Do negative symptoms of schizophrenia change over time? A meta-analysis of longitudinal data

Negative symptoms are a core component of schizophrenia which can severely impact quality of life and functional outcomes. These symptoms are understood to be highly stable but this has not been tested in a meta-analysis, despite the wealth of longitudinal data available.

A systematic review of the literature was conducted, with eligible studies pooled into a random-effects meta-analysis. Planned meta-regressions were conducted to evaluate the impact of factors known to induce secondary negative symptoms, in addition to other possible sources of heterogeneity.

The main analysis included 89 samples from 41 studies, totalling 5944 participants. Negative symptoms were found to significantly reduce in all treatment interventions, including in placebo and treatment as usual conditions, with a medium effect size (ES) present across all study conditions (ES = 0.66, 95% confidence interval 0.56-0.77, I(2) = 94.0%). In a multivariate meta-regression, only the type of scale used was found to significantly influence negative symptom change. No difference in outcome was found between studies that excluded patients with a high level of positive or depressive symptoms, compared to those that did not.

Negative symptoms were found to reduce in almost all schizophrenia outpatient samples. A reduction was found across all conditions, with effect sizes ranging from small to large depending upon the condition type. These findings challenge the convention that negative symptoms are highly stable and suggest that they may improve to a greater extent than what has previously been assumed.