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

ABSTRACT: 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.

SUBMITTER: Wagner E

PROVIDER: S-EPMC8458455 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe last comprehensive systematic review of the incidence of psychotic disorders was published in 2004. New epidemiological data from different settings now permit a broader understanding of global variation. We examined the variation in psychosis by demographic characteristics and study method.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, PsycINFO, and bibliographies, and directly contacted first authors. We sought to obtain citations of original research published between Jan 1, 2002, and Dec 31, 2017, on incidence of non-organic adult-onset psychotic disorder. We included papers that were published or in grey literature and had no language restrictions. Data were extracted from published reports, where possible, by sex, age, and ethnic group. Quality of yield was assessed. Data were assessed using univariable random-effects meta-analysis and meta-regression. We registered our systematic review on PROSPERO, number CRD42018086800.FindingsFrom 56 721 records identified, 177 met inclusion criteria. The pooled incidence of all psychotic disorders was 26·6 per 100 000 person-years (95% CI 22·0-31·7). Heterogeneity was high (I2≥98·5%). Men were at higher risk of all psychotic disorders (incidence rate ratio 1·44 [1·27-1·62]) and non-affective disorders (1·60 [1·44-1·77]) than women, but not affective psychotic disorders (0·87 [0·75-1·00]). Ethnic minorities were also at excess risk of all psychotic disorders (1·75 [1·53-2·00]), including non-affective disorders (1·71 [1·40-2·09]). Meta-regression revealed that population registers reported higher rates of non-affective disorders (9·64 [2·72-31·82]), schizophrenia (2·51 [1·24-5·21]), and bipolar disorder (4·53 [2·41-8·51]) than first contact study designs.InterpretationWe found marked variation in incidence of psychotic disorders by personal characteristics and place. Some geographical variation could be partially explained by differences in case ascertainment methods.FundingNone.

Project description:Vancomycin and teicoplanin are the glycopeptides currently in use for the treatment of infections caused by invasive beta-lactam-resistant gram-positive organisms. We conducted a systematic review and meta-analysis of randomized controlled trials that have compared vancomycin and teicoplanin administered systemically for the treatment of suspected or proven infections. A comprehensive search of trials without year, language, or publication status restrictions was performed. The primary outcome was all-cause mortality. Two reviewers independently extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled by using the fixed-effect model (RRs of >1 favor vancomycin). Twenty-four trials were included. All-cause mortality was similar overall (RR, 0.95; 95% CI, 0.74 to 1.21), and there was no significant heterogeneity. In trials that used adequate allocation concealment, the results favored teicoplanin (RR, 0.82; 95% CI, 0.63 to 1.06), while in trials with unknown methods or inadequate concealment, the results favored vancomycin (RR, 3.61; 95% CI, 1.27 to 10.30). The latter trials might have recruited more severely ill patients. No other variable affected the RRs for mortality, including the assessment of glycopeptides administered empirically or for proven infections, neutropenia, the participant's age, and drug dosing. There were no significant differences between teicoplanin and vancomycin with regard to clinical failure (RR, 0.92; 95% CI, 0.81 to 1.05), microbiological failure (RR, 1.24; 95% CI, 0.93 to 1.65), and other efficacy outcomes. Lower RRs (in favor of teicoplanin) for clinical failure were observed with a lower risk of bias and when treatment was initiated for infections caused by gram-positive organisms rather than empirically. Total adverse events (RR, 0.61; 95% CI, 0.50 to 0.74), nephrotoxicity (RR, 0.44; 95% CI, 0.32 to 0.61), and red man syndrome were significantly less frequent with teicoplanin. Teicoplanin is not inferior to vancomycin with regard to efficacy and is associated with a lower adverse event rate than vancomycin.

Project description:ObjectivesThe purpose of this study is to provide an updated systematic review to identify studies describing the prevalence of psychosis in order to explore methodological factors that could account for the variation in prevalence estimates.MethodsStudies with original data related to the prevalence of psychosis (published between 1990 and 2015) were identified via searching electronic databases and reviewing manual citations. Prevalence estimates were sorted according to prevalence type (point, 12-months and lifetime). The independent association between key methodological variables and the mean effect of prevalence was examined (prevalence type, case-finding setting, method of confirming diagnosis, international classification of diseases, diagnosis category, and study quality) by meta-analytical techniques and random-effects meta-regression.ResultsSeventy-three primary studies were included, providing a total of 101 estimates of prevalence rates of psychosis. Across these studies, the pooled median point and 12-month prevalence for persons was 3.89 and 4.03 per 1000 respectively; and the median lifetime prevalence was 7.49 per 1000. The result of the random-effects meta-regression analysis revealed a significant effect for the prevalence type, with higher rates of lifetime prevalence than 12-month prevalence (p<0.001). Studies conducted in the general population presented higher prevalence rates than those carried out in populations attended in health/social services (p = 0.006). Compared to the diagnosis of schizophrenia only, prevalence rates were higher in the probable psychotic disorder (p = 0.022) and non-affective psychosis (p = 0.009). Finally, a higher study quality is associated with a lower estimated prevalence of psychotic disorders (p<0.001).ConclusionsThis systematic review provides a comprehensive comparison of methodologies used in studies of the prevalence of psychosis, which can provide insightful information for future epidemiological studies in adopting the most relevant methodological approach.

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

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