Positive and Negative Symptoms Changes in Schizophrenia Patients on Antipsychotic Treatment: a Systematic Review and Dose-Response Meta-analysis

29/08/2026

AI Summary

Most antipsychotics produce parallel dose-response curves for positive and negative symptoms, with smaller effects on negative symptoms in acutely exacerbated patients.
Partial dopamine agonists often show equal or greater effect sizes for negative symptoms compared with positive symptoms.
Dose-response curves generally decline to an inflection point then plateau or lose efficacy, informing clinical dosing and antipsychotic mechanism.

AI Summary

STUDY RESULTS: Finally, a total of 165 studies were identified. 112 studies with 385 dose arms (37 096 participants) reported positive or negative symptoms and were evaluated in meta-analyses.

Most antipsychotics showed parallel dose-response curves for positive and negative symptoms, with a smaller magnitude of effect on negative symptoms-except a few drugs, in particular partial dopamine agonists which had at least equal effect sizes for positive and negative symptoms.

CONCLUSIONS: The effects of antipsychotics on negative symptoms are smaller than those on positive symptoms, at least in studies of mostly acutely exacerbated patients.

Basic summary

Schizophr Bull. 2026 Aug 20;52(5):sbag077. doi: 10.1093/schbul/sbag077.

ABSTRACT

BACKGROUND AND HYPOTHESIS: Positive and negative symptoms are core features of schizophrenia and key indicators of antipsychotic efficacy. We aimed to explore the relationship between antipsychotic doses and changes in positive/negative symptoms.

STUDY DESIGN: We reviewed the Cochrane Schizophrenia Group register (updated on July-26-2024) and prior systematic reviews to identify fixed-dose randomized controlled trials that assessed the monotherapy effects of 21 antipsychotic drugs in acute schizophrenia. The primary outcome measure was the average change in positive and negative symptoms from the studies’ baseline to endpoint, calculated using standard mean differences as the effect size metric. Dose-response relationships were analyzed using random-effects meta-analyses with restricted cubic splines.

STUDY RESULTS: Finally, a total of 165 studies were identified. 112 studies with 385 dose arms (37 096 participants) reported positive or negative symptoms and were evaluated in meta-analyses. Most antipsychotics showed parallel dose-response curves for positive and negative symptoms, with a smaller magnitude of effect on negative symptoms-except a few drugs, in particular partial dopamine agonists which had at least equal effect sizes for positive and negative symptoms. In most cases both curves declined until reaching an inflection point, then plateaued or efficacy decreased.

CONCLUSIONS: The effects of antipsychotics on negative symptoms are smaller than those on positive symptoms, at least in studies of mostly acutely exacerbated patients. Nevertheless, the dose-response curves for both types of symptoms are relatively parallel. This information can assist clinicians in dosing antipsychotics and has implications for the understanding of the antipsychotic mechanism.

PMID:42667248 | DOI:10.1093/schbul/sbag077

Document this CPD