Memantine for Alzheimer's Disease

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

A treatment attempt with memantine is recommended for patients with moderate to severe but not mild Alzheimer's disease as an alternative to cholinesterase inhibitors or combined with them.

The recommendation is strong because of possible positive effect on cognitive function, activities of daily living and behavior and mood. Memantine is well-tolerated in moderate to severe Alzheimer's disease and the cost is low.

A Cochrane review [Abstract] 1 included 29 studies with a total of 7885 subjects with Alzheimer's disease.

• Moderate to severe Alzheimer's disease. High-certainty evidence from up to 14 studies in around 3700 participants consistently shows a small clinical benefit for memantine versus placebo. Clinical global rating: 0.21 CIBIC+ points (95% confidence interval (CI) 0.14 to 0.30); cognitive function: 3.11 Severe Impairment Battery (SIB) points (95% CI 2.42 to 3.92); activities of daily living: 1.09 ADL19 points (95% CI 0.62 to 1.64); and behaviour and mood: 1.84 Neuropsychiatric Inventory (NPI) points (95% CI 1.05 to 2.76). Risk ratio (RR) of people discontinuing memantine compared to placebo is 0.93 (95% CI 0.83 to 1.04) corresponding to 13 fewer people per 1000 (95% CI 31 fewer to 7 more).
• Mild Alzheimer's disease (MMSE 20 to 23 points). Mainly moderate-certainty evidence based on post-hoc subgroups from up to four studies in around 600 participants suggests there is probably no difference between memantine and placebo. In this subgroup, memantine may increase the numbers of people discontinuing treatment because of adverse events (RR 2.12, 95% CI 1.03 to 4.39) compared to placebo.

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.

Memantine is a suitable option for patients who experience bradycardia or syncope.

Combination therapy with cholinesterase inhibitors and memantine appears to be beneficial for the treatment of moderate to severe Alzheimer's disease in terms of behavioral disturbances and activities of daily living Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer's Disease.

References

• McShane R, Westby MJ, Roberts E et al. Memantine for dementia. Cochrane Database Syst Rev 2019;(3):CD003154. [PubMed]