Efficacy and Acceptability of Interventions for Attenuated Positive Psychotic Symptoms in Individuals at Clinical High Risk of Psychosis: A Network Meta-Analysis

Background: Attenuated positive psychotic symptoms represent the defining features of the clinical high-risk for psychosis (CHR-P) criteria. The effectiveness of each available treatment for reducing attenuated positive psychotic symptoms remains undetermined. This network meta-analysis (NMA) investigates the consistency and magnitude of the effects of treatments on attenuated positive psychotic symptoms in CHR-P individuals, weighting the findings for acceptability. Methods: Web of Science (MEDLINE), PsycInfo, CENTRAL and unpublished/gray literature were searched up to July 18, 2017. Randomized controlled trials in CHR-P individuals, comparing at least two interventions and reporting on attenuated positive psychotic symptoms at follow-up were included, following PRISMA guidelines. The primary outcome (efficacy) was level of attenuated positive psychotic symptoms at 6 and 12 months; effect sizes reported as standardized mean difference (SMD) and 95% CIs in mean follow-up scores between two compared interventions. The secondary outcome was treatment acceptability [reported as odds ratio (OR)]. NMAs were conducted for both primary and secondary outcomes. Treatments were cluster-ranked by surface under the cumulative ranking curve values for efficacy and acceptability. Assessments of biases, assumptions, sensitivity analyses and complementary pairwise meta-analyses for the primary outcome were also conducted. Results: Overall, 1,707 patients from 14 studies (57% male, mean age = 20) were included, representing the largest evidence synthesis of the effect of preventive treatments on attenuated positive psychotic symptoms to date. In the NMA for efficacy, ziprasidone + Needs-Based Intervention (NBI) was found to be superior to NBI (SMD = -1.10, 95% CI -2.04 to -0.15), Cognitive Behavioral Therapy-French and Morrison protocol (CBT-F) + NBI (SMD = -1.03, 95% CI -2.05 to -0.01), and risperidone + CBT-F + NBI (SMD = -1.18, 95% CI -2.29 to -0.07) at 6 months. However, these findings did not survive sensitivity analyses. For acceptability, aripiprazole + NBI was significantly more acceptable than olanzapine + NBI (OR = 3.73; 95% CI 1.01 to 13.81) at 12 months only. No further significant NMA effects were observed at 6 or 12 months. The results were not affected by inconsistency or evident small-study effects, but only two studies had an overall low risk of bias. Conclusion: On the basis of the current literature, there is no robust evidence to favor any specific intervention for improving attenuated positive psychotic symptoms in CHR-P individuals.