Estimated dopamine D(2) receptor occupancy and remission in schizophrenia: analysis of the CATIE data.

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Moriguchi S, Bies RR, Remington G, Suzuki T, Mamo DC, Watanabe K, Mimura M, Pollock BG, Uchida H

Estimated dopamine D(2) receptor occupancy and remission in schizophrenia: analysis of the CATIE data.

J Clin Psychopharmacol. 2013 Oct;33(5):682-5. doi: 10.1097/JCP.0b013e3182979a0a.

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23899638 [ View in PubMed
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Abstract

In treating schizophrenia, 65% to 80% occupancy of dopamine D(2) 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 D(2) 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 D(2) receptor occupancy levels at month 6 were estimated from plasma antipsychotic concentrations using population pharmacokinetic analysis and our D(2) prediction model. Estimated mean +/- SD peak and trough D(2) 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 D(2) occupancy of <65%). In conclusion, approximately half of patients with remission did not achieve continuous blockade of estimated D(2) receptor occupancy 5% or greater. These results extend our previous findings and suggest that sustained D(2) receptor occupancy greater than 65% may not always be necessary for the maintenance treatment of schizophrenia.

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