Abstract
Background: Galantamine (hydrobromide), a reversible acetylcholinesterase inhibitor and allosteric nicotinic receptor modulator, slows cognitive and functional decline in mild to moderate dementia of the Alzheimer’s type. Although several drugs are indicated for mild to moderate Alzheimer’s disease (AD), no published study has separately analysed mild and moderate AD subgroups to assess the effect of dosage.
Objective: To compare the efficacy and safety of galantamine 16 and 24 mg/day in patient subgroups with mild or moderate AD.
Methods: This post hoc analysis (n = 838) of a 5-month, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of galantamine 16 and 24 mg/day in a subgroup of patients with mild AD (Mini-Mental State Examination [MMSE] >18) and a subgroup with moderate AD (MMSE 10–18). Efficacy outcomes included the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) score and treatment response (ADAS-cog maintenance [≥0-point improvement], improvement ≥4 points and improvement ≥7 points).
Results: Mean ADAS-cog scores of patients with mild AD demonstrated significant improvement from baseline with galantamine 16 and 24 mg/day (p < 0.001 for both), whereas cognitive function did not change significantly for placebo recipients (p = 0.559). Patients with moderate AD improved with galantamine 24 mg/day (p = 0.009) but not with 16 mg/day (p = 0.768); a decline occurred with placebo (p < 0.001). A greater proportion of patients treated with galantamine 16 mg/day (76% and 52% for mild and moderate AD, respectively) or 24 mg/day (69% and 61%, respectively) demonstrated a treatment response (i.e. ADAS-cog was maintained or improved) relative to placebo (55% and 28%, respectively; p < 0.05). Patients with moderate AD trended toward greater response with the 24 mg/day dosage than with the 16 mg/day dosage. Galantamine was well tolerated. Adverse events were comparable for all study groups with mild or moderate AD.
Conclusion: This post hoc analysis suggests that galantamine 16 mg/day is the optimal dosage for patients with mild AD, as similar efficacy is observed with the 24 mg/day dose. However, patients with moderate AD appear to gain additional benefit from galantamine 24 mg/day.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–7
Herbert LE, Scherr PA, Bienias JL, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 2003; 60: 1119–22
Alzheimer’s Association. Alzheimer’s facts and figures 2007 [online]. Available from URL: http://www.alz.org/national/documents/report_alzfactsfigures2007.pdf [Accessed 2007 Jun 5]
American Psychiatric Association. Practice guidelines for the treatment of patients with Alzheimer’s disease and other dementias late in life. Am J Psychiatry 1997; 154: 1–39
Geldmacher DS. Treatment guidelines for Alzheimer’s disease: redefining perceptions in primary care. Prim Care Companion J Clin Psychiatry 2007; 9: 113–21
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. rev. Washington, DC: American Psychiatric Association, 2000
Forstl H, Kerz A. Clinical features of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 1999; 249: 288–90
Bowie P, Branton T, Holmes J. Should the Mini Mental State Examination be used to monitor dementia treatment? Lancet 1999; 354: 1527–8
Galasko DR, Gould RL, Abramson IS, et al. Measuring cognitive change in a cohort of patients with Alzheimer’s disease. Stat Med 2000; 19: 1421–32
Aricept/Aricept ODT [package insert]. Teaneck (NJ): Eisai Co., Ltd, 2006
Cognex [package insert]. Rosewell (GA): First Horizon Pharmaceutical Corp., 2002
Exelon [package insert]. East Hanover (NJ): Novartis Pharmaceuticals Corp., 2006
Reminyl [summary of product characteristics]. Dublin, Ireland: Shire Pharmaceuticals Ireland Limited, 2007
Reminyl XL [summary of product characteristics]. Dublin, Ireland: Shire Pharmaceuticals Ireland Limited, 2007
Razadyne ER/Razadyne [package insert]. Titusville (NJ): Ortho-McNeil Neurologics Inc., 2006
Ebixa [summary of product characteristics]. Valby, Denmark: H. Lundbeck A/S, 2005
Axura [summary of product characteristics]. Frankfurt, Germany: Merz Pharmaceuticals GmbH, 2005
Namenda [package insert]. St Louis (MO): Forest Pharmaceuticals Inc., 2005
Samochocki M, Zerlin M, Jostock R, et al. Galantamine is an allosterically potentiating ligand of the human α4/β2 nAChR. Acta Neurol Scand 2000; 176: 68–73
Maelicke A, Samochocki M, Jostock R, et al. Allosteric sensitization of nicotinic receptors by galantamine, a new treatment strategy for Alzheimer’s disease. Biol Psychiatry 2001; 49: 279–88
Raskind MA, Peskind ER, Wessel T, et al. Galantamine in AD: a 6-month randomized, placebo controlled trial with a 6-month extension. Neurology 2000; 54: 2261–8
Rockwood K, Mintzer J, Truyen L, et al. Effects of a flexible galantamine dose in Alzheimer’s disease: a randomized, controlled trial. J Neurol Neurosurg Psychiatry 2001; 71: 589–95
Tariot PN, Solomon PR, Morris JC, et al. A 5-month, randomized, placebo-controlled trial of galantamine in AD. Neurology 2000; 54: 2269–76
Wilcock GK, Lillienfeld S, Gaens E, on behalf of the Galantamine International-1 Study Group. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer’s disease: a multicentre randomized controlled trial. BMJ 2000; 321: 1445–9
Wilkinson D, Murray J, in collaboration with the Galantamine Research Group. Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 2001; 16: 852–7
Rosen WG, Mohs RC, Davis Kl. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984; 141: 1356–64
Schneider LS, Olin JT, Doody RS, et al. Validity and reliability of the Alzheimer’s Disease Cooperative Study: Clinical Global Impression of Change. Alzheimer Dis Assoc Disorder 1997; 11Suppl. 2: S22–32
Schwalen S, Van Baelen B, Kavanagh S. Comparison of the effects of 24 mg versus 16mg galantamine in patients with moderate Alzheimer’s disease [poster presentation]. 3rd Congress of the European Union of Geriatric Medicine Societies (EUGMS); 2004 Sep 15–18; Vienna
Davis KL, Mohs RC, Marlin D, et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA 1999 Apr 21; 281(15): 1401–6
Acknowledgements
This study was funded by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Titusville, NJ, USA. All authors made significant contributions to the design of the trial protocol, analysis of the data and writing of the manuscript. The manuscript was reviewed and finalized by all of the authors. Dr Stephen Aronson has served as a consultant to and/or received honoraria from Johnson & Johnson, Pfizer, Novartis, Forest and Myriad, and has received research grants from Janssen, Novartis, Forest, Myriad and Neurochem. Bart Van Baelen is an employee of SGS Life Science Services. Shane Kavanagh is an employee of Janssen Pharmaceutica and holds stock in Johnson & Johnson. Susanne Schwalen was previously an employee of Janssen-Cilag. The authors acknowledge the contribution of Oxford PharmaGenesis in providing editorial assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aronson, S., Van Baelen, B., Kavanagh, S. et al. Optimal Dosing of Galantamine in Patients with Mild or Moderate Alzheimer’s Disease. Drugs Aging 26, 231–239 (2009). https://doi.org/10.2165/00002512-200926030-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002512-200926030-00004