Antipsychotics, dopamine D₂ receptor occupancy and clinical improvement in schizophrenia: a meta-analysis

Abstract

Objective Treatment of schizophrenia (SCZ) was revolutionized with the development of the antipsychotic medications. Although imaging studies have linked antipsychotic D₂ receptor occupancy and clinical response in SCZ, heterogeneity between cohorts and methods has made it challenging to generalize findings across studies. The main objective of this meta-analysis was to analyze the relationship between in vivo estimation of typical and atypical antipsychotic D₂ receptor occupancy and treatment response in SCZ.Methods Using the keywords "dopamine D₂ receptor occupancy," "schizophrenia," "PET/SPECT" and "antipsychotics," and further refining our search to journal articles with information on % striatal D₂ occupancy and % change in clinical symptoms as indexed by either the BPRS or the PANSS, our final analysis consisted of 16 imaging studies (20 cohorts; N=206).Results The first step of the meta-analysis confirmed the positive relationship between antipsychotic medication and clinical improvement in SCZ (ES=1.36; 95% CI: 1.13-1.60). The second step of our analysis revealed that when D₂ occupancy was limited to less than 80% in order to control for the appearance of extrapyramidal symptoms, high D₂ occupancy was correlated with reduction in clinical scores (r=0.4, p<0.001) for medications other than clozapine or quetiapine.Conclusions Our results suggest that D₂ occupancy is a contributing factor for the mechanism of antipsychotic effect in SCZ for some but not all antipsychotic medications.