Antipsychotics, dopamine D₂ receptor occupancy and clinical improvement in schizophrenia: a meta-analysis.
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.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Zeynep
Z
Yilmaz
Clement C
CC
Zai
Rudi
R
Hwang
Steve
S
Mann
Tamara
T
Arenovich
Gary
G
Remington
Zafiris J
ZJ
Daskalakis
D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2