Relationship Between Daily Dose, Plasma Concentrations, Dopamine Receptor Occupancy, and Clinical Response to Quetiapine: A Review

Objective: To assess the relationships among quetiapine blood concentration, daily dose, dopamine receptor occupancy, and clinical outcome in order, if possible, to define a target plasma level range in which therapeutic response is enhanced and adverse events are minimized.

Data Sources: A search of the database Embase from 1974 to March 2009 and the databases MEDLINE and PubMed from 1966 to March 2009 was conducted. The drug name quetiapine was searched with each of the terms plasma levels, plasma concentration, therapeutic drug monitoring, and dopamine occupancy.

Study Selection: The search uncovered 42 relevant articles. All published reports of quetiapine plasma or serum concentration were considered for inclusion if reported in relation to a dose, clinical outcome, or dopamine occupancy. After application of exclusion criteria, 20 articles remained.

Data Extraction: Trials designed primarily to investigate an interaction between quetiapine and another medication were excluded, as were those designed to compare methods of blood sample analysis.

Data Synthesis: There was a weak correlation between quetiapine dose and measured plasma concentration (from trough samples). Quetiapine dose was correlated with central dopamine D2 occupancy, although the relationship between plasma level and D2 occupancy is less clear.

Conclusions: The dose-response relationship for (immediate-release) quetiapine is established. Data on plasma concentration-response relationships are not sufficiently robust to allow determination of a therapeutic plasma level range for quetiapine. Therapeutic drug monitoring procedures are thus probably not routinely useful in optimizing quetiapine dose. Further examination of the relationship between peak quetiapine plasma concentration and clinical response is necessary.

J Clin Psychiatry 2011;72(8):1108-1123

Submitted: October 5, 2009; accepted February 16, 2010.

Online ahead of print: January 25, 2011 (doi:10.4088/JCP.09r05739yel).

Corresponding author: David Taylor, Phd, Pharmacy Department, Maudsley Hospital, Denmark Hill, London SE5 8AZ, UK ([email protected]).