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A Systematic Review of Aripiprazole—Dose, Plasma Concentration, Receptor Occupancy, and Response: Implications for Therapeutic Drug Monitoring
Objective: To evaluate relationships between aripiprazole dose, plasma level, pharmacologic activity, and clinical outcome in order to evaluate the potential for therapeutic drug monitoring.
Data Sources: In August 2008, we searched Embase, MEDLINE, and PubMed databases using the keywords aripiprazole, plasma levels, plasma concentration, and therapeutic drug monitoring.
Study Selection: Twenty-one reports were retrieved. Eight studies investigating the relationship between blood concentrations of aripiprazole and dose, dopamine D2/D3 occupancy, and/or outcome and adverse effects were then selected.
Data Extraction: All data concerning plasma or serum concentrations of aripiprazole were included if concentrations were reported in relation to a dose, dopamine occupancy, or clinical outcome. Those reports solely investigating drug interactions were not included.
Data Synthesis: A strong correlation exists between aripiprazole dose and plasma concentration. Positron emission tomography analyses suggest that there are significant relationships between dopamine receptor occupancy and both aripiprazole dose and blood concentration. Dopamine receptor occupancy appears to reach a plateau at doses above 10 mg, supporting the observation found in dose-response studies that 10 mg/d is the optimal dose for aripiprazole.
Conclusions: The dose range for aripiprazole is well defined, and it reliably predicts plasma level, dopamine receptor occupancy, and clinical response. Plasma level variation appears to have minimal impact on clinical response, but it may predict some adverse effects. A putative target plasma level range of between 150 and 210 ng/mL is suggested. Therapeutic drug monitoring has limited value in the clinical use of aripiprazole, but it may be useful in assuring adherence and optimizing response in individuals.
J Clin Psychiatry
Submitted: January 16, 2009; accepted June 9, 2009.
Online ahead of print: June 1, 2010 (doi:10.4088/JCP.09r05060gre).
Corresponding author: David Taylor, MSc, PhD, MRPharmS, Pharmacy Department, Maudsley Hospital, Denmark Hill, London SE5 8AZ, UK ().