Tacrine
|
Davis et al, 199236 | Not stated; 632 enrolled in “enrichment” phase | 112 placebo | 401 unable to calculate a “best dose” | 6 week titration phase | MMSE, PDS, PSMS, IADL, ADAS-Noncog, ADAS-total | Included a pretest “enrichment phase” (n = 632) to determine whether each patient had a “best dose” response (n = 231) |
| | 103 “best dose” (40 mg or 80 mg) | 16 did not enter the double blind phase | 2 week placebo baseline phase | | Global measure: GCIC |
| | | | 6 weeks double blind phase | | |
| | | | 6 weeks open label phase | | |
Knapp et al, 199437 | Not stated | 184 placebo | 59 placebo | 24 week titration phase | MMSE, PDS, GDS, Caregiver CGIC, IADL, FCCA, ADAS-total, ADAS-Noncog, PSMS | Global measure: CIBI |
| | 61 80 mg/d | 32 80 mg/d | 6 week double blind phase | | |
| | 179 120 mg/d | 121 120 mg/d | | | |
| | 239 160 mg/d | 172 160 mg/d | | | |
Metrifonate
|
Becker et al, 199626 | 53:51 | 23 placebo | 1 metrifonate | 3 week placebo run-in | MMSE, ADLC, ADAS-cog, ADAS-total | Included a 3 week loading dose followed by a 9 week maintenance dose |
| | 27 2.1 mg/kg | | 3 month double blind phase | | Global measure: GIS |
| | weekly dose | | Final open label phase | | |
Cummings et al, 199827 | Not stated | 120 placebo | | 2 week screening 12 week double blind phase | PSMS, MMSE, IADL, CIBIS+, GERRI | Included a 2 week loading dose followed by a 10 week maintenance dose |
| | 121 0.2 mg/kg/d | | 40 week optional open label phase | | Global measure: CIBIC+ |
| | 120 0.3 mg/kg/d | | | | |
| | 119 0.65 mg/kg/d | | | | |
Morris et al, 199828 | 511:408 | 135 placebo | 16 placebo | 2 week screening | MMSE, NPI, GDS, ADAS-Noncog, CIBIS+, DAD | Included a 2 week loading dose followed by a 24 week maintenance dose |
| | 273 0.65 mg/kg/d | 58 0.65 mg/kg/d | 26 week double blind phase | | Global measure: CIBIC+ |
| | | | 8 week post treatment | | |
Donepezil
|
Rogers et al, 199621 | Not stated | 40 placebo | 5 placebo | 12 week double blind | MMSE, ADL, CDR-SB, QoL-P, QoL-C | Global measure: CGIC |
| | 42 1 mg/d | 8 1 mg/d | 2 week placebo washout phase | | |
| | 40 3 mg/d | 2 3 mg/d | | | |
| | 39 5 mg/d | 5 5 mg/d | | | |
Rogers et al, 1998a23 | Not stated | 162 placebo | N/A | 24 week double blind phase | MMSE, CDR-SB, QoL | Global measure: CIBIC+ |
| | 154 5 mg/d | | 6 week placebo washout phase | | |
| | 157 10 mg/d | | | | |
Rogers et al, 1998b22 | Not stated | 153 placebo | N/A | 12 week double blind phase | MMSE, CDR-SB, QoL | Global measures: CIBIC+ |
| | 157 5 mg/d | | 3 week single blind washout | | |
| | 158 10 mg/d | | | | |
Homma et al, 200024 | Not stated | 134 placebo | 39 withdrawals | 24 week double blind study | CDR-SB, CMCS, MENFIS | ADAS-J Cog—Japanese version of the ADAS-Cog |
| | 134 5 mg/d | | | | Global measure: J-CGIC |
Burns et al, 199925 | Not stated | 274 placebo | N/A | 24 week double blind phase | IDDD, CDR-SB, QoL | Global measure: CIBIC+ |
| | 271 5 mg/d | | 6 week placebo washout phase | | |
| | 273 10 mg/d | | | | |
Rivastigmine
|
Rösler et al, 199930 | 831:725 | 239 placebo | 31 placebo | 26 weeks | PDS, GDS, MMSE | Global measure: CIBIC+ |
| | 243 1–4 mg/d | 33 1–4 mg/d | | | |
| | 243 6–12 mg/d | 79 6–12 mg/d | | | |
Corey-Bloom et al, 199829 | 925:699 | 235 placebo | 38 placebo | 7 week titration phase | PDS, MMSE, GDS | Global measure: CIBIC+ |
| | 233 1–4 mg/d | 34 1–4 mg/d | 19 week flexible dose phase | | |
| | 231 6–12 mg/d | 82 6–12 mg/d | | | |
Galantamine
|
Tariot et al, 200031 | 1178:978 | 286 placebo | 46 placebo | 4 week placebo run-in phase | ADCS/ADL, NPI | Global measure: CIBIC+ |
| | 140 8 mg/d | 32 8 mg/d | 5 month double blind phase | | |
| | 279 16 mg/d | 60 16 mg/d | | | |
| | 273 24 mg/d | 61 24 mg/d | | | |
Raskind et al, 200032 | 764:636 | 213 placebo | 41 placebo | 4 week placebo run-in phase | ADL, DAD | Global measure: CIBIC+ |
| | 212 24 mg/d | 68 24 mg/d | 6 month double blind phase | | |
| | 211 32 mg/d | 89 32 mg/d | | | |
Rockwood et al, 200134 | 534:386 | 125 placebo | 12 placebo | 4 week placebo run-in period | NPI, ADAS-Noncog, DAD, PSQI | Global measure: CIBIC+ |
| | 261 24–32 mg/d | 86 24–32 mg/d | 3 month double blind phase | | |
Wilcock et al, 200033 | 753:653 | 215 placebo | 29 placebo | 4 week placebo run-in period | DAD, 13-item ADAS-Cog, MMSE | Global measure: CIBIC+ |
| | 220 24 mg/d | 44 24 mg/d | 5 month double blind phase | | |
| | 218 32 mg/d | 55 32 mg/d | | | |
Wilkinson et al 200135 | Not stated | 87 placebo | 14 placebo | 2 week placebo run-in | PDS-1 | Global measure: CGIC |
| | 88 18 mg/d | 25 18 mg/d | 2 week dose escalation | | |
| | 56 24 mg/d | 14 24 mg/d | 10 weeks on assigned dose | | |
| | 54 36 mg/d | 26 36 mg/d | | | |
Physostigmine
|
Van Dyck et al, 200040 | Not stated | 93 placebo | 11 placebo | 3 week dose enrichment phase | MMSE, IADL, GCIC | Global measure: CIBIC+ |
| | 83 best dose | 17 best dose | 4 week placebo washout phase | | |
| | | | 12 week double blind phase | | |
Thal et al, 199639 | 1111:366 | 183 placebo | N/A | 4 week dose titration phase | MMSE, PSMS, IADL | Global measure: CGIC |
| | 183 best dose | | 2 week all placebo phase | | |
| | | | 6 week double blind phase | | |
Thal et al, 199938 | 699:475 | 117 placebo | 31 placebo | 2 week washout period | IADL, GERRI, CGIC | Global measure: CIBIC+ |
| | 176 30 mg/d | 110 30 mg/d | 9 week dose titration phase | | |
| | 182 36 mg/d | 124 36 mg/d | 24 week double blind phase | | |