Therapeutic drug monitoring for dose optimization in Alzheimer's disease and in dementia with Lewy bodies: A randomized single-blinded clinical trial.

Background: Previous evidence suggests serum concentrations of donepezil varies in clinical populations and that a dose higher than standard may have additional positive effect on cognition. Therapeutic drug monitoring (TDM) is a tool for dose optimization (DO) whereby treatment is adjusted based on previous quantification of the prescribed drug.

Objective: Investigate whether TDM-based DO of donepezil or memantine improves clinical outcomes and/or reduce the frequency of adverse reactions (ARs) in neurodegenerative conditions commonly treated with these two study drugs.

Methods: Single-blinded 1:1 randomized controlled study in an outpatient memory clinic. Eligible participants either newly diagnosed with Alzheimer's disease dementia (AD), dementia with Lewy bodies (DLB), or Parkinson's disease dementia (PDD) scheduled for treatment with donepezil or memantine. The intervention group received TDM based DO. The control group received DO solely based on clinical assessment. Clinical outcomes were change in Mini-Mental State Examination, Addenbrooke's Cognitive Examination, Neuropsychiatric Inventory, and Disability Assessment in Dementia from baseline to 12 months. Additionally, data on incidence and severity of ARs and proportion of participants with a serum concentration within the therapeutic reference range were collected.

Results: 132 participants recruited (125 AD, 7 DLB, none with PDD) of whom 107 completed the study (101 AD and 6 DLB), fewer in the control group than planned. Statistical analysis did not reveal significant differences between groups neither for clinical outcomes nor for frequency of ARs.

Conclusions: TDM based DO did not significantly improve clinical outcomes nor reduce the frequency of ARs albeit important caveats to the results apply.

Clincialtrialsgov identifier: NCT04117178 (first posted October 7, 2019).