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Behavior Problems in Moderate to Severe Alzheimer's Disease Improved With Combined Memantine and Donepezil: Presented at ANA

By Paula Moyer

CHICAGO, IL -- October 10, 2006 -- Patients with moderate to severe Alzheimer's disease who are receiving a stable dose of donepezil (Aricept) have reduced behavioral symptoms when their regimen is supplemented with memantine (Namenda), according to findings presented here at the American Neurological Association (ANA) 131^st annual meeting.

Patients receiving the adjunctive memantine performed significantly better on mood and psychosis subscales of the Neuropsychiatric Inventory (NPI), said Pierre N. Tariot, MD, director, Memory Disorders Center, Banner Alzheimers Disease Institute, Phoenix, Arizona. "This response suggests potential for memantine to provide specific benefits for behavioral symptoms."

In a presentation on October 8^th, Dr. Tariot said the study was conducted to assess the effects of memantine on behavioral symptoms that are commonly associated with Alzheimer's disease. They conducted a post hoc analysis of behavioral outcomes in a study of 403 patients with moderate to severe Alzheimer's disease.

Patients had been diagnosed with probable Alzheimer's disease and had Mini Mental Status Examination (MMSE) scores of 5 to 14. All patients had been receiving donepezil for at least 3 months prior to randomization at doses of either 5 or 10 mg daily. They were then randomized to receive either memantine at a dose of 10 mg twice daily or placebo for 24 weeks.

Individual items of the NPI were aggregated into 4 subscales: 1) mood, which pertained to depression, anxiety, irritability, nocturnal exacerbations, and changes in eating habits; 2) psychosis; which encompassed delusions, hallucinations, and agitation or aggression; 3) frontal symptoms, which consisted of euphoria or elation and disinhibition, and 4) other common Alzheimer's disease symptoms, which consisted of apathy and aberrant motor behavior.

The 2 treatment groups had similar baseline characteristics. However, at week 24, the total NPI score was significantly lower for the memantine group than the placebo group. The placebo group had an increase, or worsening, of NPI scores, while the memantine-treated patients had a slight decrease (P < .01). Therefore, there were fewer behavioral disturbances and psychiatric symptoms in memantine-treated patients.

On the mood subscale, patients on combination therapy had an average improvement of 0.4 points at the end of the study, and those on monotherapy worsened by an average of 1.6 points.

Although both groups had some worsening of symptoms on the psychosis subscale, the increase was lessened in the patients on combination therapy compared with monotherapy (P = .008). Frontal symptoms were unchanged, and the slight worsening on the other symptoms were similar between the 2 groups, an average of 0.6 for the monotherapy patients and 0.1 for those on the combination therapy.

The investigators concluded that 6 months of treatment with memantine in combination with donepezil reduced behavioral symptoms of patients with moderate to severe AD, particularly symptoms associated with mood and psychosis.

Namenda is manufactured by Forest Laboratories, Inc., which sponsored the study.


[Presentation title: NPI Subscale Analysis of Memantine/Donepezil Treatment in Moderate-to-Severe AD. Abstract S-19]

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