Effects of switching from an AChE inhibitor to a dual AChE-BuChE inhibitor in patients with Alzheimer's disease

Abstract

Objective: Cholinesterase (ChE) inhibitors are the only medications approved for the treatment of Alzheimer's disease (AD). The features of ChE inhibitors differ considerably. In addition to acetylcholinesterase (AChE) inhibition, rivastigmine also inhibits butrylcholinesterase (BuChE), providing dual AChE and BuChE inhibition. An observational study was performed to determine the response in routine clinical practice to switching AD patients to rivastigmine from a selective AChE inhibitor when that treatment no longer delivered a satisfactory clinical response.

Research design and methods: A prospective, multicentre, 3-month observational trial in patients with mild to moderately severe AD (adjusted Mini Mental State Examination [MMSE] score 10-26) deteriorating (at least 2 adjusted MMSE points in last 6 months) on selective AChE inhibitor treatment. Adjusted MMSE, activities of daily living (ADL) and instrumental activities of daily living (IADL), the Zarit caregiver burden and global function (short Clinical Global Impression of Change, CGIC) scores were noted before the switch and 3 months after the switch.

Results: 225 patients entered the study. The switches made were from donepezil to rivastigmine in (D-R) in 188 patients, galantamine to rivastigmine (G-R) in 33 patients and donepezil to galantamine (D-G) in four patients. Ten patients discontinued due to adverse events and eight for other reasons. More than half of the switches were within 36 hours of a patient's first treatment visit. In the D-R and G-R groups, 67.7% and 66.7% of patients responded (CGIC score < or = 4), respectively. In non-responders, worsening (CGIC score 5-7) was mild in approximately 80% or more of patients. Adjusted MMSE improved after the switch from both donepezil and galantamine to rivastigmine (+0.69 +/- 3.2, p = 0.008 and +0.6 +/- 1.6, p = 0.05, respectively). Mean ADL, IADL, and Zarit scores remained stable. The proportion of patients on concomitant antipsychotic therapy diminished by 30.5% and benzodiazepines were discontinued in all patients, except one.

Conclusions: AD patients deteriorating on selective AChE inhibitor treatment can benefit from switching to a dual AChE-BuChE inhibitor, such as rivastigmine, in terms of stabilization of disease, improvement in cognitive function and reduction in the burden of concomitant psychoactive treatment. The switch was well tolerated. Confirmation of these results is required in a controlled study.