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Evidence summaries

Galantamine for Alzheimer's Disease

Galantamine appears to be effective for slightly improving cognitive function at doses of 16 mg/day or greater, in people with mild to moderate Alzheimer's disease. Level of evidence: "B"

The quality of evidence is downgraded by indirectness of evidence (short follow-up, surrogate outcomes).

A treatment attempt with galantamine is recommended for improving cognitive function in Alzheimer's disease as an alternative to other cholinesterase inhibitors.

The recommendation is strong because of possible positive effect on cognitive function. The cost of galantamine is low.

A Cochrane review [Abstract] 1 included 10 studies with a total of 6805 subjects. Treatment with galantamine led to a significantly greater proportion of subjects with improved or unchanged global rating scale rating (8 studies) at all dosing levels except for 8 mg/d, and to significantly greater reduction in ADAS-cog score at all dosing levels (n=8), with greater effect over six months compared to three months. Confidence intervals for the ORs overlapped across the dose range of 16 mg to 36 mg per day. For example, treatment effect for 24 mg/d over six months was 3.1 point reduction in ADAS-cog (95% CI 2.6-3.7; 4 trials, ITT). Galantamine's adverse effects appeared similar to those of other cholinesterase inhibitors and to be dose related. Prolong release / once daily formulation of galantamine at 16-24 mg/d had similar efficacy and side-effect profile as the equivalent twice-daily regime.

A NICE systematic review [PubMed] 2 included 6 published and 1 unpublished RCT studying galantamine in doses of 8−36 mg/day. The duration of the studies varied from 3 months (n = 3) and 5 months (n = 1) to 6 months (n = 2). Altogether there were 3 324 patients with mild to moderate Alzheimer's disease (1 051 in placebo and 2 273 in galantamine group), with a mean age between 70 and 80 years.

  • All six found astatistically significant difference with the groupreceiving galantamine (16-32 mg/day) experiencingan improvement compared to a deterioration forthe placebo group. The benefits of treatment with galantaminecompared with placebo on the ADAS-cog scalewere shown through meta-analyses for different dosesand lengths of study. The fixed-effect model for24 mg/day galantamine compared with placebo(981 patients) showed a weighted mean difference on ADAS-cogfavouring galantamine at 3 months [WMD -3.00(95% CI: -5.23 to -0.77)] and 6 months follow-up[WMD -3.28 (95% CI: -3.89 to -2.67)]. Similarly, the fixed-effect models for24-32 mg/day compared with placebo [WMD-1.65 (95% CI: -2.43 to -0.87)] and for 32 mg/daygalantamine compared with placebo [WMD -3.29(95% CI: -4.14 to -2.45)] favoured galantamine at6 months follow-up.

A systematic review [PubMed] 3 included 23 studies of which 4 assessed galantamine (n = 2265). Cognitive effects were significant at 24 weeks measured by the ADAS-cog using galantamine 24 mg/day (-3.03, 95% CI -3.66 to -2.41) and galantamine 32 mg/day (-3.2, 95% CI-3,28 to -3,12). No behavioral benefits were observed.

Clinical comments

Although the clinical benefits in the included studies were small, a treatment attempt is warranted due to the debilitating nature of the disease and its impact on the patient's quality of life.

References

  • Loy C, Schneider L. Galantamine for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev 2006 Jan 25;(1):CD001747. [PubMed]
  • 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;10(1):iii-iv, ix-xi, 1-160. [PubMed]
  • Tan CC, Yu JT, Wang HF et al. Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis 2014;41(2):615-31. [PubMed]

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