Memantine in patients with moderate to severe alzheimer's disease: Meta-analyses using realistic definitions of response

Dementia and Geriatric Cognitive Disorders

Volumn 37, Issue 1-2, 2014, Pages 71-85

  Wilkinson, David ^a   Wirth, Yvonne ^b   Goebel, Claus ^c  

^a MOORGREEN HOSPITAL   (United Kingdom)

^b Wirth Consulting   (Germany)

^c MERZ PHARMACEUTICALS GMBH   (Germany)

Author keywords

Activities of daily living; Alzheimer's disease; Clinical worsening; Cognition; Disease progression; Global status; Memantine; Meta analysis; Randomised controlled trials

Indexed keywords

MEMANTINE; PLACEBO; DONEPEZIL; GALANTAMINE; RIVASTIGMINE;

ADULT; AGED; ALZHEIMER DISEASE; ARTICLE; COGNITION; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; META ANALYSIS; MIDDLE AGED; MINI MENTAL STATE EXAMINATION; MULTICENTER STUDY; POST HOC ANALYSIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; COGNITION ASSESSMENT; DISEASE SEVERITY; FUNCTIONAL ASSESSMENT; MENTAL DETERIORATION; MULTICENTER STUDY (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTEMATIC REVIEW; TREATMENT RESPONSE;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; COGNITION; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; DISEASE PROGRESSION; DOPAMINE AGENTS; EXECUTIVE FUNCTION; FEMALE; HUMANS; MALE; MEMANTINE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; ODDS RATIO; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84896706419     PISSN: 14208008     EISSN: 14219824     Source Type: Journal    
DOI: 10.1159/000353801     Document Type: Article

References (54)

1. European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP): Guideline on medicinal products for the treatment of Alzheimer's disease and other dementias. CPMP/EWP/553/95 Rev 1, July 24, 2008. http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2009/ 09/WC500003562.pdf (accessed February 12, 2013).
2. McShane R, Areosa Sastre A, Minakaran N: Memantine for dementia. Cochrane Database Syst Rev 2006; CD003154.
3. Winblad B, Jones RW, Wirth Y, Stöffler A, Möbius HJ: Memantine in moderate to severe Alzheimer's disease: a meta-analysis of randomised clinical trials. Dement Geriatr Cogn Disord 2007; 24: 20-27.
4. Doody RS, Tariot PN, Pfeiffer E, Olin JT, Graham SM: Meta-analysis of six-month memantine trials in Alzheimer's disease. Alzheimers Dement 2007; 3: 7-17.
5. Winblad B, Brodaty H, Gauthier S, Morris JC, Orgogozo JM, Rockwood K, Schneider L, Takeda M, Tariot P, Wilkinson D: Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment success? Int J Geriatr Psychiatry 2001; 16: 653-666.
6. Geldmacher DS, Frolich L, Doody RS, Erkinjuntti T, Vellas B, Jones RW, Banerjee S, Lin P, Sano M: Realistic expectations for treatment success in Alzheimer's disease. J Nutr Health Aging 2006; 10: 417-429.
7. Wilkinson D, Andersen HF: Analysis of the effect of memantine in reducing the worsening of clinical symptoms in patients with moderate to severe Alzheimer's disease. Dement Geriatr Cogn Disord 2007; 24: 138-145.
8. European Medicines Agency (EMA): Ebixa, Memantine hydrochloride. Summary of product characteristics. http://www.ema.europa.eu/docs/en-GB/document- library/EPAR-Product-Information/human/000463/WC500058763.pdf (accessed February 12, 2013).
9. Hellweg R, Wirth Y, Janetzky W, Hartmann S: Efficacy of memantine in delaying clinical worsening in Alzheimer's disease (AD): responder analyses of nine clinical trials with patients with moderate to severe AD. Int J Geriatr Psychiatry 2012; 27: 651-656.
10. Institute for Quality and Efficiency in Health Care (IQWiG): Memantin bei Alzheimer Demenz: Ergebnisse der unpublizierten Studien IE2101 und MEM-MD-22 sowie unpublizierter Responderanalysen (Arbeitspapier) [Memantine in Alzheimer's disease: results of the unpublished studies IE2101 and MEM-MD-22 as well as unpublished responder analyses (working paper)]. Version 1.0, July 1, 2010. https://www.iqwig.de/download/Arbeitspapier-zu-Memantin-bei-Alzheimer-Demenz. pdf (accessed February 12, 2013).
11. Peskind ER, Potkin SG, Pomara N, Ott BR, Graham SM, Olin JT, McDonald S, Memantine MEM-MD-10 Study Group: Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Am J Geriatr Psychiatry 2006; 14: 704-715.
12. Bakchine S, Loft H: Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. J Alzheimers Dis 2008; 13: 97-107, corrected and republished from J Alzheimers Dis 2007; 11: 471-479.
13. Porsteinsson AP, Grossberg GT, Mintzer J, Olin JT, Memantine MEM-MD-12 Study Group: Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Curr Alzheimer Res 2008; 5: 83-89.
14. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, Memantine Study Group: Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003; 348: 1333-1341.
15. van Dyck CH, Tariot PN, Meyers B, Malca Resnick E, Memantine MEM-MD-01 Study Group: A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis Assoc Disord 2007; 21: 136-143.
16. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, Memantine Study Group: Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004; 291: 317-324.
17. Homma A, Kitamura S, Yoshimura I: Efficacy of memantine in patients with moderately severe to severe Alzheimer's disease in Japan (dose-finding study). Poster presented at the 11th Congress of the European Federation of Neurological Societies (EFNS), Brussels, Belgium, August 25-28, 2007.
18. Chen X, Zhang Z, Wang X, Shu L, Qian C, Yao J, Chen S, Xiao S, Tang H: A double-blind, randomised, placebocontrolled study of the efficacy and tolerability of memantine in Chinese patients with dementia of the Alzheimer's type. Chin J Neurol 2007; 40: 364-368.
19. Forest Laboratories, Inc: Summary clinical study report-study MEM-MD-22. 2006. http://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?-file-id= scsr/SCSR-MEM-MD-22-final.pdf (accessed February 12, 2013).
20. Saxton J, Swihart AA: Neuropsychological assessment of the severely impaired elderly patient. Clin Geriatr Med 1989; 5: 531-543.
21. Rosen WG, Mohs RC, Davis KL: A new rating scale for Alzheimer's disease. Am J Psychiatry 1984; 141: 1356-1364.
22. van der Kam P, Mol F, Wimmers MFHC: Beoordelingsschaal voor oudere patienten (BOP). The Netherlands, Van Loghum Slaterus, 1971.
23. Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S: An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11(suppl 2):S33-S39.
24. Galasko D, Schmitt F, Thomas R, Jin S, Bennett D, Alzheimer's Disease Cooperative Study: Detailed assessment of activities of daily living in moderate to severe Alzheimer's disease. J Int Neuropsychol Soc 2005; 11: 446-453.
25. Knopman DS, Knapp MJ, Gracon SI, Davis CS: The Clinician Interview-Based Impression (CIBI): a clinician's global change rating scale in Alzheimer's disease. Neurology 1994; 44: 2315-2321.
26. Reisberg B, Ferris SH: Clinician's interview-based impression of change-plus; in Kelly C, Newton-Howes G (eds): Guide to Assessment Scales in Dementia. London, Science Press, 1994.
27. Schneider LS, Olin JT, Doody RS, Clark CM, Morris JC, Reisberg B, Schmitt FA, Grundman M, Thomas RG, Ferris SH: Validity and reliability of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11(suppl 2):S22-S32.
28. Institute for Quality and Efficiency in Health Care (IQWiG): Allgemeine Methoden [General Methods]. Version 3.0, May 27, 2008. https://www.iqwig.de/ download/IQWiG-Methoden-Version-3-0.pdf, English translation: https://www.iqwig.de/download/IQWiG-General-methods-V-3-0.pdf (accessed February 12, 2013).
29. Raskind M, Kumar V, Malaty L, Messina J, Hartman R, Anand R: Rivastigmine for Alzheimer's disease: improvement versus reduced worsening. Prim Care Companion J Clin Psychiatry 2000; 2: 134-138.
30. Mohs RC: The Alzheimer's Disease Assessment Scale. Int Psychogeriatr 1996; 8: 195-203.
31. Stern RG, Mohs RC, Davidson M, Schmeidler J, Silverman J, Kramer-Ginsberg E, Searcey T, Bierer L, Davis KL: A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration. Am J Psychiatry 1994; 151: 390-396.
32. Rockwood K, Fay S, Gorman M: The ADAS-Cog and clinically meaningful change in the VISTA clinical trial of galantamine for Alzheimer's disease. Int J Geriatr Psychiatry 2010; 25: 191-201.
33. Institute for Quality and Efficiency in Health Care (IQWiG): Final Report-Commission No. A05-19C: Memantin bei Alzheimer Demenz [Memantine in Alzheimer's disease]. Version 1.0, July 8, 2009. https://www.iqwig.de/download/ A05-19C-Vorbericht-Memantin-bei-Alzheimer-Demenz.pdf (accessed February 12, 2013).
34. Revicki D, Hays RD, Cella D, Sloan J: Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol 2008; 61: 102-109.
35. Norman GR, Sloan JA, Wyrwich KW: Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 2003; 41: 582-592.
36. Howard R, Phillips P, Johnson T, O'Brien J, Sheehan B, Lindesay J, Bentham P, Burns A, Ballard C, Holmes C, McKeith I, Barber R, Dening T, Ritchie C, Jones R, Baldwin A, Passmore P, Findlay D, Hughes A, Macharouthu A, Banerjee S, Jones R, Knapp M, Brown RG, Jacoby R, Adams J, Griffin M, Gray R: Determining the minimum clinically important differences for outcomes in the DOMINO trial. Int J Geriatr Psychiatry 2011; 26: 812-817.
37. Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, Burns A, Dening T, Findlay D, Holmes C, Hughes A, Jacoby R, Jones R, Jones R, McKeith I, Macharouthu A, O'Brien J, Passmore P, Sheehan B, Juszczak E, Katona C, Hills R, Knapp M, Ballard C, Brown R, Banerjee S, Onions C, Griffin M, Adams J, Gray R, Johnson T, Bentham P, Phillips P: Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med 2012; 366: 893-903.
38. Sloan J, Symonds T, Vargas-Chanes D, Fridley B: Practical guidelines for assessing the clinical significance of health-related quality of life changes within clinical trials. Drug Inf J 2003; 37: 23-31.
39. Sloan JA: Assessing the minimally clinically significant difference: scientific considerations, challenges and solutions. COPD 2005; 2: 57-62.
40. van Dyck CH, Schmitt FA, Olin JT, Memantine MEM-MD-02 Study Group: A responder analysis of memantine treatment in patients with Alzheimer disease maintained on donepezil. Am J Geriatr Psychiatry 2006; 14: 428-437.
41. Lopez OL, Becker JT, Saxton J, Sweet RA, Klunk W, DeKosky ST: Alteration of a clinically meaningful outcome in the natural history of Alzheimer's disease by cholinesterase inhibition. J Am Geriatr Soc 2005; 53: 83-87.
42. Emre M, Mecocci P, Stender K: Pooled analyses on cognitive effects of memantine in patients with moderate to severe Alzheimer's disease. J Alzheimers Dis 2008; 14: 193-199.
43. Ferris S, Ihl R, Robert P, Winblad B, Gatz G, Tennigkeit F, Gauthier S: Treatment effects of memantine on language in moderate to severe Alzheimer's disease patients. Alzheimers Dement 2009; 5: 369-374.
44. Gauthier S, Loft H, Cummings J: Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis. Int J Geriatr Psychiatry 2008; 23: 537-545.
45. Atri A, Molinuevo JL, Lemming O, Wirth Y, Pulte I, Wilkinson D: Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy. Alzheimers Res Ther 2013; 5: 6.
46. Wilkinson D, Schindler R, Schwam E, Waldemar G, Jones RW, Gauthier S, Lopez OL, Cummings J, Xu Y, Feldman HH: Effectiveness of donepezil in reducing clinical worsening in patients with mild-to-moderate Alzheimer's disease. Dement Geriatr Cogn Disord 2009; 28: 244-251.
47. Berghmans R: Is delay of clinical worsening a valuable goal in the treatment of Alzheimer's disease? Int J Geriatr Psychiatry 2012; 27: 657, author reply 658.
48. Farlow MR, Graham SM, Alva G: Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trials. Drug Saf 2008; 31: 577-585.
49. US Department of Health and Human Services Food and Drug Administration (FDA): Guidance for industry. Patient-reported outcome measures: use in medical product development to support labeling claims. December 2009. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM193282.pdf (accessed February 12, 2013).
50. Institute for Quality and Efficiency in Health Care (IQWiG): Rapid Report-Commission No. A10-06: Responderanalysen zu Memantin bei Alzheimer Demenz [Responder analyses on memantine in Alzheimer's disease]. Version 1.0, March 28, 2011. https://www.iqwig.de/download/A10-06-Rapid-Report-Responderanalysen- zu-Memantin-bei-Alzheimer-Demenz.pdf (accessed February 12, 2013).
51. Wilkinson D: A review of the effects of memantine on clinical progression in Alzheimer's disease. Int J Geriatr Psychiatry 2012; 27: 769-776.
52. Atri A, Rountree SD, Lopez OL, Doody RS: Validity, significance, strengths, limitations, and evidentiary value of real-world clinical data for combination therapy in Alzheimer's disease: comparison of efficacy and effectiveness studies. Neurodegener Dis 2012; 10: 170-174.
53. Atri A, Shaughnessy LW, Locascio JJ, Growdon JH: Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 2008; 22: 209-221.
54. Lopez OL, Becker JT, Wahed AS, Saxton J, Sweet RA, Wolk DA, Klunk W, DeKosky ST: Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry 2009; 80: 600-607.