is currently lacking. We searched Web of Science Core Collection from inception until November 5, 2021, using the appropriate key. Our primary obje...

The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept “Precision in Mental Health (PriMe): Understanding, predicting, and preventi...

Background Adverse events can occur after antipsychotic discontinuation but evidence from antipsychotic drug trials is scarce. We aimed to estimate the occurrence of adverse events after discontinuing antipsychotics. Methods For this two-stage individual participant data meta-analysis, we searched the Yale University Open Data Access Project's dat...

Background Combining antipsychotics is common in schizophrenia treatment, despite evidence-based guidelines generally not recommending such practice. Otherwise, evidence remains inconclusive, especially regarding specific combinations. The trial aimed to test whether a combination of amisulpride plus olanzapine is more effective than either interve...

Background Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this gap with a dose-response meta-analysis. Methods We searched multiple electronic databases (last update search June 2021) for all fixed-dose studies that investigated 16...

Background Schizophrenia is a common, severe, and usually chronic disorder. Maintenance treatment with antipsychotic drugs can prevent relapse but also causes side-effects. We aimed to compare the efficacy and tolerability of antipsychotics as maintenance treatment for non-treatment resistant patients with schizophrenia. Methods In this systematic...

Background Family interventions are efficacious for relapse prevention in schizophrenia. Multiple different models have been developed. We aimed to compare the efficacy, acceptability, and tolerability of family interventions for relapse prevention in schizophrenia. Methods In this systematic review and network meta-analysis, we searched for rando...

The association between early improvement and subsequent change in cognition is unexamined in antidementia clinical trials. We aimed to examine the consequences of early-response to antidementia medication in Alzheimer's disease. Participant-level data were analyzed from five pivotal clinical trials of donepezil for Alzheimer's disease lasting up t...

Importance: Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an effi...

The CATIE schizophrenia trial was a very influential randomized controlled trial in patients with chronic schizophrenia. Patients were followed for up to 18 months under treatment with a randomly assigned antipsychotic. The primary endpoint, time to discontinuation of treatment for any reason, is influenced by individual patient characteristics, ex...

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 advers...

In Reply Replication is the essence of science. It is therefore important that Højlund and colleagues,¹ who used a different meta-analytic method and slightly different inclusion criteria from ours, had similar findings in that standard doses (in our analysis, 5 mg risperidone equivalent) were more effective than lower ones (also see our Supplement...