Abstract
In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean ± SD age, 48.8 ± 13.8. years; male [N = 14]; Asians [N = 23], Caucasians [N = 12]; risperidone [N = 20] at 3.2 ± 2.3. mg/day, and olanzapine [N = 15] at 9.2 ± 4.9. mg/day) between September and December 2010. 48.6% (N = 17) did not achieve a continuous blockade of ≥ 65%. Moreover, 11.4% (N = 4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥ 65%. The results suggest that sustained D2 receptor occupancy levels of ≥ 65% may not always be necessary for the maintenance treatment of schizophrenia.
| Original language | English |
|---|---|
| Pages (from-to) | 182-187 |
| Number of pages | 6 |
| Journal | Progress in Neuro-Psychopharmacology and Biological Psychiatry |
| Volume | 37 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2012 Apr 27 |
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Keywords
- Antipsychotic
- Dopamine
- Maintenance
- Olanzapine
- Risperidone
- Schizophrenia
ASJC Scopus subject areas
- Biological Psychiatry
- Pharmacology
Cite this
Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia : A cross-sectional study. / Mizuno, Yuya; Bies, Robert R.; Remington, Gary; Mamo, David C.; Suzuki, Takefumi; Pollock, Bruce G.; Tsuboi, Takashi; Watanabe, Koichiro; Mimura, Masaru; Uchida, Hiroyuki.
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 37, No. 1, 27.04.2012, p. 182-187.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia
T2 - A cross-sectional study
AU - Mizuno, Yuya
AU - Bies, Robert R.
AU - Remington, Gary
AU - Mamo, David C.
AU - Suzuki, Takefumi
AU - Pollock, Bruce G.
AU - Tsuboi, Takashi
AU - Watanabe, Koichiro
AU - Mimura, Masaru
AU - Uchida, Hiroyuki
PY - 2012/4/27
Y1 - 2012/4/27
N2 - In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean ± SD age, 48.8 ± 13.8. years; male [N = 14]; Asians [N = 23], Caucasians [N = 12]; risperidone [N = 20] at 3.2 ± 2.3. mg/day, and olanzapine [N = 15] at 9.2 ± 4.9. mg/day) between September and December 2010. 48.6% (N = 17) did not achieve a continuous blockade of ≥ 65%. Moreover, 11.4% (N = 4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥ 65%. The results suggest that sustained D2 receptor occupancy levels of ≥ 65% may not always be necessary for the maintenance treatment of schizophrenia.
AB - In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean ± SD age, 48.8 ± 13.8. years; male [N = 14]; Asians [N = 23], Caucasians [N = 12]; risperidone [N = 20] at 3.2 ± 2.3. mg/day, and olanzapine [N = 15] at 9.2 ± 4.9. mg/day) between September and December 2010. 48.6% (N = 17) did not achieve a continuous blockade of ≥ 65%. Moreover, 11.4% (N = 4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥ 65%. The results suggest that sustained D2 receptor occupancy levels of ≥ 65% may not always be necessary for the maintenance treatment of schizophrenia.
KW - Antipsychotic
KW - Dopamine
KW - Maintenance
KW - Olanzapine
KW - Risperidone
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84862787687&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862787687&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2011.12.013
DO - 10.1016/j.pnpbp.2011.12.013
M3 - Article
VL - 37
SP - 182
EP - 187
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
IS - 1
ER -