Two galantamine titration regimens in patients switched from donepezil

In addition to inhibiting acetylcholinesterase, galantamine has allosteric-modulating activity at nicotinic receptors. This may make galantamine an attractive option for patients starting treatment for Alzheimer's disease (AD), but also for those who have not benefited from their current therapy. This study explored outcomes in subjects with AD transitioning from donepezil because of insufficient tolerability or efficacy.

Subjects previously receiving donepezil for mild-to-moderate AD were enrolled in a 12-week randomized, open-label study. After screening and a 7-day washout, subjects were randomly allocated to galantamine fast (8 mg/week increments) or slow (8 mg/4 week) titration to 16-24 mg. Efficacy outcomes included the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog/11), Mini-Mental State Examination (MMSE), Clinician's Interview-Based Impression of Change - Plus Caregiver's Input (CIBIC-plus) and Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL).

Eighty-six of 89 patients (fast titration, n = 44; slow titration, n = 45) completed the study. At week 12, ADAS-cog/11 score improved from screening by 2.6 and 0.6 in the fast- and slow-titration arms, respectively (overall, -1.6; P = 0.002). MMSE scores improved slightly in both arms (overall, +0.9; P = 0.002). Two-thirds of patients had improvement or no change on the CIBIC-plus at week 12. ADCS-ADL scores did not change significantly from screening in either treatment arm. Galantamine was generally well tolerated; nausea (5.6%) and bradycardia (4.5%) were the most commonly reported adverse events.

Patients in whom donepezil is ineffective or poorly tolerated may benefit from a switch to galantamine.