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

Schizophr Bull. 2018 Jun 6;44(4):807-823. doi: 10.1093/schbul/sbx139.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Female
  • Humans
  • Male
  • Network Meta-Analysis*
  • Outcome Assessment, Health Care / statistics & numerical data*
  • Psychotherapy / statistics & numerical data*
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / physiopathology
  • Psychotic Disorders / therapy*
  • Schizophrenia / drug therapy
  • Schizophrenia / physiopathology
  • Schizophrenia / therapy*
  • Young Adult


  • Antipsychotic Agents