A review on side effect management of second-generation antipsychotics to treat schizophrenia: a drug safety perspective.

Introduction: Effective side effects management present a challenge in antipsychotic treatment with second-generation antipsychotics (SGAs). In recent years, most of the commonly used SGAs, except for clozapine, have been shown to differ only slightly in their effectiveness, but considerably regarding perceived side effects, safety profiles, and compatibility to preexisting medical conditions.

Areas Covered: The current state of available evidence on side-effect management in SGA treatment of patients with schizophrenia spectrum disorders (SSD) is reviewed.

Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data.

Background: There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence.

Vaccination and clozapine use: a systematic review and an analysis of the VAERS database.

In the context of COVID-19 concerns related to the potential interactions between clozapine and vaccination arose. With the ultimate goal of deriving recommendations for clinical practice, we systematically reviewed the current evidence regarding altered vaccine effectiveness in clozapine-treated patients and safety aspects of vaccination, such as haematological changes and the impact of vaccines on clozapine blood levels, in clozapine-treated patients. A systematic PRISMA-conform literature search of four databases (PubMed, PsycINFO, EMBASE and Cochrane Library) complemented by a case-by-case analysis of the Vaccine Adverse Event Reporting System (VAERS) database was performed.

The Direct and Long-Term Effects of Raloxifene as Adjunctive Treatment for Schizophrenia-Spectrum Disorders: A Double-Blind, Randomized Clinical Trial.

Background And Hypothesis: Several studies suggest that raloxifene, a selective estrogen receptor modulator, improves symptoms and cognition in post-menopausal women with Schizophrenia-Spectrum Disorders (SSD). We aimed to assess the effects of adjunctive raloxifene in women and men with SSD.

Study Design: This parallel, randomized, double-blind, placebo-controlled trial included adult SSD patients across the Netherlands and Belgium.

Barriers to genetic testing in clinical psychiatry and ways to overcome them: from clinicians' attitudes to sociocultural differences between patients across the globe.

Genetic testing has evolved rapidly over recent years and new developments have the potential to provide insights that could improve the ability to diagnose, treat, and prevent diseases. Information obtained through genetic testing has proven useful in other specialties, such as cardiology and oncology. Nonetheless, a range of barriers impedes techniques, such as whole-exome or whole-genome sequencing, pharmacogenomics, and polygenic risk scoring, from being implemented in psychiatric practice.

Genetic determinants associated with response to clozapine in schizophrenia: an umbrella review.

Objective: Clozapine response varies widely from person to person, which may be due to inter-individual genetic variability. This umbrella review aims to summarize the current evidence on associations between pharmacodynamic genes and response to clozapine treatment.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology, a systematic literature search was conducted in the PubMed and EMBASE databases from inception to November 2021 to identify systematic reviews and meta-analyses of studies that examined genetic determinants of clozapine response.

Event-related potentials and use of psychotropic medication in major psychiatric disorders.

Background: Attention deficits measured using event-related potentials (ERPs) have been frequently reported in several major psychiatric disorders, e.g. mood disorder (MD), psychotic disorder (PD) and substance use disorder (SUD).

Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach.

Purpose: Posttraumatic Stress Disorder (PTSD) is associated with increased alcohol use and alcohol use disorder (AUD), which are all moderately heritable. Studies suggest the genetic association between PTSD and alcohol use differs from that of PTSD and AUD, but further analysis is needed.

Basic Procedures: We used genomic Structural Equation Modeling (genomicSEM) to analyze summary statistics from large-scale genome-wide association studies (GWAS) of European Ancestry participants to investigate the genetic relationships between PTSD (both diagnosis and re-experiencing symptom severity) and a range of alcohol use and AUD phenotypes.

Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials.

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 efficacy-effectiveness gap.

Objective: To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals.

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness.

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported.

Stratified psychiatry: Tomorrow's precision psychiatry?

Here we review the paradigm-change from one-size-fits-all psychiatry to more personalized-psychiatry, where we distinguish between 'precision psychiatry' and 'stratified psychiatry'. Using examples in Depression and ADHD we argue that stratified psychiatry, using biomarkers to facilitate patients to best 'on-label' treatments, is a more realistic future for implementing biomarkers in clinical practice.

Comprehensive analyses of RNA-seq and genome-wide data point to enrichment of neuronal cell type subsets in neuropsychiatric disorders.

Neurological and psychiatric disorders, including substance use disorders, share a range of symptoms, which could be the result of shared genetic background. Many genetic loci have been identified for these disorders using genome-wide association studies, but conclusive evidence about cell types wherein these loci are active is lacking. We aimed to uncover implicated brain cell types in neuropsychiatric traits and to assess consistency in results across RNA datasets and methods.

Diphtheria And Tetanus Vaccination History Is Associated With Lower Odds of COVID-19 Hospitalization.

Background: COVID-19 is characterized by strikingly large, mostly unexplained, interindividual variation in symptom severity: while some individuals remain nearly asymptomatic, others suffer from severe respiratory failure. Previous vaccinations for other pathogens, in particular tetanus, may partly explain this variation, possibly by readying the immune system.

Methods: We made use of data on COVID-19 testing from 103,049 participants of the UK Biobank (mean age 71.

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity.

Background And Purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain.

Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders.

Genetic evidence for a large overlap and potential bidirectional causal effects between resilience and well-being.

Resilience and well-being are strongly related. People with higher levels of well-being are more resilient after stressful life events or trauma and vice versa. Less is known about the underlying sources of overlap and causality between the constructs.

The effect of prednisolone on symptom severity in schizophrenia: A placebo-controlled, randomized controlled trial.

Objective: Immune dysregulation may be involved in the pathophysiology of schizophrenia. Given the need for new treatment options in schizophrenia, anti-inflammatory medication could be a potential treatment in this illness.

Methods: In this double-blind, placebo-controlled clinical trial, patients with schizophrenia, schizoaffective disorder or psychosis NOS were randomized 1:1 to either prednisolone or placebo, in addition to their regular antipsychotic medication.

The genetic basis of major depression.

Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date.

Morbidity and mortality in schizophrenia with comorbid substance use disorders.

Objective: Schizophrenia is highly comorbid with substance use disorders (SUD) but large epidemiological cohorts exploring the prevalence and prognostic significance of SUD are lacking. Here, we investigated the prevalence of SUD in patients with schizophrenia in Finland and Sweden, and the effect of these co-occurring disorders on risks of psychiatric hospitalization and mortality.

Methods: 45,476 individuals with schizophrenia from two independent national cohort studies, aged <46 years at cohort entry, were followed during 22 (1996-2017, Finland) and 11 years (2006-2016, Sweden).

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301).

Raloxifene augmentation in men and women with a schizophrenia spectrum disorder: A study protocol.

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women.

Phenome-wide and genome-wide analyses of quality of life in schizophrenia.

Background: Schizophrenia negatively affects quality of life (QoL). A handful of variables from small studies have been reported to influence QoL in patients with schizophrenia, but a study comprehensively dissecting the genetic and non-genetic contributing factors to QoL in these patients is currently lacking.

Aims: We adopted a hypothesis-generating approach to assess the phenotypic and genotypic determinants of QoL in schizophrenia.

Isolated nausea and vomiting as the cardinal presenting symptoms of clozapine-induced myocarditis: a case report.

Background: Clozapine is an atypical antipsychotic proven to be superior in the treatment of treatment-resistant schizophrenia. Myocarditis is a rare, but well-known complication of treatment with clozapine. Only few cases have been reported in which nausea and vomiting were prominent symptoms.