Optimal dosing of galantamine in patients with mild or moderate Alzheimer's disease: post Hoc analysis of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Galantamine (hydrobromide), a reversible acetylcholinesterase inhibitor and allosteric nicotinic receptor modulator, slows cognitive and functional decline in mild to moderate dementia of the Alzheimer's type. Although several drugs are indicated for mild to moderate Alzheimer's disease (AD), no published study has separately analysed mild and moderate AD subgroups to assess the effect of dosage.

OBJECTIVE: To compare the efficacy and safety of galantamine 16 and 24 mg/day in patient subgroups with mild or moderate AD.

METHODS: This post hoc analysis (n = 838) of a 5-month, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of galantamine 16 and 24 mg/day in a subgroup of patients with mild AD (Mini-Mental State Examination [MMSE] >18) and a subgroup with moderate AD (MMSE 10-18). Efficacy outcomes included the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score and treatment response (ADAS-cog maintenance [>or=0-point improvement], improvement >or=4 points and improvement >or=7 points).

RESULTS: Mean ADAS-cog scores of patients with mild AD demonstrated significant improvement from baseline with galantamine 16 and 24 mg/day (p < 0.001 for both), whereas cognitive function did not change significantly for placebo recipients (p = 0.559). Patients with moderate AD improved with galantamine 24 mg/day (p = 0.009) but not with 16 mg/day (p = 0.768); a decline occurred with placebo (p < 0.001). A greater proportion of patients treated with galantamine 16 mg/day (76% and 52% for mild and moderate AD, respectively) or 24 mg/day (69% and 61%, respectively) demonstrated a treatment response (i.e. ADAS-cog was maintained or improved) relative to placebo (55% and 28%, respectively; p < 0.05). Patients with moderate AD trended toward greater response with the 24 mg/day dosage than with the 16 mg/day dosage. Galantamine was well tolerated. Adverse events were comparable for all study groups with mild or moderate AD.

CONCLUSION: This post hoc analysis suggests that galantamine 16 mg/day is the optimal dosage for patients with mild AD, as similar efficacy is observed with the 24 mg/day dose. However, patients with moderate AD appear to gain additional benefit from galantamine 24 mg/day.