Memantine (Namenda) is Not Recommended for Frontotemporal (Frontal Lobe) Dementia
Do not use memantine for frontotemporal dementia—the highest quality randomized controlled trial demonstrates no benefit on neuropsychiatric symptoms or global function, and it is not FDA-approved for this indication. 1
Evidence Against Use in Frontotemporal Dementia
The definitive evidence comes from a rigorous multicentre, randomized, double-blind, placebo-controlled trial that specifically evaluated memantine in frontotemporal lobar degeneration (FTD):
No benefit on primary outcomes: Memantine 20 mg daily for 26 weeks showed no effect on neuropsychiatric symptoms (NPI score difference 2.2 points, 95% CI -3.9 to 8.3, p=0.47) or clinical global impression of change (CGIC difference 0.0,95% CI -0.4 to 0.4, p=0.90) 1
Increased cognitive adverse events: Patients taking memantine experienced more frequent cognitive adverse events (6 patients) compared to placebo (1 patient), suggesting potential harm 1
Study quality: This trial enrolled 81 patients with behavioral variant FTD or semantic dementia confirmed by characteristic brain atrophy, making it the most robust evidence available 1
Contradictory Lower-Quality Evidence
One open-label, self-controlled trial (without placebo control) suggested possible benefit in moderate-to-severe bvFTD for agitation, depression, apathy and disinhibition, but this study design is inherently prone to bias and cannot override the negative randomized controlled trial 2. The lack of blinding and placebo control makes these findings unreliable for clinical decision-making.
FDA-Approved Indications
Memantine is FDA-approved only for moderate-to-severe Alzheimer's disease, not for frontotemporal dementia 3. The evidence supporting its use is specific to:
Moderate-to-severe Alzheimer's disease: High-certainty evidence shows small but consistent clinical benefits in cognition (3.11 SIB points), global function (0.21 CIBIC+ points), activities of daily living (1.09 ADL19 points), and behavior (1.84 NPI points) 4
Vascular dementia: Moderate-certainty evidence shows probable small benefit for cognition (2.15 ADAS-Cog points) and behavior (0.47 NOSGER points) 5, 4
Clinical Bottom Line
Avoid prescribing memantine for frontotemporal dementia. The pathophysiology of FTD differs fundamentally from Alzheimer's disease—FTD involves primarily tau or TDP-43 protein pathology affecting frontal and temporal lobes, while memantine's mechanism (NMDA receptor antagonism targeting glutamate excitotoxicity) is designed for the amyloid and tau pathology of Alzheimer's disease 1, 6. The randomized controlled trial data definitively show no benefit and potential for increased cognitive adverse events in this population 1.
If behavioral symptoms require treatment in FTD, consider alternative evidence-based approaches such as SSRIs for specific behavioral symptoms, rather than memantine 5.