Therapeutic Drug Monitoring (TDM) of donepezil in patients with Alzheimers dementia

Background: For donepezil, a therapeutic reference range of 30 – 75 ng/ml is recommended for TDM. The aim of this study was to analyze if higher doses than the approved 5 and 10 mg are necessary to reach this suggested concentrations and if serum-levels up to 50 ng/ml are really necessary to have a maximum clinical effect, investigated by previous studies. Methods: Data were analyzed retrospectively from patients with Alzheimers dementia (AD) who had been treated with donepezil under naturalistic conditions and for whom blood level measurements had been requested. Results: The analysis included 87 patients (mean ± SD age 71.6 ± 8.6 years, 39.8% female) with 171 serum-levels. Overall, 62 serum-levels (36.3%) were below, 102 (59.6%) within and 7 (4.1%) above the recommended therapeutic reference range. Mean serum-concentrations were 23 ± 9 ng/ml for a dose of 5 mg/day, and 46 ± 19 ng/ml for 10 mg/day. Serum-levels correlated significantly with clinical effect. Pearson correlations-coefficient was r = 0.445 (p < 0.01, 95% CI). Patients who improved “very much” according to the clinical global impression scale had mean donepezil concentrations of 66.1 ± 19.8 ng/ml. Conclusions: Since clinical improvement correlated well with serum-levels of donepezil, TDM is recommended to maximize the efficiency of psychopharmacotherapy in AD. To reach a maximum clinical effect, the serum level of donepezil should be 50 ng/ml or higher.