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

Abstract

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.