Antipsychotic drug dosing and study discontinuation in schizophrenia: A systematic review and dose-response meta-analysis.

Background: High discontinuation rates compromise the effectiveness of treatment regimens for schizophrenia, because consistent medication adherence is essential for the efficacy of antipsychotics. Understanding the relationship between antipsychotic doses and discontinuation rates is important. This study explores this relationship to identify doses that maximize treatment adherence and minimize discontinuation.

Efficacy of clozapine versus second-generation antipsychotics in people with treatment-resistant schizophrenia: a systematic review and individual patient data meta-analysis.

Background: Clozapine is recommended by national and international guidelines for people with treatment-resistant schizophrenia. However, available meta-analyses of randomised controlled trials have not shown superior efficacy of clozapine when compared with other second-generation antipsychotics, with heterogeneity identified between the original studies. We aimed to use individual patient data (IPD) to account for potential reasons of variability and to synthesise an adjusted estimate for the difference in efficacy between clozapine and other second-generation antipsychotics for treatment-resistant schizophrenia.

Muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis: protocol for a systematic review and meta-analysis.

Background: Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.

Triangulating evidence from the GALENOS living systematic review on trace amine-associated receptor 1 (TAAR1) agonists in psychosis.

Background: Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

Aims: To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

Method: This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis).

Evidence for music therapy and music medicine in psychiatry: transdiagnostic meta-review of meta-analyses.

Background: Music therapy is a commonly used intervention added to usual care for psychiatric disorders.

Aims: We review the evidence for music therapy and assess its efficacy as an adjunct therapy across psychiatric disorders.

Method: A systematic literature search was conducted in four scientific databases to identify relevant meta-analyses.

Efficacy and tolerability of blonanserin in schizophrenia: A systematic review and meta-analysis of randomized controlled trials.

Background: Blonanserin is approved for treating schizophrenia in Japan, South Korea, India, and China. We aimed to synthesize the efficacy and tolerability of blonanserin compared to other antipsychotics.

Methods: A systematic review and pairwise meta-analysis were conducted using the Cochrane Schizophrenia Group's study-based trial register until January 24, 2024.

Developing STEP-SE: A Qualitative Usability Study of a Novel Patient-Reported Outcomes Tool for Managing Side Effects in Shared Decision-Making for Schizophrenia Spectrum Disorder Care.

Background: Schizophrenia treatment with antipsychotics often results in side effects that impact adherence and quality of life. Managing these effects remains challenging, as it requires balancing efficacy and tolerability. The Schizophrenia Technological Evaluation of Patient Side Effects (STEP-SE) app aims to aid side effects monitoring and management through shared decision-making (SDM).

Effectiveness of pharmacological treatments for severe agitation in real-world emergency settings: protocol of individual-participant-data network meta-analysis.

Background: Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision.

Methods: We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings.

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data.

Background: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies.

Methods: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.

Non-invasive brain stimulation for treatment-resistant schizophrenia: protocol of a systematic review and network meta-analysis.

Background: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.

Psychological and psychosocial interventions for treatment-resistant schizophrenia: a systematic review and network meta-analysis.

Background: Many patients with schizophrenia have symptoms that do not respond to antipsychotics. This condition is called treatment-resistant schizophrenia and has not received specific attention as opposed to general schizophrenia. Psychological and psychosocial interventions as an add-on treatment to pharmacotherapy could be useful, but their role and comparative efficacy to each other and to standard care in this population are not known.

Single-arm meta-analysis of drug response in placebo-controlled versus active-controlled antipsychotic drug trials in schizophrenia.

Antipsychotic drug efficacy may vary in placebo-controlled and active-controlled trials. The study aims to investigate the performance of antipsychotics in these two different study designs using single-arm meta-analysis. We included randomized controlled trials (RCTs) comparing second-generation antipsychotics with placebo or other antipsychotics from our previous systematic reviews and updated the results with the search on Cochrane Schizophrenia Group register until March 06, 2022.

Sharing information across patient subgroups to draw conclusions from sparse treatment networks.

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 evaluation of the underlying NMA assumptions of transitivity and consistency.

Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies.

Background: There is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studies on the efficacy, safety, and underlying mechanism of action of TAAR1 agonism for psychosis.

Efficacy, acceptability and side-effects of oral versus long-acting- injectables antipsychotics: Systematic review and network meta-analysis.

Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI.

Understanding effect size: an international online survey among psychiatrists, psychologists, physicians from other medical specialities, dentists and other health professionals.

Background And Objective: Various ways exist to display the effectiveness of medical treatment options. This study examined various psychiatric, medical and allied professionals' understanding and perceived usefulness of eight effect size indices for presenting both dichotomous and continuous outcome data.

Methods: We surveyed 1316 participants from 13 countries using an online questionnaire.

Are the results of open randomised controlled trials comparing antipsychotic drugs in schizophrenia biased? Exploratory meta- and subgroup analysis.

A recent meta-epidemiological study did not reveal major differences between the results of blinded and open randomised-controlled trials (RCTs). Fewer patients may consent to double-blind RCTs than to open RCTs, compromising generalisability, making this question very important. However, the issue has not been addressed in schizophrenia.

Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis.

Background: There is no consensus on defining relapse in schizophrenia, and scale-derived criteria with unclear clinical relevance are widely used. We aimed to develop an evidence-based scale-derived set of criteria to define relapse in patients with schizophrenia or schizoaffective disorder.

Methods: We searched the Yale University Open Data Access (YODA) for randomised controlled trials (RCTs) in clinically stable adults with schizophrenia or schizoaffective disorder, and obtained individual participant data on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity (CGI-S), Personal and Social Performance (PSP), and Social and Occupational Functioning Assessment Scale (SOFAS).

Estimating and visualising the trade-off between benefits and harms on multiple clinical outcomes in network meta-analysis.

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 outcomes and individual preferences, such as the coverage area inside a spie chart, that, however, does not account for a trade-off between efficacy and safety outcomes.

Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis.

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 tolerability of pharmacological interventions for acute bipolar depression.