Cortical Dopamine D2/D3 Receptors Are a Common Site of Action for Antipsychotic Drugs—An Original Patient Data Meta-analysis of the SPECT and PET In Vivo Receptor Imaging Literature

摘要

Subject numbers in neuroreceptor imaging studies of antipsychotic treatment in schizophrenia are generally insufficient to directly test the relationship of regional D2/D3 and 5HT2A receptor binding to clinical efficacy. We selected positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies of antipsychotic dose vs occupancy at both temporal cortex and striatal D2/D3 receptors. We selected corresponding SPECT and PET studies of 5HT2A receptor occupancy. We also selected randomized double-blind clinical trials of antipsychotics, where patients were treated with randomly assigned fixed doses. For each antipsychotic drug, we compared the optimum effective antipsychotic dose with the dose inducing maximal occupancy of D2/D3 receptors in striatum and in temporal cortex as well as at 5HT2A receptors. Both first- and second-generation antipsychotic (FGA, SGA) drugs produced high temporal cortex D2/D3 occupancy. Only FGA produced high striatal D2/D3 receptor occupancy. The clinically effective dose showed correlation with doses inducing maximal dopamine D2/D3 receptor occupancy both in striatum and in temporal cortex, the strongest correlation being with temporal cortex binding. Extrapyramidal side effects (EPSE) were primarily related to striatal D2/D3 receptor occupancy. There was no correlation between 5HT2A occupancy and clinically effective dose. We conclude that cortical dopamine D2/D3 receptor occupancy is involved in antipsychotic efficacy, with striatal D2/D3 occupancy having a likely therapeutic role while also inducing EPSE. We found no evidence for 5HT2A blockade involvement in antipsychotic action, although we cannot exclude this possibility.