Negative Symptom Interventions in Youth at Risk of Psychosis: A Systematic Review and Network Meta-analysis

Abstract

Objective: Youth at clinical high risk (CHR) for psychosis often demonstrate significant negative symptoms, which have been reported to be predictive of conversion to psychosis and a reduced quality of life but treatment options for negative symptoms remain inadequate. Therefore, we conducted a systematic review and network meta-analysis of all intervention studies examining negative symptom outcomes in youth at CHR for psychosis.

Method: The authors searched PsycINFO, Medline, Embase, CINAHL, and EBM from inception to December 2016. Studies were selected if they included any intervention that reported follow-up negative symptoms in youth at CHR for psychosis. Treatment comparisons were evaluated using both pairwise and network meta-analyses. Due to the differences in negative symptom scales the effect sizes were reported as the standardized mean difference (SMD).

Results: Of 3027 citations, 32 studies met our inclusion criteria, including a total of 2463 CHR participants. The null hypothesis was not rejected for any of the 11 treatments. N-methyl-D-aspartate-receptor (NMDAR) modulators trended toward a significant reduction in negative symptoms compared to placebo (SMD = -0.54; 95% CI = -1.09 to 0.02; I2 = 0%, P = .06). In respective order of descending effectiveness as per the treatment hierarchy, NMDAR modulators were more effective than family therapy, need-based interventions, risperidone, amisulpride, cognitive behavioral therapy, omega-3, olanzapine, supportive therapy, and integrated psychological interventions.

Conclusions: Efficacy and effectiveness were not confirmed for any negative symptom treatment. Many studies had small samples and the majority were not designed to target negative symptoms.

Fig. 1.

PRISMA flow diagram of systematic search and included studies.

Fig. 2.

(A) Risk of bias graph for RCTs: review authors’ judgments about each risk of bias item presented as percentages across all included studies. (B) Risk of bias summary: review author’s judgments about each risk of bias item for each included study.

Fig. 3.

Plot of the negative symptom network. Nodes are weighted according to the number of studies including the respective interventions. Edges are weighted according to the number of studies including either that treatment or that comparison. Colored edges(green = low risk, yellow = unclear risk, red = high risk) according to risk of bias for blinding of outcome assessments, estimated as the level of bias in the majority of the trials and weighted according to the number of studies in each comparison.

Fig. 4.

Forest plot of the network meta-analysis. PLA, placebo; RIS, risperidone; OLA, olanzapine; NMD, N-methyl-d-aspartate receptor modulators; OME, omega-3; NBI, need-based interventions; AMI, amisulpride; CBT, cognitive behavioral therapy; SUP, supportive therapy; IPI, integrated psychological interventions; FAM, family therapy.