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Phase II data show potential benefit of memantine for patients with PD dementia, dementia with Lewy bodies

Wednesday, June 24 2009 | Comments

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What's This? Patients with Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB) seem to benefit from treatment with memantine hydrochloride, according to findings from a Phase II trial conducted in Norway, Sweden, and the United Kingdom.

Researchers randomized 72 patients with mild to moderate PDD or DLB to receive memantine (n=34; maintenance dose, 20 mg/day) or placebo (n=38) for 24 weeks. The primary outcome measure was the Clinical Global Impression of Change (CGIC) score at week 24, with possible scores ranging from 1 (substantial improvement) to 7 (substantial worsening). An improvement of 0.6 point on the CGIC was considered to be clinically significant.

In the intent-to-treat analysis, the mean CGIC score at week 24 was 3.5 in the memantine group (median, 3.0) and 4.2 in the placebo group (median, 4.0), yielding a difference of 0.7 (95% CI, 0.04-1.39; P=.03) and indicating a medium-sized effect (effect size, 0.52). This difference, the investigators noted, compares favorably with results reported in previous trials of cholinesterase inhibitors for Alzheimer's disease (AD) and PDD. At week 12, the mean difference in CGIC score was 0.59 (95% CI, 0.01-1.18; P=.02).

When the participants with PDD were evaluated separately from those with DLB, the results suggested a more pronounced global response in the patients with PDD than in those with DLB.

Secondary outcome measures included week 24 scores on the Mini-Mental State Examination (MMSE), A Quick Test of Cognitive Speed (AQT), the Neuropsychiatric Inventory, and the Disability Assessment for Dementia (DAD), and modified United Parkinson's Disease Rating Scale motor scores. The only significant between-group difference observed was in one of the AQT scores, which suggested improved speed during attentional tasks with memantine.

However, additional analysis of secondary outcome measures showed significant improvement from baseline in MMSE scores among the memantine-treated patients (mean change, 1.4 points; P=.02), compared with a nonsignificant decrease in the placebo group (mean change, 0.5 point). The between-group difference (1.9 points) was larger than that reported in key trials of cholinesterase inhibitors for AD and PDD, the authors noted, although it was not statistically significant (P=.09).

Also, DAD scores worsened significantly in the placebo group (mean change, 2.5 points; P=.004), compared with a nonsignificant decrease in the memantine group (mean change, 1.0 point).

Thirty-five patients reported incident adverse events during the trial, including 20 participants in the placebo group and 15 in the memantine group. Sixteen participants (22%) withdrew from the trial because of adverse events (memantine, n=7; placebo, n=9). All patients who withdrew did so because of adverse events, including 7 placebo-treated participants and 4 memantine-treated participants who withdrew because of worsening of the disease. Five withdrawals were deemed unrelated to PDD or DLB.

"Our current findings are encouraging and indicate the need for large multicenter studies," the researchers concluded. (Aarsland D, et al. Lancet Neurol 2009;8:613-618.)

This study was funded in part by H. Lundbeck A/S.

This information concerns a use that has not been approved by the Food and Drug Administration.

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