Proton Magnetic Resonance Spectroscopy and Illness Stage in Schizophrenia-A Systematic Review and Meta-Analysis

Background It is not known whether regional brain N-acetyl aspartate (NAA) changes in the progression from prodrome to chronic schizophrenia. We used effect size meta-analysis to determine which brain regions show the most robust reductions in NAA first episode and chronic schizophrenia as measured by proton magnetic resonance spectroscopy and to determine whether these changes are present in individuals at high risk of developing schizophrenia. Methods We identified 131 articles, of which 97 met inclusion criteria. Data were separated by stage of illness (at risk, first episode schizophrenia, chronic schizophrenia) and by brain region. For each region, mean and SD of the NAA measure was extracted. Results Significant reductions in NAA levels were found in frontal lobe, temporal lobe, and thalamus in both patient groups (effect size > .3; p < .01). In individuals at high risk of schizophrenia (of whom approximately 20% would be expected to undergo transition to psychosis), significant NAA reductions were present in thalamus (effect size = .78; p < .05), with reductions at trend level only in temporal lobe (effect size = .32; p < .1), and no reductions in frontal lobe (effect size = .05; p = .5). Conclusions These data suggest that schizophrenia is associated with loss of neuronal integrity in frontal and temporal cortices and in the thalamus and suggest that these changes in the frontal and temporal lobe might occur in the transition between the at-risk phase and the first episode

How effective are common medications: a perspective based on meta-analyses of major drugs

Study protocol. (PDF 161 kb

Associations between individual antipsychotics and the risk of arrests and convictions of violent and other crime : a nationwide within-individual study of 74925 persons

Background Individuals diagnosed with psychiatric disorders who are prescribed antipsycho-tics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes. Method We identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclo-penthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, ris-peridone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications. Results The relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50-0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28-0.44), olanzapine (aRRs: 0.46-0.72), and risperidone (aRRs: 0.53-0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68-0.84) and haloperidol (aRRs: 0.67-0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33-0.69). Conclusions There is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes.Peer reviewe

Remission in schizophrenia: validity, frequency, predictors, and patients' perspective 5 years later

In March 2005, the Remission in Schizophrenia Working Group (RSWG) proposed a consensus definition of symptomatic remission in schizophrenia and developed specific operational criteria for its assessment. They pointed out, however, that the validity and the relationship to other outcome dimensions required further examination. This article reviews studies on the validity, frequency, and predictors of symptomatic remission in schizophrenia and studies on patients' perspectives. These studies have demonstrated that the RSWG remission criteria appear achievable and sustainable for a significant proportion of patients, and are related to a better overall symptomatic status and functional outcome and, to a less clear extent, to a better quality of life and cognitive performance. However, achieving symptomatic remission is not automatically concurrent with an adequate status in other outcome dimensions. The results of the present review suggest that the RSWG remission criteria are valid and useful. As such, they should be consistently applied in clinical trials. However, the lack of consensus definitions of functional remission and adequate quality of life hampers research on their predictive validity on these outcome dimensions. Future research should therefore search for criteria of these dimensions and test whether the RSWG remission criteria consistently predict a “good” outcome with respect to functioning and quality of life

Crossroads of methodological choices in research synthesis: insights from two network meta-analyses on preventing relapse in schizophrenia

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 choices based on their clinical and research experience, with possible advantages and shortcomings. In this contribution, we will critically assess two network meta-analyses on the topic of pharmacological prevention of relapse in schizophrenia, carried out by two different research groups. We will highlight the implications of different methodological choices on the analysis results and their clinical-epidemiological interpretation. Moreover, we will discuss some of the most relevant technical issues of network meta-analyses for which there is not a broad methodological agreement, including the assessment of transitivity

The Prevalence of Mental Illness in Homeless People in Germany

BACKGROUND The number of homeless people in Germany is increasing. Studies from multiple countries have shown that most homeless people suffer from mental illnesses that require treatment. Accurate figures on the prevalence of mental illness among the homeless in Germany can help improve care structures for this vulnerable group. METHODS We carried out a systematic review and meta-analysis on the prevalence of mental illness among homeless people in Germany. RESULTS 11 pertinent studies published from 1995 to 2013 were identified. The overall study population consisted of 1220 homeless people. The pooled prevalence of axis I disorders was 77.4%, with a 95% confidence interval [95% CI] of [71.3; 82.9]. Substance-related disorders were the most common type of disorder, with a pooled prevalence of 60.9% [53.1; 68.5]. The most common among these was alcoholism, with a prevalence of 55.4% [49.2; 61.5]. There was marked heterogeneity across studies. CONCLUSION In Germany, the rate of mental illness requiring treatment is higher among the homeless than in the general population. The development and implementation of suitable care models for this marginalized and vulnerable group is essential if their elevated morbidity and mortality are to be reduced

Should We Treat Depression with drugs or psychological interventions? A Reply to Ioannidis

We reply to the Ioannidis's paper "Effectiveness of antidepressants; an evidence based myth constructed from a thousand controlled trials." We disagree that antidepressants have no greater efficacy than placebo. We present the efficacy from hundreds of trials in terms of the percentage of patients with a substantial clinical response (a 50% improvement or more symptomatic reduction). This meta-analysis finds that 42-70% of depressed patients improve with drug and 21%-39% improve with placebo. The response benefit of antidepressant treatment is 33%-11% greater than placebo. Ioannidis argues that it would be vanishingly smaller because systematic biasing in these clinical trials would reduce the drug-placebo difference to zero. Ioannidis' argument that antidepressants have no benefit is eroded by his failures of logic because he does not present any evidence that there are a large number of studies where placebo is substantially more effective than drug. (To reduce to zero, one would also have to show that some of the unpublished studies find placebo better than drug and have substantial systematic or methodological bias). We also present the empirical evidence showing that these methodological concerns generally have the opposite effect of what Ioannidis argues, supporting our contention that the measured efficacy of antidepressants likely underestimates true efficacy

Imputing the Number of Responders from the Mean and Standard Deviation of CGI-Improvement in Clinical Trials Investigating Medications for Autism Spectrum Disorder

Introduction: Response to treatment, according to Clinical Global Impression-Improvement (CGI-I) scale, is an easily interpretable outcome in clinical trials of autism spectrum disorder (ASD). Yet, the CGI-I rating is sometimes reported as a continuous outcome, and converting it to dichotomous would allow meta-analysis to incorporate more evidence. Methods: Clinical trials investigating medications for ASD and presenting both dichotomous and continuous CGI-I data were included. The number of patients with at least much improvement (CGI-I ≤ 2) were imputed from the CGI-I scale, assuming an underlying normal distribution of a latent continuous score using a primary threshold θ = 2.5 instead of θ = 2, which is the original cut-off in the CGI-I scale. The original and imputed values were used to calculate responder rates and odds ratios. The performance of the imputation method was investigated with a concordance correlation coefficient (CCC), linear regression, Bland–Altman plots, and subgroup differences of summary estimates obtained from random-effects meta-analysis. Results: Data from 27 studies, 58 arms, and 1428 participants were used. The imputation method using the primary threshold (θ = 2.5) had good performance for the responder rates (CCC = 0.93 95% confidence intervals [0.86, 0.96]; β of linear regression = 1.04 [0.95, 1.13]; bias and limits of agreements = 4.32% [−8.1%, 16.74%]; no subgroup differences χ(2) = 1.24, p-value = 0.266) and odds ratios (CCC = 0.91 [0.86, 0.96]; β = 0.96 [0.78, 1.14]; bias = 0.09 [−0.87, 1.04]; χ(2) = 0.02, p-value = 0.894). The imputation method had poorer performance when the secondary threshold (θ = 2) was used. Discussion: Assuming a normal distribution of the CGI-I scale, the number of responders could be imputed from the mean and standard deviation and used in meta-analysis. Due to the wide limits of agreement of the imputation method, sensitivity analysis excluding studies with imputed values should be performed