A Long-Term Comparison of Galantamine and Donepezil in the Treatment of Alzheimer’s Disease
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To compare the long-term efficacy and safety of galantamine 24 mg/day and donepezil 10 mg/day in patients with Alzheimer’s disease.
Patients and Study Design
This was a rater-blinded, randomised, parallel-group multicentre study (18 outpatient clinics) in the UK. 182 patients (69 male, 113 female) with Alzheimer’s disease were randomised to galantamine (n = 94) or donepezil (n = 88) for 52 weeks.
Main outcome measures
The effects of galantamine and donepezil on function using the Bristol Activities of Daily Living Scale (BrADL); cognition using the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog/11); behaviour using the Neuropsychiatric Inventory (NPI); caregiver burden using the Screen for Caregiver Burden; and safety were assessed.
BrADL total scores showed no significant difference between treatment groups in mean change from baseline to week 52. In the total population, in terms of cognition, galantamine patients’ scores on the MMSE at week 52 did not differ significantly from baseline (−0.52 ± 0.39, p < 0.5 vs baseline), whereas donepezil patients’ scores deteriorated significantly from baseline (−1.58 ± 0.42, p < 0.0005 vs baseline). The between-group difference in MMSE change, which showed a trend for superiority of galantamine, did not reach statistical significance (p < 0.1). In the ADAS-cog/11 analysis, between-group differences for the total population were not significant, whereas galantamine-treated patients with MMSE scores of 12–18 demonstrated an increase (worsening) in the ADAS-cog/11 score of 1.61 ± 0.80 versus baseline, compared with an increase of 4.08 ± 0.84 for patients treated with donepezil, with a significant between-group difference in favour of galantamine (p ≤ 0.05). More caregivers of patients receiving galantamine reported reductions in burden compared with donepezil. Changes from baseline in NPI were similar for both treatments.
Both treatments were well tolerated; most adverse events were transient and of mild-to-moderate intensity, and were consistent with the findings of previous clinical trials.
Significant advantages were found in the treatment response to galantamine (versus donepezil) on cognition as measured by response rates on the MMSE and ADAS-cog/11.
KeywordsMMSE Score Galantamine Caregiver Burden Neuronal Nicotinic Receptor Baseline MMSE Score
The principal investigators of this study were: I. McKeith, Newcastle-Upon-Tyne, UK; J. Haworth, Bristol, UK; D. Wilkinson, Southampton, UK; R.W. Jones, Bath, UK; A. Bayer, Penarth, UK; R.J. Smith, Bradford, UK; B. Lawlor, Dublin, Ireland; P. Crome, Stoke-on-Trent, UK; C. Bulpitt, London, UK; B. Boothman, Preston, UK; M. Evans, Chester, UK; A. Barker, Barton-on-Sea, UK; S. Simpson, Herrison, UK; A. O’Brien, Westcliff on Sea, UK; M. Doran, Fazakerley, UK; C.M. Bonthala, Northampton, UK; R. Bullock, Swindon, UK; and F.G. Inglis, Irvine, UK
Gordon Wilcock, Hilary Coles, Ian Howe and Roger Bullock assisted in trial design. Roger Bullock was an investigator in the trial. Ian Howe, Sean Lilienfeld, Luc Truyen, Hilary Coles and Young Zhu assisted in data collection. Gordon Wilcock, Ian Howes, Roger Bullock, Sean Lilienfeld, Luc Truyen and Young Zhu assisted in data analysis as well as preparation, review and final approval of the clinical trial results. All authors participated in the preparation, review and final approval of the manuscript. Young Zhu is the project statistician.
Activities related to study design, data collection and analysis, as well as preparation and review of the manuscript were funded in whole or in part by Janssen-Cilag UK, Janssen Pharmaceutica Products L.P. and Shire Pharmaceuticals Ltd. Ian Howe is an employee of Shire Pharmaceuticals Ltd; Hilary Coles is an employee of Janssen-Cilag UK; Sean Lilienfeld and Luc Truyen are employees of Janssen Pharmaceutica Products L.P.; Gordon Wilcock and Roger Bullock have received honoraria from various pharmaceutical companies for consulting and lectures.
- 10.Corey-Bloom J, Anand R, Veach J, for the ENA 713 B352 Study Group. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer. Int J Geriatr Psychopharmacol 1998; 1: 55–65Google Scholar
- 12.Reminyl® [prescribing information]. Titusville (NJ): Janssen Pharmaceutica Products, L.P., 2001Google Scholar
- 28.Jones RW, Passmore P, Wetterberg P, et al. First head to head study comparing the tolerability and efficacy of donepezil and galantamine in Alzheimer’s disease [poster]. 7th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy; 2002 Apr 3–6; Geneva, SwitzerlandGoogle Scholar
- 32.Ariceptsu™ [prescribing information]. London (UK): Eisai Ltd., 2002Google Scholar
- 35.Hills R, Gray R, Stowe R, et al. Drop-out bias undermines findings of improved functionality with cholinesterase inhibitors [poster]. International Conference on Alzheimer’s Disease and Related Disorders, 2002 Jul 20–25; Stockholm, SwedenGoogle Scholar
- 40.National Institute for Clinical Excellence. Guidance on the use of donepezil, rivastigmine and galantamine for the treatment of Alzheimer’s disease. Technology Appraisal Guidance No. 19 [online]. Available from URL: http://www.nice.org.uk/pdf/ALZHEIMER_full_guidance.pdf