TY - JOUR
T1 - Tardive dyskinesia in relation to estimated dopamine D2 receptor occupancy in patients with schizophrenia
T2 - Analysis of the CATIE data
AU - Yoshida, Kazunari
AU - Bies, Robert R.
AU - Suzuki, Takefumi
AU - Remington, Gary
AU - Pollock, Bruce G.
AU - Mizuno, Yuya
AU - Mimura, Masaru
AU - Uchida, Hiroyuki
N1 - Funding Information:
Data used in the preparation of this article were obtained from the limited access datasets distributed from the NIH-supported “Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia” (CATIE-Sz). This is a multisite, clinical trial of persons with schizophrenia, comparing the effectiveness of randomly assigned medication treatment. The study was supported by NIMH Contract # N01MH90001 to the University of North Carolina at Chapel Hill. The ClinicalTrials.gov identifier is NCT00014001 . The version of the dataset used was 1.0. This study was also supported by grant R01MH064173 from the National Institute of Mental Health and was ancillary to the Clinical Antipsychotic Trials of Intervention Effectiveness, N01MH90001, from the National Institute of Mental Health. This manuscript reflects the views of the authors and may not reflect the opinions or views of the CATIE-Sz Study Investigators or the NIH. No funding was provided for the present analysis.
PY - 2014/3
Y1 - 2014/3
N2 - Objective: The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE). Methods: The dataset from 218 subjects (risperidone, N = 78; olanzapine, N = 100; ziprasidone, N = 40) who presented with a score of zero on the Abnormal Involuntary Movement Scale (AIMS) at baseline in Phase 1 of the CATIE study, and remained for ≥. 6. months, was used. Peak and trough dopamine D2 receptor occupancy levels on the day of the AIMS assessment at the endpoint were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our D2 prediction model. The estimated dopamine D2 receptor occupancy levels were compared between patients who presented an AIMS score of ≥. 2 at endpoint and those with a score of zero, using the Mann-Whitney U test. Results: Estimated dopamine D2 receptor occupancy levels at trough were significantly higher in subjects who developed involuntary movements (N = 23) than those who did not (N = 195) (71.7. ±. 14.4% vs. 64.3. ±. 19.3%, p. < 0.05) while no significant difference was found in the estimated peak D2 receptor occupancy between them (75.4. ±. 8.7% vs. 72.1. ±. 9.9%, p. = 0.07). When the analyses were separately conducted for the three drugs, there were no significant differences in estimated peak or trough D2 occupancy although the values were consistently numerically higher among those developing involuntary movements. Conclusion: Greater dopamine D2 receptor blockade with antipsychotics at trough might increase the risk of tardive involuntary movements although this finding needs to be replicated in larger trials.
AB - Objective: The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE). Methods: The dataset from 218 subjects (risperidone, N = 78; olanzapine, N = 100; ziprasidone, N = 40) who presented with a score of zero on the Abnormal Involuntary Movement Scale (AIMS) at baseline in Phase 1 of the CATIE study, and remained for ≥. 6. months, was used. Peak and trough dopamine D2 receptor occupancy levels on the day of the AIMS assessment at the endpoint were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our D2 prediction model. The estimated dopamine D2 receptor occupancy levels were compared between patients who presented an AIMS score of ≥. 2 at endpoint and those with a score of zero, using the Mann-Whitney U test. Results: Estimated dopamine D2 receptor occupancy levels at trough were significantly higher in subjects who developed involuntary movements (N = 23) than those who did not (N = 195) (71.7. ±. 14.4% vs. 64.3. ±. 19.3%, p. < 0.05) while no significant difference was found in the estimated peak D2 receptor occupancy between them (75.4. ±. 8.7% vs. 72.1. ±. 9.9%, p. = 0.07). When the analyses were separately conducted for the three drugs, there were no significant differences in estimated peak or trough D2 occupancy although the values were consistently numerically higher among those developing involuntary movements. Conclusion: Greater dopamine D2 receptor blockade with antipsychotics at trough might increase the risk of tardive involuntary movements although this finding needs to be replicated in larger trials.
KW - Abnormal involuntary movement
KW - Antipsychotics
KW - CATIE
KW - Dopamine D2 receptor
KW - Schizophrenia
KW - Tardive dyskinesia
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U2 - 10.1016/j.schres.2014.01.017
DO - 10.1016/j.schres.2014.01.017
M3 - Article
C2 - 24491908
AN - SCOPUS:84895785682
SN - 0920-9964
VL - 153
SP - 184
EP - 188
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -
