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

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

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Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.



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.


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).


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.


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.

[Indexed for MEDLINE]

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