Page 27 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

No tacrine trial specifically reported the effect of drug treatment on caregiver burden, institutionalization,
or death.

Memantine vs. placebo

Two fair-rated RCTs 59, 60 comparing memantine to placebo met the inclusion criteria for our review.
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Although we identified one good-rated systematic review, it included only one of the two RCTs that met
our inclusion criteria so we do not discuss it further.

Both placebo-controlled trials randomized moderate to severe AD patients to memantine 20mg/day or
placebo. 59, 60 One trial required patients to be receiving stable treatment with donepezil prior to
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randomization, and thus cannot be directly compared to the trial that did not allow concomitant use of
donepezil. Population demographics were similar across trials. Outcome measures consistently used in
both trials included the CIBIC-plus, SIB, ADCS-ADL, and NPI. In both trials, memantine-treated

patients did significantly better on the SIB and ADCS-ADL than placebo-treated patients (the primary
outcome measures in both trials). However, only patients randomized to both memantine and donepezil
faired significantly better on the CIBIC-plus and NPI than patients randomized to placebo plus
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donepezil. In the memantine monotherapy study, no differences in MMSE, CIBIC-plus, GDS, or NPI
were reported between memantine- and placebo-treated patients.

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Both included trials assessed caregiver burden. 59, 60 One trial incorporated a resource utilization scale,
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and the other trial used a behavioral rating scale (BGP) that assesses caregiver dependence. Both trials
showed significantly greater improvement in caregiver burden (P < 0.01) for memantine compared to
placebo.

F. Summary of the evidence

Comparative evidence for drugs used to treat AD is limited to three open-label head-to-head efficacy
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trials; two trials compared donepezil to galantamine 27, 28 and one compared donepezil to rivastigmine.
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Evidence for the comparison of donepezil with galantamine is mixed. In one 52-week trial, donepezil
and galantamine did not differ in stabilizing symptoms or improving behavior and functional status. In a

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shorter trial (12 weeks), donepezil was superior to galantamine in its effects on cognition, functional
status, and caregiver and clinician satisfaction. The comparison of donepezil to rivastigmine is limited to
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a single 12-week trial; it produced similar improvement in cognitive scores for both drugs, although
clinician and caregiver satisfaction ratings were significantly better for donepezil. Because of limitations

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