Donepezil, rivastigmine, galantamine and memantine for ...

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64 Clinical effectiveness TABLE 31 Adverse events for galantamine (note that p-values are not reported unless stated) (cont’d) Wilkinson et al. 66 Proportion reported by ≥ 5% of participants (%) Galantamine 24–32 mg/day (n = 261) Placebo (n = 125) Nausea 13 Not reported Vomiting 6 Not reported Dizziness 5 Not reported Serious adverse events 8 6 [Commercial/academic confidential information removed] Raskind et al. 61 No. (%) of adverse events occurring at least 5% more with any galantamine than placebo Galantamine 24 mg/day Galantamine 32 mg/day Placebo (n = 213) (n = 212) (n = 211) Nausea 79 (37.3) 92 (43.6) 28 (13.1) Vomiting 44 (20.8) 54 (25.6) 16 (7.5) Dizziness 29 (13.7) 39 (18.5) 24 (11.3) Diarrhoea 26 (12.3) 41 (19.4) 21 (9.9) Anorexia 29 (13.7) 43 (20.4) 12 (5.6) Weight loss 26 (12.3) 23 (10.9) 10 (4.7) Abdominal pain 14 (6.6) 23 (10.9) 9 (4.2) Tremor 11 (5.2) 7 (3.3) 1 (0.5) Any adverse event 195 (92.0) 195 (92.4) 168 (78.9) Wilcock et al. 64 No. (%) of adverse events occurring at least 5% more with galantamine than placebo Galantamine 24 mg/day Galantamine 32 mg/day Placebo (n = 215) (n = 220) (n = 218) Nausea 82 (37) 87 (40) 26 (12) Vomiting 45 (20) 37 (17) 9 (4) Diarrhoea 16 (7) 29 (13) 16 (7) Dizziness 24 (11) 26 (12) 10 (5) Headache 21 (10) 25 (11) 7 (3) Anorexia 22 (10) 23 (11) 0 Weight loss 17 (8) 11 (5) 1 (0.5) Any adverse event 182 (83) 194 (89) 165 (77) Tariot et al. 63 No. (%) of adverse events occurring at least 5% more with any galantamine than placebo Galantamine Galantamine Galantamine Placebo (n = 286) 8 mg/day (n = 140) 16 mg/day (n = 279) 24 mg/day (n = 273) Nausea 8 (5.7) 37 (13.3) 45 (16.5) 13 (4.5) Vomiting 5 (3.6) 17 (6.1) 27 (9.9) 4 (1.4) Anorexia 8 (5.7) 18 (6.5) 24 (8.8) 9 (3.1) Agitation 21 (15.0) 28 (10.0) 22 (8.1) 27 (9.4) Diarrhoea 7 (5.0) 34 (12.2) 15 (5.5) 17 (5.9) Any adverse event 106 (75.7) 206 (73.8) 219 (80.2) 206 (72.0) Any serious adverse event 14 (10.0) 28 (10.0) 35 (12.8) 31 (10.8) Deaths 1 (0.7) 3 (1.1) 3 (1.1) 4 (1.4) Wilkinson and Murray65 No. (%) reported by ≥ 5% of participants Galantamine Galantamine Galantamine Placebo (n = 87) 18 mg/day (n = 88) 24 mg/day (n = 56) 36 mg/day (n = 54) Vomiting 15 (17.0) 4 (7.1) 9 (16.7) 4 (4.6) Nausea 15 (17.0) 10 (17.9) 20 (37.0) 3.(3.4) Headache 5 (5.7) 6 (10.7) 8 (14.8) 4 (4.6) Diarrhoea 2 (2.3) 3 (5.4) 2 (3.7) 2 (2.3) Decreased appetite 5 (5.7) 2 (3.6) 4 (7.4) 2 (2.3) Dizziness 4 (4.5) 2 (3.6) 4 (7.4) 3 (3.4) Any adverse event 49 (55.7) 33 (58.9) 38 (70.4) 38 (43.7) Any serious adverse event 6 (6.8) 0 (0.0) 5 (9.3) 3 (3.4)
TABLE 32 Withdrawals due to adverse events for galantamine [Commercial/academic confidential information removed] Raskind et al. 61 were higher among galantamine participants [range: 6% (8 mg/day)–44% (36 mg/day)] than placebo (range 5–9%) (see Table 32). Three trials 61,63,64 demonstrated differential dropout rates between groups for reasons other than adverse events. However, the pattern of the proportion withdrawing was not consistent; in two included trials the dropout rate was greater in the treatment arms but in another study dropout rate was greater in the placebo arm. In three published trials [commercial/academic confidential information removed] there appeared to be no difference between groups. No statistical analyses were undertaken by the trials. Very few deaths were reported in any of the included studies. Data relating to withdrawals and deaths for the individual trials can be found in Appendix 9. Summary ● Six published multicentre placebo-controlled RCTs assessing doses ranging from 8 to 36 mg/day of galantamine over durations of 3–6 months met the inclusion criteria for the systematic review. The methodological quality and the quality of reporting in the studies were variable. Of the six RCTs, three appeared to limit selection bias, 62,64,65 three provided adequate information to reduce the likelihood of measurement bias 61,63,65 and one appeared to guard against the effects of attrition bias. 64 Five RCTs reported that they were sponsored by the manufacturers. © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 1 Galantamine 24 mg/day (n = 212) Galantamine 32 mg/day (n = 211) Placebo (n = 213) 49/212 (23%) 67/211 (32%) 16/213 (8%) Wilcock et al. 64 Galantamine 24 mg/day (n = 220) Galantamine 32 mg/day (n = 218) Placebo (n = 215) 31/220 (14%) 48/218 (22%) 19/215 (9%) Tariot et al. 63 Galantamine Galantamine Galantamine Placebo (n = 286) 8 mg/day (n = 140) 16 mg/day (n = 279) 24 mg/day (n = 273) 9 19 27 20 Wilkinson and Murray65 Galantamine Galantamine Galantamine Placebo (n = 87) 18 mg/day (n = 88) 24 mg/day (n = 56) 36 mg/day (n = 54) 19 (21.6%) 10 (17.9%) 24 (44.4%) 8 (9.2%) ● [Commercial/academic confidential information removed] ● Six published RCTs showed that galantamine appears to confer a statistically significant benefit to participants on the ADAS-cog scale when compared with placebo, whether reducing the deterioration or leading to some improvement in their condition. The benefit varies depending on the dose of galantamine. The galantamine–placebo differences in ADAScog for 8 mg/day was 1.3 points, 16 mg/day 3.1 points, 18 mg/day 1.7 points, 16 or 24 mg/day 2.5 to 2.8 points, 24–32 mg/day 1.7–3.4 points and 36 mg/day 2.3 points. [Commercial/academic confidential information removed] In addition, 14–17% more of galantamine participants were classified as responders (improving by ≥ 4 points on the ADAS-cog) than those on placebo. ● Five published [commercial/academic confidential information removed] RCTs assessed the effect of galantamine compared with placebo on the CIBIC-plus, individually showing that higher proportions of participants receiving galantamine experience improvement in their condition compared with those on placebo (0–6.5% more participants). In contrast, a higher proportion of placebo participants tend to deteriorate (4–18% more participants). Also, a higher proportion of galantamine compared with placebo participants were considered to be responders to treatment with differences of between 4% (8 mg/day) and 17% 65
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Health Technology Assessment 2006;
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The clinical and cost-effectiveness
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Objectives: To provide an update re
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List of abbreviations .............
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AChEI acetylcholinesterase inhibito
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Epidemiology and background Alzheim
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Galantamine Five published economic
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Description of underlying health pr
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TABLE 1 Estimated prevalence of AD
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as one component of their care. A n
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The a priori methods used for syste
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Data synthesis Data were synthesise
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120 Economic analysis The model str
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124 Economic analysis TABLE 70 Key
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128 Economic analysis Probability o
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130 Economic analysis Results are s
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134 Economic analysis perspective e
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Ongoing research, with relevance to
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146 Discussion and conclusions dose
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148 Discussion and conclusions effo
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150 Discussion and conclusions Stre
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1. Clegg A, Bryant J, Nicholson T,
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placebo-controlled study of donepez
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94. Brooks E, Deal L. The effect of
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of memantine in patients with moder
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376 Health Technology Assessment Pr
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