Galantamine for Dementia due to Alzheimer Disease and Mild Cognitive Impairment

Is galantamine effective in treating patients with Alzheimer disease and mild cognitive impairment?

In people with mild to moderate Alzheimer disease, treatment with galantamine, 8 to 12 mg twice daily, slows the decline in cognitive function, behavioral function, and functional disability at 6 months compared with placebo.¹ Galantamine also slows the decline in global function at 6 months. However, it leads to more all-cause discontinuation of pharmacotherapy and more nausea.

For people with mild cognitive impairment, galantamine is responsible for more all-cause discontinuation of pharmacotherapy, nausea, and death compared with placebo.¹ (Strength of Recommendation: A, consistent, good quality, patient-oriented evidence.)

Approximately 6.9 million people older than 65 years in the United States are living with dementia, and this number will increase as the population ages.² Alzheimer disease is the most common form of dementia among older people. The disease progresses over time and impairs people's cognitive and behavioral functions and activities of daily living. People with mild cognitive impairment have milder symptoms than those with dementia, and they typically do not interfere with daily activities. Cholinesterase inhibitors, including donepezil (Aricept), galantamine, and rivastigmine, as well as the N-methyl-d-aspartate receptor antagonist, memantine, are thought to slow the decline of cognitive function in dementia.^3,4 No drugs are currently approved to treat mild cognitive impairment. The authors of this Cochrane review sought to assess the effectiveness of galantamine in treating the symptoms of Alzheimer disease and mild cognitive impairment.¹

This Cochrane review includes 21 double-blind, parallel-group, randomized controlled trials comparing oral galantamine with placebo.¹ Participants (n = 10,990; average age = 74 years) met criteria for mild cognitive impairment or Alzheimer disease according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria, Diagnostic and Statistical Manual of Mental Disorders, 3rd revised ed., criteria for primary degenerative dementia of the Alzheimer type, or Diagnostic and Statistical Manual of Mental Disorders, 4th ed., criteria for dementia of the Alzheimer type. Most studies included people with mild or moderate Alzheimer disease. Studies lasted from 8 weeks to 2 years, with 24 weeks being the most common duration. Cognitive function was measured with the standard and expanded Alzheimer's Disease Assessment Scale–Cognitive Subscale 11 or 13 or the Mini-Mental State Examination. Change in global function was measured with the Clinician's Interview-Based Impression of Change plus Caregiver Input Global Rating score. Activities of daily living were measured with the Alzheimer's Disease Cooperative Study–Activities of Daily Living scale. Functional disability was measured with the Disability Assessment for Dementia scale. Behavioral function was measured with the Neuropsychiatric Inventory. Dementia severity was measured with the Clinical Dementia Rating–Sum of Boxes instrument. Progression from mild cognitive impairment to dementia was defined as a change of Clinical Dementia Rating–Sum of Boxes score from 0.5 to 1.0 or higher.

For participants with dementia due to mild to moderate Alzheimer disease, use of galantamine, 8 to 12 mg twice daily, improved cognitive function (mean difference [MD] = −2.86; 95% CI, −3.29 to −2.43; six studies; n = 3,049), behavioral function (MD = −1.63; 95% CI, −3.07 to −0.2; two studies; n = 1,043), and functional disability (MD = 2.12; 95% CI, 0.75 to 3.49; three studies; n = 1,275) at 6 months compared with placebo.¹ Galantamine improved scores of global function (number needed to treat [NNT] to prevent one patient from experiencing cognitive decline over 6 months = 10; 95% CI, 8–14; moderate-certainty evidence). Participants receiving galantamine were more likely to discontinue treatment than those receiving placebo (number needed to harm [NNH] = 18; 95% CI, 11–37; high-certainty evidence), with nausea being the most common adverse reaction (NNH = 8; 95% CI, 6–10).