Type your tag names separated by a space and hit enter

Donepezil and memantine for moderate-to-severe Alzheimer's disease.

Abstract

BACKGROUND

Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.

METHODS

We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.

RESULTS

Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone.

CONCLUSIONS

In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.).

Links

  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom. robert.j.howard@kcl.ac.uk

    , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

    Source

    The New England journal of medicine 366:10 2012 Mar 08 pg 893-903

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Cholinesterase Inhibitors
    Donepezil
    Double-Blind Method
    Drug Synergism
    Drug Therapy, Combination
    Excitatory Amino Acid Antagonists
    Female
    Humans
    Indans
    Kaplan-Meier Estimate
    Male
    Memantine
    Patient Dropouts
    Piperidines
    Psychological Tests
    Receptors, N-Methyl-D-Aspartate
    Treatment Outcome

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22397651

    Citation

    Howard, Robert, et al. "Donepezil and Memantine for Moderate-to-severe Alzheimer's Disease." The New England Journal of Medicine, vol. 366, no. 10, 2012, pp. 893-903.
    Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med. 2012;366(10):893-903.
    Howard, R., McShane, R., Lindesay, J., Ritchie, C., Baldwin, A., Barber, R., ... Phillips, P. (2012). Donepezil and memantine for moderate-to-severe Alzheimer's disease. The New England Journal of Medicine, 366(10), pp. 893-903. doi:10.1056/NEJMoa1106668.
    Howard R, et al. Donepezil and Memantine for Moderate-to-severe Alzheimer's Disease. N Engl J Med. 2012 Mar 8;366(10):893-903. PubMed PMID: 22397651.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Donepezil and memantine for moderate-to-severe Alzheimer's disease. AU - Howard,Robert, AU - McShane,Rupert, AU - Lindesay,James, AU - Ritchie,Craig, AU - Baldwin,Ashley, AU - Barber,Robert, AU - Burns,Alistair, AU - Dening,Tom, AU - Findlay,David, AU - Holmes,Clive, AU - Hughes,Alan, AU - Jacoby,Robin, AU - Jones,Rob, AU - Jones,Roy, AU - McKeith,Ian, AU - Macharouthu,Ajay, AU - O'Brien,John, AU - Passmore,Peter, AU - Sheehan,Bart, AU - Juszczak,Edmund, AU - Katona,Cornelius, AU - Hills,Robert, AU - Knapp,Martin, AU - Ballard,Clive, AU - Brown,Richard, AU - Banerjee,Sube, AU - Onions,Caroline, AU - Griffin,Mary, AU - Adams,Jessica, AU - Gray,Richard, AU - Johnson,Tony, AU - Bentham,Peter, AU - Phillips,Patrick, PY - 2012/3/9/entrez PY - 2012/3/9/pubmed PY - 2012/3/17/medline SP - 893 EP - 903 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 366 IS - 10 N2 - BACKGROUND: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. METHODS: We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS. RESULTS: Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone. CONCLUSIONS: In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/22397651/Donepezil_and_memantine_for_moderate_to_severe_Alzheimer's_disease_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa1106668?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=www.ncbi.nlm.nih.gov DB - PRIME DP - Unbound Medicine ER -