Out Of The Pipeline

Memantine: New option for advanced Alzheimer’s

Current Psychiatry. 2004 January;3(1):64-77

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In a third pivotal trial, 403 patients with AD were randomly assigned to memantine, 20 mg/d, or placebo across 24 weeks. All patients were also taking the cholinesterase inhibitor donepezil, 10 mg/d.⁹ The memantine/donepezil group scored higher than the placebo/donepezil group on several scales. MMSE scores at entry ranged from 5 to 14. Drug-placebo differences were similar in magnitude to those observed in earlier studies.

TOLERABILITY

Controlled trials of memantine in patients with AD demonstrated few adverse effects.

Reisberg et al⁸ reported that 84% of memantine-group patients and 87% of the placebo group experienced adverse effects. More placebo-group than memantine-group patients (17% vs. 10%) discontinued the study because of adverse events. Agitation was the most commonly cited reason for discontinuation (7% of the placebo group and 5% of those taking memantine). No adverse event was significantly more common in the memantine group.

Tariot et al⁹ noted that confusion and headache were somewhat more common among those receiving memantine versus placebo. In other studies, symptoms possibly related to memantine included headache, akathisia, insomnia, increased motor activity, and excitement.^6,10-12

CO-ADMINISTRATION WITH CHOLINESTERASE INHIBITORS

The range of AD severity targeted by memantine overlaps that addressed by the cholinesterase inhibitors donepezil, galantamine, and rivastigmine, which are indicated for mild to moderate AD. Many patients will receive both memantine and a cholinesterase inhibitor.

Data show this combination therapy to be clinically safe. Tariot et al⁹ found no increase in adverse events when memantine was co-administered with donepezil. Post-marketing surveillance studies in Germany indicate low rates of adverse events among patients receiving a cholinesterase inhibitor and memantine.¹³ In-vitro laboratory data indicate that memantine does not affect or interact with cholinesterase inhibition.¹⁴

Memantine is not metabolized by liver enzymes. No interaction with antidepressants or antipsychotics commonly used in AD is anticipated.

CLINICAL IMPLICATIONS

Memantine, with a mechanism of action different from that of existing agents, offers a new avenue of therapeutic intervention and expands the spectrum of patients who may benefit from FDA-approved drug therapy.

Research is needed to determine whether memantine is useful in earlier stages of AD and in treating mild cognitive impairment. The role of glutamate excitotoxicity in AD also needs to be defined.

Related resources

Alzheimer’s Association. www.alz.org
Mendez M, Cummings JL. Dementia: a clinical approach(3rd ed). Boston: Butterworth Heinemann, 2003.

Drug brand names

Amantadine • Symmetrel
Cimetidine • Tagamet
Dantrolene • Dantrium
Donepezil • Aricept
Galantamine • Reminyl
Memantine • Namenda
Procainamide • Procanbid
Procainamide • Exelon

Disclosure

The author has received research/grant support and/or is a consultant to AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eisai Pharmaceuticals, Eli Lilly and Co., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., and Pfizer Inc.

Treating late-life decline: When more is less

Memantine: New option for advanced Alzheimer’s

References

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