Effects of psychological treatments on functioning in people with Schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

Functioning is recognized as a key treatment goal in alleviating the burden of schizophrenia. Psychological interventions can play an important role in improving functioning in this population, but the evidence on their efficacy is limited. We therefore aimed to evaluate the effect of psychological interventions in functioning for patients with schizophrenia. To conduct this systematic review and meta-analysis, we searched for published and unpublished randomized controlled trials (RCTs) in EMBASE, MEDLINE, PsycINFO, BIOSIS, Cochrane Library, WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and the Study register of the Cochrane Schizophrenia Group. The outcome functioning was measured with validated scales. We performed random-effects pairwise meta-analysis to calculate standardized mean differences (SMDs) with 95% confidence intervals (CIs). We included 58 RCTs (5048 participants). Psychological interventions analyzed together (SMD = - 0.37, 95% CI - 0.49 to - 0.25), cognitive behavioral therapy (30 RCTs, SMD = - 0.26, 95% CI - 0.39 to - 0.12), and third wave cognitive-behavioral therapies (15 RCTs, SMD = - 0.60, 95% CI - 0.83 to - 0.37) were superior to control in improving functioning, while creative therapies (8 RCTs, SMD = 0.01, 95% CI - 0.38 to 0.39), integrated therapies (4 RCTs, SMD = - 0.21, 95% CI - 1.20 to 0.78) and other therapies (4 RCTs, SMD = - 0.74, 95% CI - 1.52 to 0.04) did not show a benefit. Psychological interventions, in particular cognitive behavioral therapy and third wave cognitive behavioral therapies, have shown a therapeutic effect on functioning. The confidence in the estimate was evaluated as very low due to risk of bias, heterogeneity and possible publication bias.

Are Randomized Controlled Trials on Pharmacotherapy and Psychotherapy for Positive Symptoms of Schizophrenia Comparable? A Systematic Review of Patient and Study Characteristics.

BACKGROUND: We examined patient and study characteristics of pharmacotherapy and psychotherapy trials to establish whether the effects of these 2 treatment strategies can be compared meaningfully. METHODS: We inspected all randomized controlled trials included in 2 recent meta-analyses on antipsychotics and psychotherapy in patients with positive symptoms of schizophrenia, searching EMBASE, MEDLINE, PsycINFO, Cochrane Library, and ClinicalTrials.gov. Differences between psychotherapy and pharmacotherapy trials were analyzed with Wilcoxon-Mann-Whitney and chi-square tests. RESULTS: Eighty studies with 18 271 participants on antipsychotic drugs and 53 studies with 4068 participants on psychotherapy were included. Psychotherapy studies included less severely ill patients (P < .0001), with a shorter duration of illness (P = .021), lasted for a longer period (P < .0001), administered the intervention as add-on to antipsychotics (P < .0001), had higher risk of bias in some domains including blinding of outcome assessment (P < .0001), and were funded publicly more frequently (P < .0001). Antipsychotic trials had larger sample sizes (P < .0001) and more study centers (P < .0001), included more males (P = .0001), inpatients (P < .0001), and slightly older patients (P = .031), more often used diagnostic operationalized criteria (P = .006), and were sponsored by pharmaceutical companies. They did not differ in conflict of interest (P = .24). CONCLUSIONS: We found key differences between the 2 groups of studies that encompass higher risk of bias in psychotherapy studies and the inclusion of more severe patients in drug trials. These differences imply that study and patient characteristics should be carefully taken into account before considering a network meta-analysis. In the interest of patients, psychopharmacologists and psychotherapists should optimize their treatments rather than seeing them in competition.

Response rates in patients with schizophrenia and positive symptoms receiving cognitive behavioural therapy: a systematic review and single-group meta-analysis.

BACKGROUND: Cognitive behavioural therapy has been used for schizophrenia, but to which extent it is effective is still controversial. Results of existing meta-analyses are of difficult interpretation, because they mainly present effect sizes in the form of standardized mean differences between intervention and control groups based on rating scales, which are of unclear clinical meaning. No meta-analysis has considered the number of patients responding to treatment yet. Based on this ground, we present the first meta-analysis examining the response rates of patients with schizophrenia and positive symptoms to cognitive behavioural therapy. METHODS: We searched multiple databases for randomized controlled trials on psychological interventions of schizophrenia including patients with positive symptoms, and included for this analysis the studies on cognitive behavioural therapy (last search: January 2018). We applied a validated imputation method to calculate the number of responders from rating scales for the outcomes overall symptoms and positive symptoms, based on two criteria, at least 20% and at least 50% reduction from baseline on PANSS or BPRS total scores. Data were pooled in a single-group summary meta-analysis using R software. Additionally, several potential moderators of response to cognitive behavioural therapy were examined by subgroup and meta-regression analyses. The protocol has been registered in PROSPERO (CRD42017067795). RESULTS: We included 33 studies with a total of 1142 participants receiving cognitive behavioural therapy. On average, 44.5 and 13.2% of the patients reached a 20% (minimally improved) and 50% (much improved) reduction of overall symptoms. Similarly, 52.9 and 24.8% of the patients reached a 20%/50% reduction of positive symptoms. Subgroup and meta-regression analyses revealed a better treatment response in overall symptoms for patients that were not treatment resistant and in studies with researchers' allegiance. Of borderline significance was the better response in studies employing expert therapists and in patients that were more severely ill at baseline. Blinding of outcome assessor, number of sessions, treatment duration, age and gender were not significant moderators of response. CONCLUSIONS: Our findings suggest that adding cognitive behavioural therapy to pharmacotherapy brings about a minimal improvement in overall symptoms among 44.5% of its recipients. Several study and patients characteristics can moderate response rates.

Psychological interventions to reduce positive symptoms in schizophrenia: systematic review and network meta-analysis.

Psychological treatments are increasingly regarded as useful interventions for schizophrenia. However, a comprehensive evaluation of the available evidence is lacking and the benefit of psychological interventions for patients with current positive symptoms is still debated. The present study aimed to evaluate the efficacy, acceptability and tolerability of psychological treatments for positive symptoms of schizophrenia by applying a network meta-analysis approach, that can integrate direct and indirect comparisons. We searched EMBASE, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Library, World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov for randomized controlled trials of psychological treatments for positive symptoms of schizophrenia, published up to January 10, 2018. We included studies on adults with a diagnosis of schizophrenia or a related disorder presenting positive symptoms. The primary outcome was change in positive symptoms measured with validated rating scales. We included 53 randomized controlled trials of seven psychological interventions, for a total of 4,068 participants receiving the psychological treatment as add-on to antipsychotics. On average, patients were moderately ill at baseline. The network meta-analysis showed that cognitive behavioural therapy (40 studies) reduced positive symptoms more than inactive control (standardized mean difference, SMD=-0.29; 95% CI: -0.55 to -0.03), treatment as usual (SMD=-0.30; 95% CI: -0.45 to -0.14) and supportive therapy (SMD=-0.47; 95% CI: -0.91 to -0.03). Cognitive behavioural therapy was associated with a higher dropout rate compared with treatment as usual (risk ratio, RR=0.74; 95% CI: 0.58 to 0.95). Confidence in the estimates ranged from moderate to very low. The other treatments contributed to the network with a lower number of studies. Results were overall consistent in sensitivity analyses controlling for several factors, including the role of researchers' allegiance and blinding of outcome assessor. Cognitive behavior therapy seems to be effective on positive symptoms in moderately ill patients with schizophrenia, with effect sizes in the lower to medium range, depending on the control condition.

Psychological interventions for positive symptoms in schizophrenia: protocol for a network meta-analysis of randomised controlled trials.

INTRODUCTION: There is rising awareness that we need multidisciplinary approaches integrating psychological treatments for schizophrenia, but a comprehensive evidence based on their relative efficacy is lacking. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs) to rank psychological treatments for schizophrenia according to their efficacy, acceptability and tolerability. METHODS AND ANALYSIS: We will include all RCTs comparing a psychological treatment aimed at positive symptoms of schizophrenia with another psychological intervention or with a no treatment condition (waiting-list and treatment as usual). We will include studies on adult patients with schizophrenia, excluding specific subpopulations (eg, first-episode patients or patients with psychiatric comorbidities). Primary outcome will be the change in positive symptoms on a published rating scale. Secondary outcomes will be acceptability (dropout), change in overall and negative symptoms of schizophrenia, response, relapse, adherence, depression, quality of life, functioning and adverse events. Published and unpublished studies will be sought through database searches, trial registries and websites. Study selection and data extraction will be conducted by at least two independent reviewers. We will conduct random-effects NMA to synthesise all evidences for each outcome and obtain a comprehensive ranking of all treatments. NMA will be conducted in Stata and R within a frequentist framework. The risk of bias in studies will be evaluated using the Cochrane Risk of Bias tool and the credibility of the evidence will be evaluated using an adaptation of the Grading of Recommendations Assessment, Development and Evaluation framework to NMA, recommended by the Cochrane guidance. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. ETHICS AND DISSEMINATION: No ethical issues are foreseen. Results from this study will be published in peer-reviewed journals and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42017067795.