Drug Treatments for Alzheimer’s Technology Disease. I. A Comparative Analysis of Report Clinical Trials Issue 8 May 2000 Publications can be requested from: CCOHTA 110-955 Green Valley Crescent Ottawa, Ontario, Canada, K2C 3V4 Tel. (613) 226-2553 Fax. (613) 226-5392 Email: [email protected] or download from CCOHTA’s web site: http://www.ccohta.ca Cite as: Wolfson C, Moride Y, Perrault A, Momoli F, Demers L, Oremus M. Drug treatments for Alzheimer’s disease. I. A comparative analysis of clinical trials. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); 2000. Reproduction of this document for non-commercial purposes is permitted provided appropriate credit is given to CCOHTA. Legal Deposit - 2000 National Library of Canada ISBN 1-895561-78-7 (Set) ISBN 1-895561-82-5 (Part 1) Publications Mail Agreement Number: 1633171 Canadian Coordinating Office for Health Technology Assessment Drug Treatments for Alzheimer’s Disease. I. A Comparative Analysis of Clinical Trials Christina Wolfson, PhD1,2 Yola Moride, PhD1,3 Anne Perrault, MSc1 Franco Momoli, MSc1,2 Louise Demers, PhD1 Mark Oremus, MA1,2 May 2000 Technical assistance provided by: Carole Bohbot, Irina Lazariciu, Alexander Tsertsvadze 1. Centre for Clinical Epidemiology and Community Studies, S.M.B.D. Jewish General Hospital, Montréal, Québec 2. Joint Departments of Epidemiology & Biostatistics and Occupational Health, McGill University, Montréal, Québec 3. Faculté de Pharmacie, Université de Montréal, , Montréal, Québec TABLE OF CONTENTS REVIEWERS AND ACKNOWLEDGMENTS .........................................................................................1 EXECUTIVE SUMMARY ..........................................................................................................................2 1 INTRODUCTION...............................................................................................................................4 1.1 INTRODUCTION.................................................................................................................................. 4 1.2 OBJECTIVES....................................................................................................................................... 5 1.3 EFFICACY/EFFECTIVENESS ................................................................................................................ 5 1.4 BEST EVIDENCE SYNTHESIS .............................................................................................................. 5 1.5 RESEARCH GROUP............................................................................................................................. 6 2 METHODS ..........................................................................................................................................7 2.1 MEDICATIONS FOR ALZHEIMER’S DISEASE ....................................................................................... 7 2.2 SEARCH STRATEGY ........................................................................................................................... 7 2.2.1 PERUSE - McGill University.................................................................................................. 8 2.2.2 Cochrane Library.................................................................................................................... 8 2.2.3 Review Articles........................................................................................................................ 8 2.2.4 Multi-Media ............................................................................................................................ 8 2.3 RESULTS............................................................................................................................................ 8 2.3.1 Selection of Trials for Review ................................................................................................. 9 3 METHODOLOGICAL DESCRIPTION AND BEST EVIDENCE SYNTHESIS OF THE ANTIDEMENTIA TRIALS.......................................................................................................................12 3.1 INTRODUCTION................................................................................................................................12 3.2 DONEPEZIL...................................................................................................................................... 13 3.2.1 Methods................................................................................................................................. 13 3.2.2 Results................................................................................................................................... 15 3.3 METRIFONATE................................................................................................................................. 20 3.3.1 Methods................................................................................................................................. 20 3.3.2 Results................................................................................................................................... 23 3.4 RIVASTIGMINE ................................................................................................................................26 3.4.1 Methods................................................................................................................................. 26 3.4.2 Results................................................................................................................................... 29 3.5 SELEGILINE AND VITAMIN E ........................................................................................................... 33 3.5.1 Methods................................................................................................................................. 33 3.5.2 Results................................................................................................................................... 38 3.5.3 Alpha-tocopherol (vitamin E) ...............................................................................................46 3.6 LECITHIN......................................................................................................................................... 47 3.6.1 Methods................................................................................................................................. 48 3.6.2 Results................................................................................................................................... 49 3.7 PROPENTOFYLLINE.......................................................................................................................... 50 3.7.1 Methods................................................................................................................................. 51 3.7.2 Results................................................................................................................................... 51 3.8 LINOPIRDINE ................................................................................................................................... 53 3.8.1 Methods................................................................................................................................. 54 3.8.2 Results................................................................................................................................... 54 3.9 GINKGO BILOBA (EGB 761) ............................................................................................................ 56 3.9.1 Methods................................................................................................................................. 57 3.9.2 Results................................................................................................................................... 59 3.10 ADVERSE EFFECTS ..................................................................................................................... 68 i 4 SUMMARY OF RESULTS OF THE BEST EVIDENCE SYNTHESIS......................................80 4.1 DONEPEZIL...................................................................................................................................... 83 4.2 METRIFONATE................................................................................................................................. 85 4.3 RIVASTIGMINE ................................................................................................................................86 4.4 GINKGO BILOBA.............................................................................................................................. 87 4.5 FINAL THOUGHTS............................................................................................................................ 88 5 REFERENCE LIST ..........................................................................................................................90 6 BIBLIOGRAPHY BY AUTHOR ..................................................................................................102 APPENDIX A............................................................................................................................................114 APPENDIX B ............................................................................................................................................116 BIBLIOGRAPHY OF EXCLUDED RCTS ..........................................................................................