Memantine relieved Lewy body dementia symptoms

by Heidi Splete

Memantine might improve behavioral symptoms and reduce brain deterioration in patients with mild to moderate Lewy body dementia, but not Parkinson's disease dementia, based on data from a randomized, placebo-controlled trial.

The higher amount of Alzheimer's disease-like amyloid pathology that is normally observed in patients with dementia with Lewy bodies (DLB) might explain why the drug appears to provide symptomatic relief to that group but not to patients with Parkinson's disease dementia (PDD), in whom amyloid pathology is encountered less often, Dr. Murat Emre of Istanbul (Turkey) University and his colleagues reported.

Dr. Emre and his coauthors studied memantine, which is approved in the United States for treatment of moderate to severe Alzheimer's disease, because previous studies had suggested that the drug might yield similar benefits in Lewy body-related dementias such as PDD or DLB.

The researchers randomized 78 patients with DLB and 121 patients with PDD to a 20-mg dose of memantine once daily or a placebo. Concomitant use of cholinesterase inhibitors was not allowed (Lancet Neurology 2010 Aug. 23 [doi:10.1016/S1474-4422(10)70194-0]).

Patients were assessed at screening, at baseline, and at weeks 4, 12, 16, and 24. The study included patients from 30 sites in eight countries. The average age of the patients was 74 years, and almost 100% were white.

In DLB patients, memantine significantly improved scores on the ADCSCGIC (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change) scale from baseline to 24 weeks, compared with placebo (mean change from baseline, 3.3 vs. 3.9, respectively). In addition, NPI (Neuropsychiatry Inventory) scores improved significantly more from baseline to 24 weeks in memantine-treated patients than in placebo-treated patients (mean change from baseline, -4.3 vs. 1.7, respectively).

Among PDD patients, memantine did not significantly change scores with either measurement, compared with placebo.

"Memantine might exert stronger beneficial effects in patients with more prominent Alzheimer's disease-type pathology," the investigators wrote. The differences in effects between DLB and PDD patients also could be accounted for by the range in symptoms and in concomitant drug use between these two groups, they added.

The most commonly reported adverse events were falls and sleepiness, which were reported by no more than 10% of the patients in each group. A total of 11 patients (5 with DLB and 6 with PDD) in the memantine group and 12 patients in the placebo group (7 with DLB and 5 with PDD) withdrew from the study because of adverse events, which included two cases of stroke in the memantine group and two cases each of agitation, confusion, and tremor in the placebo group.

Complete study data were available on 159 patients. The efficacy analysis included 97 patients in the memantine group and 93 patients in the placebo group.

The study was limited in part by its size, but the low incidence of adverse events and improvements among DLB patients support the use of memantine as an option, the researchers said.

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Major Finding: NPI scores improved significantly more from baseline to 24 weeks in memantine-treated patients than in placebo-treated patients (mean change from baseline, -4.3 vs. 1.7, respectively).

Data Source: A multicenter, randomized, double-blind, placebo-controlled trial of 199 patients.

Disclosures: The study was funded by Lundbeck, a manufacturer and distributor of memantine. Dr. Emre and some of his coauthors disclosed financial relationships with Lundbeck and other pharmaceutical companies. One author is an employee of Lundbeck.

BY HEIDI SPLETE

FROM THE LANCET NEUROLOGY

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New Addition to Management Plan?

Definitive treatments for Lewy body dementias are lacking. But the findings from the study by Dr. Emre and colleagues show that memantine significantly improved global status scores in patients with Lewy body dementia in particular.

Patients with Lewy body dementia or related dementias present complex clinical management challenges, and the high rate of psychopathological symptoms and baseline antidepressant use in the study population could be cause for concern. But the study also raises the possibility that memantine could improve global function and cognition by improving mood symptoms.

Overall, the study results suggest that memantine might be useful for symptom relief in patients with Lewy body dementia. More research is needed, but memantine could be part of a plan to manage DLB and PDD symptoms until definitive cognitive therapies are developed.

LAURA MARSH, M.D., is from Baylor College of Medicine and the Michael E. DeBakey Veterans' Affairs Medical Center, both in Houston. Her comments are paraphrased from an editorial (Lancet Neurology 2010 Aug, 23 [doi:10.1016/S1474-4422(10)70208-8]). Dr. Marsh has received funding from Forest Research Institute to study the effects of memantine on the treatment of dementia in Parkinson's disease.