Estimating Dopamine D-2 Receptor Occupancy for Doses of 8 Antipsychotics: A Meta-Analysis

Irene M. Lako, Edwin R. van den Heuvel, Henrikus Knegtering, Richard Bruggeman, Katja Taxis*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

52 Citations (Scopus)

Abstract

Rationale: Dose equivalents based on dopamine D-2 receptor occupancy can be used to compare antipsychotics on D-2 receptor-mediated (adverse) effects such as extrapyramidal symptoms and altered emotional experiences. Previous meta-analyses modeling the dose-occupancy relationship hardly addressed potential heterogeneity of the imaging data.

Objectives: To model the relationship between dose and D-2 receptor occupancy for a series of frequently prescribed antipsychotics while addressing the potential heterogeneity of the imaging data.

Methods: We conducted a meta-analysis on published D-2 receptor occupancy data (positron emission tomography and single-photon emission computed tomography) in patients with schizophrenia treated with antipsychotics. A nonlinear mixed effects model estimated the median D-2 receptor occupancy for a given antipsychotic dose. Heterogeneity between studies was investigated by incorporating study as a random effect in the model, in addition to patient-and study-specific explanatory variables.

Results: Included were 51 studies, describing 606 patients (mean +/- SD age, 32.2 +/- 10.8 years; 25.7% female). The models described the dose-occupancy relationship with narrow confidence bands around the therapeutic dose range. Maximum occupancy (95% confidence interval [CI]) was estimated for haloperidol (91.9%; 95% CI, 86.1-97.8), risperidone (92.4%; 95% CI, 81.8-100), olanzapine (96.5%; 95% CI, 85.8-100), clozapine (61.7%; 95% CI, 49.2-74.2), quetiapine (49.1%; 95% CI, 18.7-79.6), aripiprazole (86.9%; 95% CI, 78.2-95.7), ziprasidone (82.9%; 95% CI, 44.9-100), and amisulpride (85.0%; 95% CI, 68.5-100). Interindividual differences explained most of the variability in occupancy values, besides significant heterogeneity between studies.

Conclusions: Dose-occupancy functions estimated the median level of dopamine D-2 receptor occupancy for 8 frequently prescribed antipsychotics in patients with schizophrenia. These dose equivalents can be used to compare antipsychotic effects in epidemiological studies and clinical practice.

Original languageEnglish
Pages (from-to)675-681
Number of pages7
JournalJournal of Clinical Psychopharmacology
Volume33
Issue number5
DOIs
Publication statusPublished - Oct-2013

Keywords

  • dopamine D-2 receptor occupancy
  • antipsychotic dose
  • schizophrenia
  • positron emission tomography (PET) imaging study
  • DOUBLE-BLIND PET
  • SCHIZOPHRENIC-PATIENTS
  • SUBJECTIVE EXPERIENCE
  • ATYPICAL ANTIPSYCHOTICS
  • EMISSION-TOMOGRAPHY
  • POOLED ANALYSIS
  • PLASMA-LEVELS
  • HUMAN BRAIN
  • TIME-COURSE
  • DRUG

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