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Link to original content: https://dx.doi.org/10.2165/00003495-200666110-00015
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Memantine

A Review of its Use in Alzheimer’s Disease

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Summary

Abstract

Memantine (Ebixa®, Axura®, Namenda®, Akatinol®) is a moderate-affinity, uncompetitive, voltage-dependent, NMDA-receptor antagonist with fast on/off kinetics that inhibits excessive calcium influx induced by chronic overstimulation of the NMDA receptor. Memantine is approved in the US and the EU for the treatment of patients with moderate to severe dementia of the Alzheimer’s type.

In well designed clinical trials, oral memantine, as monotherapy or in addition to a stable dose of acetylcholinesterase inhibitors, was well tolerated during the treatment of mild to severe Alzheimer’s disease for up to 52 weeks. Memantine generally modified the progressive symptomatic decline in global status, cognition, function and behaviour exhibited by patients with moderate to severe Alzheimer’s disease in four 12- to 28-week trials. In patients with mild to moderate Alzheimer’s disease, data from three 24-week trials are equivocal, although meta-analyses indicate beneficial effects on global status and cognition. Memantine is an effective pharmacotherapeutic agent, and currently the only approved option, for the treatment of moderate to severe Alzheimer’s disease.

Pharmacological Properties

Memantine is an uncompetitive antagonist that blocks the NMDA channel with higher affinity, but less voltage-dependency, than magnesium. It moderately inhibits excitatory activity while preserving learning behaviours in vivo when compared with more potent NMDA receptor channel blockers. During pathological activation of the NMDA receptor, memantine blocks excessive calcium entry through the channel and is neuroprotective in in vitro and in vivo models.

Oral memantine is completely absorbed with an absolute bioavailability of ≈100%. Steady-state plasma concentrations, achieved after about 2 weeks of memantine 20 mg/day, range from 70 to 150 gmg/L, while the steady-state area under the plasma concentration-time curve from time 0 to 24 hours is ≈1800 gmg · h/L after 4 weeks of treatment.

Memantine is excreted in urine mostly as unchanged parent drug with the remainder being metabolised by glucuronidation, hydroxylation and N-oxidation to form NMDA-inactive metabolites. Memantine and its metabolites are primarily eliminated by the kidneys with a terminal elimination half-life of 60–100 hours. Total renal clearance in healthy volunteers is 170 mL/min/1.73m2.

Therapeutic Efficacy

The efficasy of memantine 20 mg/day has been examined in seven randomised, double-blind, placebo-controlled, multicentre trials of 12–28 weeks’ duration in patients with mild to severe Alzheimer’s disease.

In two of four trials in patients with moderate to severe Alzheimer’s disease, intent-to-treat analyses indicated that global status was significantly better with memantine than with placebo, either as monotherapy or in addition to a stable dose of donepezil. In a third trial, while global status did not differ significantly based on intent-to-treat analysis, observed-case analysis favoured memantine over placebo. However, preliminary data from a fourth trial indicate numerical differences between memantine and placebo treatment groups that were not significant.

In patients with moderate to severe Alzheimer’s disease, memantine or donepezil plus memantine also maintained superior cognitive performance and function with respect to placebo or placebo plus donepezil in two of the three trials in which they were assessed, and superior behaviour in two of the four trials.

In one published trial in patients with mild to moderate Alzheimer’s disease, memantine monotherapy significantly attenuated the decline in global status and cognition observed in placebo recipients; however, in preliminary data from another monotherapy trial, significantly greater effects with memantine seen at 12 and 18 weeks were lost at trial end, apparently as a result of an improvement in global status and cognition in placebo recipients in the last weeks of the trial. Initial results of a third study in this patient population, with memantine or placebo added to a stable dose of an acetylcholinesterase inhibitor, indicate a numerical difference that was not significant.

Meta-analyses indicate significant effects of memantine on global status, cognition and function in patients with mild to severe Alzheimer’s disease, and on global status, cognition, function and behaviour in patients with moderate to severe Alzheimer’s disease.

Tolerability

Memantine was generally well tolerated with a good safety profile during clinical trials, most adverse events being of mild or moderate severity. Adverse events were reported by 70% of patients receiving either memantine or placebo, but most were not considered drug related. In pooled analyses, memantine was associated with a higher incidence of dizziness, headache, constipation and somnolence than placebo. Serious adverse events occurred in 12.7% of memantine and 13.8% of placebo recipients.

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Notes

  1. The use of trade names is for identification purposes only and does not imply endorsement.

References

  1. Farlow MR. NMDA receptor antagonists: a new therapeutic approach for Alzheimer’s disease. Geriatrics 2004 Jun; 59(6): 22–7

    PubMed  Google Scholar 

  2. Cummings JL. Alzheimer’s disease. N Engl J Med 2004 Jul 1; 351(1): 56–67

    Article  PubMed  CAS  Google Scholar 

  3. Hebert LE, Scherr PA, Beckett LA, et al. Age-specific incidence of Alzheimer’s disease in a community population. JAMA 1995 May 3; 273(17): 1354–9

    Article  PubMed  CAS  Google Scholar 

  4. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons: higher than previously reported. JAMA 1989 Nov 10; 262(18): 2551–6

    Article  PubMed  CAS  Google Scholar 

  5. Li L, Sengupta A, Haque N, et al. Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration. FEBS Lett 2004 May 21; 566(1–3): 261–9

    Article  PubMed  CAS  Google Scholar 

  6. Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer’s disease. CNS Drug Rev 2003 Fall; 9(3): 275–308

    Article  PubMed  CAS  Google Scholar 

  7. Floden AM, Li S, Combs CK. β-amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor α and NMDA receptors. J Neurosci 2005 Mar 9; 25(10): 2566–75

    Article  PubMed  CAS  Google Scholar 

  8. Cacabelos R, Takeda M, Winblad B. The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer’s disease. Int J Geriatr Psychiatry 1999; 14(1): 3–47

    Article  PubMed  CAS  Google Scholar 

  9. Lipton SA. Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer’s disease and other neurologic disorders. J Alzheimers Dis 2004 Dec; 6 (6 Suppl.): S61–74

    PubMed  CAS  Google Scholar 

  10. Forest Laboratories Inc. Prescribing information: Namenda™ tablets (memantine hydrochloride) [online]. Available from URL: http://www.frx.com/pi/namenda_pi.pdf [Accessed 2005 Feb 15]

  11. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev 2006. CD003154; 2 [online]. Available from URL: http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD003154/pdf_fs.html [Accessed 2006 Jun 6]

  12. Jarvis B, Figgitt D. Memantine. Drugs Aging 2003; 20(6): 465–76

    Article  PubMed  CAS  Google Scholar 

  13. Winblad B, Jelic V. Treating the full spectrum of dementia with memantine. Int J Geriatr Psychiatry 2003 Sep; 18 Suppl. 1: S41–6

    Article  PubMed  Google Scholar 

  14. US Department of Health and Human Services. Memantine approval letter [online]. Oct 2003. Available from: http://www.fda.gov/cder/foi/appletter/2003/21487ltr.pdf [Accessed 2005 Mar].

  15. European Medicines Agency. Ebixa. European Public Assessment Report. [online]. Jul 2002. Available from: http://www.emea.eu.int/humandocs/PDFs/EPAR/ebixa [Accessed 22 Feb 2005].

  16. Danysz W, Parsons CG. The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: preclinical evidence. Int J Geriatr Psychiatry 2003 Sep; 18 Suppl. 1: S23–32

    Article  PubMed  Google Scholar 

  17. Chen H-SV, Pellegrini JW, Aggarwal SK, et al. Open-channel block of N-methyl-D-aspartate responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci 1992 Nov; 12(11): 4427–36

    PubMed  CAS  Google Scholar 

  18. Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist: a review of preclinical data. Neuropharmacology 1999 Jun; 38(6): 735–67

    Article  PubMed  CAS  Google Scholar 

  19. Chen H-SV, Wang YF, Rayudu PV, et al. Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience 1998 Oct; 86(4): 1121–32

    Article  PubMed  CAS  Google Scholar 

  20. Blanpied TA, Boeckman FA, Aizenman E, et al. Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol 1997 Jan; 77(1): 309–23

    PubMed  CAS  Google Scholar 

  21. Parsons CG, Gruner R, Rozental J, et al. Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5- dimethyladamantan). Neuropharmacology 1993 Dec; 32(12): 1337–50

    Article  PubMed  CAS  Google Scholar 

  22. Rammes G, Rupprecht R, Ferrari U, et al. The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT3 receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett 2001 Jun 22; 306(1–2): 81–4

    Article  PubMed  CAS  Google Scholar 

  23. Marvanová M, Lakso M, Pirhonen J, et al. The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Neurosci 2001 Sep; 18(3): 247–58

    Article  PubMed  Google Scholar 

  24. Weller M, Finiels-Marlier F, Paul SM. NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine. Brain Res 1993 Jun 4; 613(1): 143–8

    Article  PubMed  CAS  Google Scholar 

  25. Erdö SL, Schäfer M. Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate. Eur J Pharmacol 1991 Jun 6; 198(2–3): 215–7

    Article  PubMed  Google Scholar 

  26. Krieglstein J, Lippert K, Pöch G. Apparent independent action of nimodipine and glutamate antagonists to protect cultured neurons against glutamate-induced damage. Neuropharmacology 1996; 35(12): 1737–42

    Article  PubMed  CAS  Google Scholar 

  27. Pellegrini JW, Lipton SA. Delayed administration of memantine prevents N-methyl-D-aspartate receptor-mediated neurotoxicity. Ann Neurol 1993 Apr; 33(4): 403–7

    Article  PubMed  CAS  Google Scholar 

  28. Seif el Nasr M, Peruche B, Rossberg C, et al. Neuroprotective effect of memantine demonstrated in vivo and in vitro. Eur J Pharmacol 1990 Aug 21; 185(1): 19–24

    Article  Google Scholar 

  29. Wenk GL, Zajaczkowski W, Danysz W. Neuroprotection of acetylcholinergic basal forebrain neurons by memantine and neurokinin B. Behav Brain Res 1997 Feb; 83(1–2): 129–33

    Article  PubMed  CAS  Google Scholar 

  30. Heim C, Sontag KH. Memantine prevents progressive functional neurodegeneration in rats. J Neural Transm 1995; 46 Suppl.: 117–30

    CAS  Google Scholar 

  31. Miguel-Hidalgo JJ, Alvarez XA, Cacabelos R, et al. Neuroprotection by memantine against neurodegeneration induced by β-amyloid(1–40). Brain Res 2002 Dec 20; 958(1): 210–21

    Article  PubMed  CAS  Google Scholar 

  32. Minkeviciene R, Banerjee P, Tanila H. Memantine improves spatial learning in a transgenic mouse model of Alzheimer’s disease. J Pharmacol Exp Ther 2004 Jun 10; 311(2): 677–82

    Article  PubMed  CAS  Google Scholar 

  33. Potkin SG, McDonald S, Gergel I, et al. Memantine monotherapy increases brain metabolism (PET) and effectively treats mild to moderate Alzheimer’s disease [abstract no. P02.292]. 24th Collegium Internationale Neuro-Psychopharmacologicum Congress; 2004 Jun 20–24; Paris. Int J Neuropsychopharmacol 2004; 7 (Suppl. 1): S380–1.

    Google Scholar 

  34. Schugens MM, Egerter R, Daum I, et al. The NMDA antagonist memantine impairs classical eyeblink conditioning in humans. Neurosci Lett 1997 Mar 7; 224(1): 57–60

    Article  PubMed  CAS  Google Scholar 

  35. Rammsayer TH. Effects of pharmacologically induced changes in NMDA-receptor activity on long-term memory in humans. Learn Mem 2001; 8(1): 20–5

    Article  PubMed  CAS  Google Scholar 

  36. Schwenkreis P, Witscher K, Janssen F, et al. Influence of the N-methyl-D-aspartate antagonist memantine on human motor cortex excitability. Neurosci Lett 1999 Aug 6; 270(3): 137–40

    Article  PubMed  CAS  Google Scholar 

  37. Dinse HR, Ragert P, Pleger B, et al. Pharmacological modulation of perceptual learning and associated cortical reorganization. Science 2003 Jul 4; 301(5629): 91–4. Plus supporting material [online]. Available from URL: http://www.sciencemag.org/cgi/data/301/5629/91/DC1/ [Accessed 2005 Feb 15]

    Article  PubMed  CAS  Google Scholar 

  38. Schulz H, Jobert M, Coppola R, et al. The use of diurnal vigilance changes in the EEG to verify vigilance-enhancing effects of memantine in a clinical pharmacological study. Neuropsychobiology 1996; 33(1): 32–40

    Article  PubMed  CAS  Google Scholar 

  39. Tandon V. US Food and Drug Administration Center for Drug Evaluation and Research approval package for application number 21-487. Clinical pharmacology and biopharmaceutics review: memantine [online]. Available from URL: http://www.fda.gov/cder/foi/nda/2003/21-487_Namenda.htm [Accessed 2005 Feb 18]

  40. Wesemann W, Sturm G, Funfgeld EW. Distribution of metabolism of the potential anti-Parkinson drug memantine in the human. J Neural Transm Suppl 1980; (16): 143-8

  41. Kornhuber J, Quack G. Cerebrospinal fluid and serum concentrations of the N-methyl-D-aspartate (NMDA) receptor antagonist memantine in man. Neurosci Lett 1995 Aug 4; 195(2): 137–9

    Article  PubMed  CAS  Google Scholar 

  42. Periclou A, Ventura D, Rao N, et al. Pharmacokinetic study of memantine in healthy and renally impaired subjects. Clin Pharmacol Ther 2006 Jan; 79(1): 134–43

    Article  PubMed  CAS  Google Scholar 

  43. Micuda S, Mundlova L, Anzenbacherova E, et al. Inhibitory effects of memantine on human cytochrome P450 activities: prediction of in vivo drug interactions. Eur J Clin Pharmacol 2004 Oct; 60(8): 583–9

    Article  PubMed  CAS  Google Scholar 

  44. Wenk GL, Quack G, Moebius H-J, et al. No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. Life Sci 2000 Feb 11; 66(12): 1079–83

    Article  PubMed  CAS  Google Scholar 

  45. Periclou AP, Ventura D, Sherman T, et al. Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil. Ann Pharmacother 2004 Sep; 38(9): 1389–94

    Article  PubMed  CAS  Google Scholar 

  46. Forest Laboratories Inc. Forest Laboratories Clinical Trials Registry: study no. MEM-MD-01 [online]. Available from URL: http://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-01_final.pdf [Accessed 2005 Jun 8]

  47. Reisberg B, Doody R, Stöffler A, et al. Memantine in moderateto-severe Alzheimer’s disease. N Engl J Med 2003 Apr 3; 348(14): 1333–41

    Article  PubMed  CAS  Google Scholar 

  48. Winblad B, Graham SM, Lee GS, et al. Efficacy and tolerability of memantine in nursing home patients with moderate-to-severe dementia of the Alzheimer’s type [poster no. 64]. 17th Annual Meeting of the American Association for Geriatric Psychiatry; 2004 Feb 21–24; Baltimore (MD)

  49. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004 Jan 21; 291(3): 317–24

    Article  PubMed  CAS  Google Scholar 

  50. Bakchine S, Pascual-Gangnant L, Loft H. Results of a randomised, placebo-controlled 6-month study in the treatment of mild-to-moderate Alzheimer’s Disease in Europe [poster no. P2087]. 9th Congress of the European Federation of Neurological Societies; 2005 Sep 17–20; Athens

  51. Forest Laboratories Inc. Forest Laboratories Clinical Trials Registry: study no. MEM-MD-12 [online]. Available from URL: http://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-12_final.pdf [Accessed 2005 Jun 8]

  52. Peskind ER, Potkin SG, Pomara N, et al. Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Am J Geriatr Psychiatry 2006 Aug; 14(8): 704–15

    Article  PubMed  Google Scholar 

  53. Doody RS, Tariot PN, Pfeiffer E, et al. Meta-analysis of 6-month memantine clinical trials in Alzheimer’s disease [poster no. 81]. New Clinical Drug Evaluation Unit 45th Annual Meeting; 2005 Jun 6–9; Boca Raton (FL)

  54. Winblad B, Poritis N. Memantine in severe dementia: results of the 9M-BEST study (benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry 1999 Feb; 14(2): 135–46

    Article  PubMed  CAS  Google Scholar 

  55. Winblad B, Möbius HJ, Stöffler A. Glutamate receptors as a target for Alzheimer’s disease — are clinical results supporting the hope? J Neural Transm 2002; 62 Suppl.: 217–25

    CAS  Google Scholar 

  56. LU-99679 protocol, study report (data on file) Denmark: H. Lundbeck, A/S. 2005

  57. Mani RB. US Food and Drug Administration Center for Drug Evaluation and Research approval package for application number 21-487. Medical reviews: memantine [online]. Available from URL: http://www.fda.gov/cder/foi/nda/2003/21-487_Namenda.htm [Accessed 2005 Feb 18]

  58. Tocco M, Olin JT, Feldman HH, for the MEM-MD-02 Study Group. Maintenance of response to memantine treatment in moderate to severe Alzheimer’s disease patients receiving stable donepezil treatment [poster no. 23]. 19th Annual Meeting of the American Association for Geriatric Psychiatry; 2006 Mar 10–13; San Juan

  59. Feldman H, Schmitt FA, Doraiswamy PM, et al. Memantine and individual activities of daily living in moderate to severe Alzheimer’s disease [poster no. P02.092]. 57th Annual Meeting of the American Academy of Neurology; 2005 Apr 9–16; Miami Beach (FL)

  60. Wilkinson D, Andersen HF. Prevention of worsening of clinical symptoms in moderate to severe Alzheimer’s disease in patients treated with memantine [poster]. 9th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy; 2006 April 19–22; Geneva

  61. Winblad B, Jones RW, Wirth Y, et al. Memantine in moderate to severe Alzheimer’s disease: a meta-analysis of randomised clinical trials [poster]. 9th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy; 2006 April 19–22; Geneva

  62. Gauthier S, Wirth Y, Mobius HJ. Effects of memantine on behavioural symptoms in Alzheimer’s disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J Geriatr Psychiatry 2005 Apr 25; 20(5): 459–64

    Article  PubMed  CAS  Google Scholar 

  63. Cummings JL, Schneider E, Tariot PN, et al. Behavioural effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 2006 Jul 11; 67: 57–63

    Article  PubMed  CAS  Google Scholar 

  64. Rive B, Vercelletto M, Damier FD, et al. Memantine enhances autonomy in moderate to severe Alzheimer’s disease. Int J Geriatr Psychiatry 2004 May; 19(5): 458–64

    Article  PubMed  Google Scholar 

  65. Livingston G, Katona C. The place of memantine in the treatment of Alzheimer’s disease: a number needed to treat analysis. Int J Geriatr Psychiatry 2004 Sep 27; 19(10): 919–25

    Article  PubMed  Google Scholar 

  66. Reisberg B, Doody R, Stoffler A, et al. A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Arch Neurol 2006 Jan; 63(1): 49–54

    Article  PubMed  Google Scholar 

  67. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984 Jul; 34(7): 939–44

    Article  PubMed  CAS  Google Scholar 

  68. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th Ed. (DSM-IV). Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  69. Plosker GL, Lyseng-Williamson KA. Memantine: a pharmacoeconomic review of its use in moderate-to-severe Alzheimer’s disease. Pharmacoeconomics 2005; 23(2): 193–206

    Article  PubMed  Google Scholar 

  70. Jönsson L. Cost-effectiveness of memantine for moderate to severe Alzheimer’s disease in Sweden. Am J Geriatr Pharmacother 2005 Jun; 3(2): 77–86

    Article  PubMed  Google Scholar 

  71. National Institute for Clinical Excellence. Appraisal Consultation Document: Alzheimer’s disease — donepezil, rivastigmine, galantamine and memantine (review) [online]. Available from URL: http://www.nice.org.uk/page.aspx?o=245912 [Accessed 2005 Mar 1]

  72. Neumann PJ. Health utilities in Alzheimer’s disease and implications for cost-effectiveness analysis. Pharmacoeconomics 2005; 23(6): 537–41

    Article  PubMed  Google Scholar 

  73. Loveman E, Green C, Kirby J, et al. The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer’s disease. Health Technol Assess 2006 Jan; 10(1): 1–176

    Google Scholar 

  74. Kirby J, Green C, Loveman E, et al. A systematic review of the clinical and cost-effectiveness of memantine in patients with moderately severe to severe Alzheimer’s disease. Drugs Aging 2006; 23(3): 227–40

    Article  PubMed  CAS  Google Scholar 

  75. Francois C, Sintonen H, Sulkava R, et al. Cost effectiveness of memantine in moderately severe to severe Alzheimer’s disease: a Markov model in Finland. Clin Drug Investig 2004; 24(7): 373–84

    Article  PubMed  CAS  Google Scholar 

  76. Jones RW, McCrone P, Guilhaume C. Cost effectiveness of memantine in Alzheimer’s Disease: an analysis based on a probabilistic Markov model from a UK perspective. Drugs Aging 2004; 21(9): 607–20

    Article  PubMed  CAS  Google Scholar 

  77. European Medicines Agency. European Public Assessment Report: procedural steps taken and scientific information after authorisation [online]. Available from URL: http://www.emea.eu.int/humandocs/Humans/EPAR/ebixa/ebixa.htm [Accessed 2006 Jun 22]

  78. European Medicines Agency. Ebixa. European Public Assessment Report: summary of product characteristics. [online]. Available from URL: http://www.emea.eu.int/humandocs/Humans/EPAR/ebixa/ebixa.htm [Accessed 2006 Jul 25]

  79. Merz Pharmaceuticals. Summary of product characteristics. Axura 10 mg film coated tablets [online]. Available from URL: http://download.merz.de/axura-info/pdf/memantine_product_characteristics.pdf#page=9 [Accessed 2006 May 1]

  80. Wimo A, Winblad B, Aguero-Torres H, et al. The magnitude of dementia occurrence in the world. Alzheimer Dis Assoc Disord 2003 Apr–Jun; 17(2): 63–7

    Article  PubMed  Google Scholar 

  81. Wimo A, Winblad B, Stöffler A, et al. Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer’s disease. Pharmacoeconomics 2003; 21(5): 327–40

    Article  PubMed  CAS  Google Scholar 

  82. Maslow K, Selstad J, Denman SJ. Guidelines and care management issues for people with Alzheimer’s disease and other dementias. Dis Manage Health Outcomes 2002; 10(11): 693–706

    Article  Google Scholar 

  83. Johnson N, Davis T, Bosanquet N. The epidemic of Alzheimer’s disease. How can we manage the costs? Pharmacoeconomics 2000 Sep; 18(3): 215–23

    CAS  Google Scholar 

  84. Bloom BS, de Pouvourville N, Straus WL. Cost of illness of Alzheimer’s disease: how useful are current estimates? Gerontologist 2003 Apr; 43(2): 158–64

    Article  PubMed  Google Scholar 

  85. Small GW, Rabins PV, Barry PP, et al. Diagnosis and treatment of Alzheimer disease and related disorders: consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA 1997 Oct 22–29; 278(16): 1363–71

    Article  PubMed  CAS  Google Scholar 

  86. Smith GB. Case management guideline: Alzheimer disease and other dementias. Lippincotts Case Manag 2002 Mar–Apr; 7(2): 77–84

    Article  PubMed  Google Scholar 

  87. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health 1998 Sep; 88(9): 1337–42

    Article  PubMed  CAS  Google Scholar 

  88. Grossberg GT, Desai AK. Management of Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 2003 Apr; 58(4): 331–53

    Article  PubMed  Google Scholar 

  89. Cummings JL, Frank JC, Cherry D, et al. Guidelines for managing Alzheimer’s disease: part I. Assessment. Am Fam Physician 2002 Jun 1; 65(11): 2263–72

    Google Scholar 

  90. Cummings JL, Frank JC, Cherry D, et al. Guidelines for managing Alzheimer’s disease: part II. Treatment. Am Fam Physician 2002 Jun 15; 65(12): 2525–34

    Google Scholar 

  91. Rogers SL, Doody RS, Mohs RC, et al. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Arch Intern Med 1998 May 11; 158(9): 1021–31

    CAS  Google Scholar 

  92. Feldman H, Gauthier S, Hecker J, et al. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology 2001 Aug 28; 57(4): 613–20

    Article  PubMed  CAS  Google Scholar 

  93. Doraiswamy PM. Non-cholinergic strategies for treating and preventing Alzheimer’s disease. CNS Drugs 2002; 16(12): 811–24

    Article  PubMed  CAS  Google Scholar 

  94. Roses AD, Pangalos MN. Drug development and Alzheimer disease. Am J Geriatr Psychiatry 2003; 11(2): 123–30

    PubMed  Google Scholar 

  95. Windisch M, Hutter-Paier B, Schreiner E. Current drugs and future hopes in the treatment of Alzheimer’s disease. J Neural Transm 2002; 62 Suppl.: 149–64

    CAS  Google Scholar 

  96. Michaelis ML. Drugs targeting Alzheimer’s disease: some things old and some things new. J Pharmacol Exp Ther 2003; 304(3): 897–904

    Article  PubMed  CAS  Google Scholar 

  97. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997 Apr 24; 336(17): 1216–22

    CAS  Google Scholar 

  98. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005 Jun 9; 352(23): 2379–88

    Article  PubMed  CAS  Google Scholar 

  99. Orgogozo JM, Gilman S, Dartigues JF, et al. Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization. Neurology 2003 Jul 8; 61(1): 46–54

    Article  PubMed  CAS  Google Scholar 

  100. Wilcock G, Möbius HJ, Stöffler A. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol 2002 Nov; 17(6): 297–305

    Article  PubMed  CAS  Google Scholar 

  101. Orgogozo JM, Rigaud AS, Stöffler A, et al. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke 2002 Jul; 33(7): 1834–9

    Article  PubMed  CAS  Google Scholar 

  102. Möbius HJ, Stoffler A. New approaches to clinical trials in vascular dementia: memantine in small vessel disease. Cerebrovasc Dis 2002; 13 Suppl. 2: 61–6

    Article  PubMed  Google Scholar 

  103. Pass MD, Shua-Haim JR, Patel P, et al. Safety, tolerability, and caregiver’s impressions of combination therapy with galantamine and memantine for the treatment of Alzheimer’s disease [abstract no. P1-392]. 9th International Conference on Alzheimer’s Disease and Related Disorders; 2004 Jul 17–22; Philadelphia (PA)

  104. Shua-Haim JR, Pass MD, Patel S, et al. Safety, tolerability, and caregiver’s impressions of combination therapy with rivastigmine and memantine for the treatment of Alzheimer’s disease [abstract no. P1-377]. 9th International Conference on Alzheimer’s Disease and Related Disorders; 2004 Jul 17–22; Philadelphia (PA)

  105. US National Institutes of Health. An evaluation of the safety and efficacy of memantine in agitated patients with moderate to severe Alzheimer’s disease [online]. Available from URL: http://www.clinicaltrials.gov/ct/show/NCT00097916 [Accessed 2005 Mar 4]

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Various sections of the manuscript reviewed by: S. Bleich, Klinik mit Poliklinik für Psychiatrie und Psychotherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; R. Cacabelos, EuroEspes Biomedical Research Center, Santa Marta de Babio, La Coruna, Spain; M.R. Farlow, Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA; R. McShane, Cochrane Dementia and Cognitive Improvement Group, Fulbrook Centre, Churchill Hospital, Oxford, England; J.J. Miguel-Hidalgo, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA; F.A. Schmitt, Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky Medical Center, Lexington, Kentucky, USA; R.R. Tampi, Geriatric Services, Yale New Haven Psychiatric Hospital, New Haven, Connecticut, USA; C.H. van Dyck, Department of Psychiatry and Neurobiology, Yale University, New Haven, Connecticut, USA; G.L. Wenk, Departments of Psychology and Neurology, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, Arizona, USA; A. Wimo, Aging Research Centre, Neurotec Department, Karolinska Institutet, Stockholm, Sweden.

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Sources: Medical literature published in any language since 1980 on memantine, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information and unpublished contributory data was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘memantine’. Searches last updated 7 August 2006.

Selection: Studies in patients with Alzheimer’s disease who received memantine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled, peer reviewed trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Memantine, Alzheimer’s disease, dementia, pharmacodynamics, pharmacokinetics, therapeutic use.

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Robinson, D.M., Keating, G.M. Memantine. Drugs 66, 1515–1534 (2006). https://doi.org/10.2165/00003495-200666110-00015

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