Neuropsychiatric symptoms in patients with AD are associated with increased patient and caregiver distress, nursing home placement, and costs of care, and they can occur in up to 98% of such patients, said presenter Alan Blau, PhD, Therapeutic Specialist, Neurology, External Affairs, Forest Research Institute, Fairfield, Connecticut.

Use of antipsychotics to treat neuropsychiatric symptoms can worsen cognitive function and with safety concerns in patients with AD. Researchers have suggested that the beneficial effects on behavioural symptoms seen with cholinesterase inhibitors and the NMDA receptor antagonist memantine might prove useful in these situations.

To analyse further the effect of memantine treatment compared with placebo in these patients, researchers conducted a post-hoc analysis to evaluate the effects on NPI seen in a previously reported 24-week study of patients with moderate to severe AD taking concomitant donepezil treatment and treated with memantine 10 mg twice daily or placebo.

The inclusion criteria for the original 24-week study were for outpatients 50 years or older with probable AD, showing a Mini-Mental State Examination (MMSE) score of 5 to 14. They also needed to have shown at least 6 months of donepezil treatment 5 or 10 mg/day at a stable dose for at least 3 months.

Baseline demographics and disposition of 201 patients randomised to placebo plus donepezil and 202 randomised memantine plus donepezil showed no significant differences between these two treatment groups.

Efficacy assessments were based initially on total NPI scores, which were then divided for the responder analysis according to 4 behavioural subscales: mood; psychosis; frontal; and other (apathy, aberrant behaviour). Positive responses within each were defined as an improvement or no change in the NPI items that constitute that subscale, which were evaluated according to observed cases (OC) and last observation carried forward (LOCF).

For the total NPI scores, significant benefits were seen for memantine over placebo as mean changes from baseline by visit (OC; P < .001) and at endpoint (LOCF; P = .002).

When analysed at week 12, the memantine treatment produced a greater rate of response than placebo for both mood (LOCF; P = .027) and psychosis (LOCF; P = .008) symptoms.

For the study endpoint (24 weeks; LOCF), memantine treatment continued to produce significantly better responses than placebo for mood and psychosis: mood (P < .01); psychosis (P < .001), with significance also seen for the "other" behavioural subscale (P = .05).

This responder analysis of individual behavioural subscales of the original NPI analysis has allowed the researchers to show that memantine can provide specific behavioural benefits for symptoms related to mood and psychosis in these patients.

The researchers stated that further studies are warranted for the use of memantine in the improvement of neuropsychiatric symptoms in patients with moderate to severe AD.

This study was supported by funding from Forest Laboratories, Inc.


[Presentation title: The Effect of Memantine on Distinct Behaviour Syndromes in Moderate to Severe Alzheimer's Disease Patients. Abstract P.5.a.010]

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