QT and QTc in Male Patients with Psychotic Disorders Treated with Atypical Neuroleptics.
Ontology highlight
ABSTRACT:
SUBMITTER: Miniati M
PROVIDER: S-EPMC5529641 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Drug-induced QT prolongation is associated with higher risk of cardiac arrhythmias and cardiovascular mortality. We investigated the effects of atypical antipsychotic drugs on QT interval in children and adults with mental disorders.We conducted random-effects direct frequentist meta-analyses of aggregate data from randomized controlled trials (RCT) and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to October 2017 identified studies that examined aripiprazole, quetiapine, risperidone, olanzapine, ziprasidone and brexpiprazole.Low quality evidence suggests that aripiprazole (four meta-analyses and twelve RCTs), brexpiprazole (one systematic review and four RCTs) or olanzapine (five meta-analyses and twenty RCTs) do not increase QT interval. Low quality evidence suggests that ziprasidone (five meta-analyses and 11 RCTs) increases QT interval and the rates of QT prolongation while risperidone (four meta-analyses, 70 RCTs) and quetiapine (two meta-analyses and seven RCTs) are associated with QT prolongation and greater odds of torsades de pointes ventricular tachycardia especially in cases of drug overdose.The main conclusion of our study is that in people with mental disorders and under treatment with atypical antipsychotic drugs, in order to avoid QT prolongation and reduce the risk of ventricular tachycardia clinicians may recommend aripiprazole, brexpiprazole or olanzapine in licensed doses. Long-term comparative safety needs to be established.
| S-EPMC5952011 | biostudies-other
Project description:ImportancePsychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s.ObjectivesTo estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors.Design, setting, and participantsAn international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics.ExposuresAge, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area-level exposures.Main outcomes and measuresIncidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist.ResultsA total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95% CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95% CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95% CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95% CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95% CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95% CI, 0.2-0.5).Conclusions and relevanceThis study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses.
| S-EPMC5833538 | biostudies-literature
Project description:Absolute and relative risks of violence are increased in patients with psychotic disorders, but the contribution of triggers for violent acts to these risks is uncertain.To examine whether a range of triggers for violent acts are associated with risks of violence in patients diagnosed with psychotic disorders and in individuals without a psychiatric diagnosis.Using a sample of all individuals born in Sweden between 1958 and 1988 (N?=?3?123?724), we identified patients in the National Patient Register who were diagnosed with schizophrenia spectrum disorders (n?=?34?903) and bipolar disorder (n?=?29?692), as well as unaffected controls (n?=?2?763?012). We then identified, within each subsample, persons who had experienced any of the following triggers for violent acts between January 1, 2001, and December 15, 2013: exposure to violence, parental bereavement, self-harm, traumatic brain injury, unintentional injuries, and substance intoxication. By using within-individual models, we conducted conditional logistic regression to compare the risk of the individual engaging in violent acts in the week following the exposure to a trigger with the risk during earlier periods of equivalent length. All time-invariant confounders (eg, genetic and early environmental influences) were controlled for by this research design and we further adjusted for time-varying sociodemographic factors.Adjusted odds ratios (aORs) of violent crime occurring in the week following the exposure to a trigger event compared with earlier periods.Among the sample of 2?827?607 individuals (1?492?186 male and 1?335?421 female), all of the examined trigger events were associated with increased risk of violent crime in the week following exposure. The largest 1-week absolute risk of violent crime was observed following exposure to violence (70-177 violent crimes per 10?000 persons). For most triggers, the relative risks did not vary significantly by diagnosis, including unintentional injuries (aOR range, 3.5-4.8), self-harm (aOR range, 3.9-4.2), and substance intoxication (aOR range, 3.0-4.0). Differences by diagnosis included parental bereavement, which was significantly higher in patients with schizophrenia spectrum disorders (aOR, 5.0; 95% CI, 3.0-8.1) compared with controls (aOR, 1.7; 95% CI, 1.3-2.2).In addition to identifying risk factors for violence, clarifying the timing of the triggers may provide opportunities to improve risk assessment and management in individuals with psychotic disorders.
| S-EPMC5047356 | biostudies-other
Project description:Lack of insight, very frequent in schizophrenia, can be considered a deficit in Theory of Mind (ToM) performances, and is also found in other psychiatric disorders. In this study, we used the first- to third-person shift to examine subjects with psychotic and psychotic mood disorders. 92 patients were evaluated with SANS and SAPS scales and asked to talk about their delusions. They were asked to state whether they thought what they said was believable for them and for the interviewer. Two weeks later, 79 patients listened to a tape where their delusion was reenacted by two actors and were asked the same two questions. Some patients gained insight when using third-person perspective. These patients had lower SAPS scores, a lower score on SAPS item on delusions, and significant improvement in their SAPS delusion score at the second interview. Better insight was not related to a specific diagnostic group.
| S-EPMC3428617 | biostudies-other
Project description:OBJECTIVE:It has been shown that men with a longstanding psychotic disorder have worse clinical and functional outcomes than women. Our objectives were to examine whether these sex differences are also present among patients treated in an early intervention service (EIS) for psychosis and to determine if these differences are related to risk factors other than sex. METHOD:Patients (N = 569) were assessed for demographic/clinical characteristics at entry and for symptoms/functioning over 2 years of treatment. Clinical outcomes included remission of positive, negative, and total symptoms. Functional outcomes included good functioning and functional remission. Logistic regression models examined the relationship between sex and outcomes after 1 and 2 years of treatment while controlling for the influence of other risk factors. RESULTS:Men reported to be less educated and have a longer duration of untreated psychosis, poorer childhood and early adolescent premorbid functioning, higher rates of substance abuse/dependence disorders, greater severity of baseline negative symptoms, and poorer baseline social/occupational functioning than women. Women were more likely to achieve symptom remission than men after 2 years of treatment (negative odds ratio [OR], 1.69; 95% confidence interval [CI], 1.02 to 2.78; total OR, 1.79; 95% CI, 1.08 to 2.98). Women were also more likely than men to exhibit good functioning (OR, 1.61; 95% CI, 1.04 to 2.49) after 1 but not after 2 years of treatment. These results did not persist after controlling for other risk factors that could confound these associations (i.e., childhood premorbid functioning and age at onset of psychosis). CONCLUSIONS:Sex differences seen in outcomes among patients treated in an EIS for psychosis may be largely influenced by the disparity of other risk factors that exist between the 2 sexes.
| S-EPMC6783666 | biostudies-literature
Project description:Objective: The ACCESS treatment model offers assertive community treatment (ACT) embedded in an integrated care program to patients with severe psychotic disorders. Compared to standard care, it proved to be more effective in terms of service disengagement and other outcomes in patients with psychotic disorders over 12, 24, and 48 months. Many patients with severe mental disorders experience involuntary admissions which can be potentially traumatic. In this study, we assessed the effect of ACT on reducing involuntary admissions over an observation period of 4 years. Method: One hundred seventy-one patients treated in ACCESS were included in this study. The primary outcome was rate of involuntary admissions during 48 months. Secondary outcomes were differences between those with and without involuntary admissions in the 2 years prior to ACCESS regarding change of psychopathology, severity of illness, psychosocial functioning, quality of life, satisfaction with care, medication non-adherence, and service-disengagement. Results: Of 171 patients, 58 patients (33.9%) were involuntarily admitted to hospital in the past 2 years before entry. During the 4 years of treatment, 16 patients (9.4%) were involuntarily admitted to hospital which was a significantly lower rate compared to the 2 years before inclusion in ACCESS (p < .001). Comparing the two groups, larger improvements in severity of illness (p = .004) and functional status (p = .043) were detected in the group with no history of involuntary admissions. At 4-year follow-up, of the remaining patients, 69.2% (n = 81) were full adherent (p < .001), compared to 18.9% (n = 31) at baseline with no differences between the two groups over the study period (p = .25). Over 4 years, only 13 patients (13.2%) were service-disengaged due to non-practical reasons. Conclusions: In this long-term study, we were able to demonstrate a reduction in involuntary admissions in four treatment years compared to the 2 years prior to admission to the ACCESS model in patients with severe and mostly multiphase schizophrenia spectrum disorders and affective disorders with psychotic features. This may help prevent patients from suffering from a potentially traumatic experience during treatment in the psychiatric system. Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01888627.
| S-EPMC6822062 | biostudies-literature
Project description:A significant portion of patients with 22q11 deletion syndrome (22q11DS) develop psychiatric disorders, including schizophrenia and other psychotic and affective symptoms, and the responsible gene/s are assumed to also play a significant role in the etiology of nonsyndromic psychiatric disease. The most common psychiatric diagnosis among patients with 22q11DS is schizophrenia, thought to result from neurotransmitter imbalances and also from disturbed brain development. Several genes in the 22q11 region with known or suspected roles in neurotransmitter metabolism have been analyzed in patients with isolated schizophrenia; however, their contribution to the disease remains controversial. Haploinsufficiency of the TBX1 gene has been shown to be sufficient to cause the core physical malformations associated with 22q11DS in mice and humans and via abnormal brain development could contribute to 22q11DS-related and isolated psychiatric disease. 22q11DS populations also have increased rates of psychiatric conditions other than schizophrenia, including mood disorders. We therefore analyzed variations at the TBX1 locus in a cohort of 446 white patients with psychiatric disorders relevant to 22q11DS and 436 ethnically matched controls. The main diagnoses included schizophrenia (n = 226), schizoaffective disorder (n = 67), bipolar disorder (n = 82), and major depressive disorder (n = 29). We genotyped nine tag SNPs in this sample but did not observe significant differences in allele or haplotype frequencies in any of the analyzed groups (all affected, schizophrenia and schizoaffective disorder, schizophrenia alone, and bipolar disorder and major depressive disorder) compared with the control group. Based on these results we conclude that TBX1 variation does not make a strong contribution to the genetic etiology of nonsyndromic forms of psychiatric disorders commonly seen in patients with 22q11DS.
| S-EPMC1952674 | biostudies-literature
Project description:Diagnosis of Parkinson' disease (PD) carries a high misdiagnosis rate due to failure to recognize atypical parkinsonian disorders (APD). Usually by the time of diagnosis greater than 60% of the neurons in the substantia nigra are dead. Therefore, early detection would be beneficial so that therapeutic intervention may be initiated early in the disease process. We used splice variant-specific microarrays to identify mRNAs whose expression is altered in peripheral blood of early-stage PD patients compared to healthy and neurodegenerative disease controls. Quantitative polymerase chain reaction assays were used to validate splice variant transcripts in independent sample sets. Here we report a PD signature used to classify blinded samples with 90% sensitivity and 94% specificity and an APD signature that resulted in a diagnosis with 95% sensitivity and 94% specificity. This study provides the first discriminant functions with coherent diagnostic signatures for PD and APD. Analysis of the PD biomarkers identified a regulatory network with nodes centered on the transcription factors HNF4A and TNF, which have been implicated in insulin regulation.
| S-EPMC3428307 | biostudies-literature
Project description:BackgroundWorking memory (WM) has been a central focus of cognitive neuroscience research because WM is a resource that is involved in many different cognitive operations. The goal of this study was to evaluate the clinical utility of WM paradigms developed in the basic cognitive neuroscience literature, including methods designed to estimate storage capacity without contamination by lapses of attention.MethodsA total of 61 people with schizophrenia, 49 with schizoaffective disorder, 47 with bipolar disorder with psychosis, and 59 healthy volunteers were recruited. Participants received multiple WM tasks, including two versions each of a multiple Change Detection paradigm, a visual Change Localization paradigm, and a Running Span task.ResultsHealthy volunteers performed better than the combined patient group on the visual Change Localization and running span measures. The multiple Change Detection tasks provided mixed evidence about WM capacity reduction in the patient groups, but a mathematical model of performance suggested that the patient groups differed from controls in their rate of attention lapsing. The 3 patient groups performed similarly on the WM tasks. Capacity estimates from the Change Detection and Localization tasks showed significant correlations with functional capacity and functional outcome.ConclusionsThe patient groups generally performed in a similarly impaired fashion across tasks, suggesting that WM impairment and attention lapsing are general features of psychotic disorders. Capacity estimates from the Change Localization and Detection tasks were related to functional capacity and outcome, suggesting that these methods may be useful in a clinical context.
| S-EPMC6581132 | biostudies-literature
Project description:Epigenetics is the study of chromatin-the physical material that forms chromosomes, composed of DNA wound around specialized histone proteins-and of how the modification of chromatin acts to establish stable states of gene expression in a cell-specific manner. Chromatin is regulated through three mechanisms: DNA methylation, histone modification, and RNA interference. These basic biological processes form the molecular interface between the genome and the environment, contributing to the regulation of gene expression in health and disease. Investigation of epigenetic mechanisms is yielding exciting insights in many areas of medicine, and a large and rapidly growing literature describes epigenetics as central to many aspects of the pathophysiology of psychotic disorders. This article first discusses speculative points as to why the mechanisms of epigenetics may be satisfying explanatory mechanisms in the etiology of psychotic disorders, then details emerging experimental evidence of roles for the three types of epigenetic mechanisms in these illnesses, and finally discusses these mechanisms as potentially compelling areas of research for the development of future treatments.
| S-EPMC5547575 | biostudies-other