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Title: Estimated dopamine D2 receptor occupancy and remission in schizophrenia : analysis of the CATIE data
Authors: Moriguchi, Sho
Bies, Robert R.
Remington, Gary
Suzuki, Takefumi
Mamo, David
Watanabe, Koichiro
Mimura, Masaru
Pollock, Bruce G.
Uchida, Hiroyuki
Keywords: Antipsychotic drugs
Receptors, Dopamine
Issue Date: 2013
Publisher: Lippincott Williams & Wilkins
Citation: Moriguchi, S., Bies, R. R., Remington, G., Suzuki, T., Mamo, D. C., Watanabe, K., ... & Uchida, H. (2013). Estimated dopamine D2 receptor occupancy and remission in schizophrenia: analysis of the CATIE data. Journal of Clinical Psychopharmacology, 33(5), 682-685.
Abstract: In treating schizophrenia, 65% to 80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms and cognitive impairments. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain clinical response. The data set from phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial was reappraised. Thirty patients receiving risperidone (12 patients), olanzapine (12 patients), or ziprasidone (6 patients) fulfilled the following definition of remission and were included: a score of 3 or less on the 8 specific items in the Positive and Negative Syndrome Scale (ie, P1, P2, P3, N1, N4, N6, G5, and G9; adopted from Andreasen et al, 2005) at the initial assessment and months 1, 2, and 6. Peak and trough D2 receptor occupancy levels at month 6 were estimated from plasma antipsychotic concentrations using population pharmacokinetic analysis and our D2 prediction model. Estimated mean ± SD peak and trough D2 receptor occupancy levels at month 6 were 70.3% ± 9.8% and 60.5% ± 20.2%, respectively; among these individuals, 46.7% (14 patients) did not achieve continuous blockade of 65% or greater (ie, trough D2 occupancy of <65%). In conclusion, approximately half of patients with remission did not achieve continuous blockade of estimated D2 receptor occupancy 5% or greater. These results extend our previous findings and suggest that sustained D2 receptor occupancy greater than 65% may not always be necessary for the maintenance treatment of schizophrenia.
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