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

Schizophr Res. 2012 Sep;140(1-3):214-20. doi: 10.1016/j.schres.2012.06.027. Epub 2012 Jul 12.


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.

Publication types

  • Meta-Analysis

MeSH terms

  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Humans
  • Positron-Emission Tomography
  • Protein Binding / drug effects
  • Psychiatric Status Rating Scales
  • Receptors, Dopamine D2 / metabolism*
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism*
  • Tomography, Emission-Computed, Single-Photon
  • Treatment Outcome


  • Antipsychotic Agents
  • Receptors, Dopamine D2