Safety and Tolerability of Donepezil, Rivastigmine and Galantamine for Patients with Alzheimer’s Disease: Systematic Review of the ‘Real-World’ Evidence

Abstract

Background/Aims: The purpose of this systematic review was to compare the safety and tolerability of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine for treating mild to moderate Alzheimer’s disease (AD) patients in routine clinical practice. Methods: Electronic databases (Cochrane Library, Medline, EMBASE; accessed October 2008) and manual bibliographic searches were conducted to identify head-to-head non-randomised studies examining ChEIs for the treatment of AD. Data were extracted by 2 independent reviewers. Results: Twelve head-to-head studies comparing ChEIs met the pre-specified inclusion criteria; 6 retrospective analyses and 6 prospective cohort studies. Donepezil was the most widely studied treatment and galantamine the least widely prescribed therapy. Fewer donepezil-treated subjects withdrew due to adverse events (AEs) compared with rivastigmine and galantamine-treated subjects. The incidence of gastrointestinal (GI) AEs was lower following treatment with donepezil compared with rivastigmine and galantamine. Non-GI (CNS and cardiovascular) AEs occurred at a low frequency, and had a similar incidence in subjects treated with the different ChEIs. Conclusions: Subjects with mild to moderate AD treated in routine clinical practice with donepezil were more adherent to pharmacotherapy, and had a lower risk of GI AEs compared with rivastigmine or galantamine. This finding accords with results reported in the randomised clinical trial literature.

Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study)

“…Interestingly, in our study most of the mixed dementia patients had subcortical vascular disease. These and other studies 4,7,9,27,28 reported higher rates of nausea and vomiting in GAL treated participants, compared with placebo, consistent with our results and the generally favorable safety profile observed in previous studies in AD disease 5,25,26,29 . A systematic review 3 of 15 trials evaluating the efficacy of NIM in AD, CVD and mixed dementia found benefits of the NIM therapy on short-term outcomes of global and cognitive function, when results were pooled together, despite dementia specific etiology.…”

“…GAL has been tested in several randomized clinical trials for AD 3,16,25,26 and has been also evaluated in a systematic review, which examined its efficacy and safety for patients with vascular cognitive impairment, but also included studies enrolling mixed dementia patients 4 . Two studies were deemed eligible for the systematic review (GAL-INT-26 and GAL-INT-6), the first assessing a population with probable vascular dementia 27 and the other, a mixed population of vascular dementia and AD with simultaneous CVD patients 9,28 .…”

Cholinergic interactions between donepezil and prucalopride in human colon: potential to treat severe intestinal dysmotility

“…The fact that both of these drugs are readily available in many countries for clinical use now offers the potential for improved efficacy over prucalopride alone and improved cardiovascular and bronchial safety over the use of physostigmine. Thus, when compared with neostigmine, donepezil is safer to use, especially in the elderly (Birks, 2006;Lockhart et al, 2009) who are more likely to suffer from acute colonic pseudo-obstruction (Hyatt, 1987). Further, prucalopride has been shown to have no cardiac safety liability in elderly patients treated for constipation (Camilleri et al, 2009).…”

Regulator of G-protein Signaling-21 (RGS21) Is an Inhibitor of Bitter Gustatory Signaling Found in Lingual and Airway Epithelia

“…Perception of bitterness by the gustatory system helps to identify toxic or spoiled foods that should not be ingested; however, many nonharmful compounds also are perceived as bitter, including some artificial sweeteners and many medicines (23)(24)(25)(26)(27)(28)(29)(30). Tastant receptors have also been identified outside the gustatory system, including bitter receptors in ciliated epithelial airway and enteroendocrine cells (31)(32)(33)(34), but their function in these tissues is still being determined.…”