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

Abstract

ObjectiveTreatment 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. MethodsUsing 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). ResultsThe 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. ConclusionsOur results suggest that D2 occupancy is a contributing factor for the mechanism of antipsychotic effect in SCZ for some but not all antipsychotic medications.