EPA-1267 – Dose-dependent Tolerance of Memantine Treatment in Patients with Dementia: Insights from Clinical Trials and an Observational Study

Abstract

Introduction:

Memantine has been registered worldwide for the treatment of moderate to severe dementia of Alzheimer's type (AD). However, both historical experiences and contemporary research showed its possible utility also in other types of dementia, including that of vascular origin (VaD) and Lewy body pathology-related (DLB/PDD). Maximum labelled dosing of memantine for patients with AD and the same was used in studies with VaD and PDD/DLB. Memantine seem to be well tolerated in AD patients, less is known considering other dementias.

Method:

Naturalistic observation of the group of 120 AD, 65 VaD and 30 DLB/PDD patients from the memantine initiation with a maximum one year observation period. Drop-out or dose reduction due to adverse effects where analyzed.

Results:

Considerably lower fraction of patients with other that AD diagnoses achieved maximum dose of 20 mg/day and needed dose-reduction due to adversity. Moreover, numerically more patients with DLB/PDD than both VaD and AD did not tolerate any dose of memantine; this difference, however, due to small numbers did not reach statistical significance. The most common symptoms which resulted in dose-reduction or drug discontinuation included agitation, excessive sedation and gastrointestinal complications.

Conclusion:

Similarly to previously known observations with cholinesterase inhibitors, patients with dementia due to AD tolerated memantine better than those with other dementias. The phenomenon underlying mechanism is currently unknown. Nevertheless, despite obscure nature, it may have important pragmatic consequences and may lead clinicians to both greater vigilance and possibly targeting at lower memantine doses in patients with dementias other than AD.