THERAPEUTICS

Brands

• Namenda, Namenda XR, Ebixa, Namzaric (memantine + donepezil)

Generic?

• Yes (except XR)

Class

• NMDA receptor antagonist

Commonly Prescribed for

(FDA approved in bold)

• Alzheimer's dementia (AD) (moderate or severe)

• Parkinson's disease-related dementia

• Dementia with Lewy bodies (DLB)

• Vascular dementia

• HIV dementia

• Migraine prophylaxis

• Attention deficit hyperactivity disorder

• Binge-eating disorder

How the Drug Works

• An uncompetitive NMDA receptor antagonist that prevents the tonic pathological influx of Ca2+ (caused by amyloid-β binding on NMDA receptors) but permits the transient strong physiological glutamatergic signal

• It also reduces oxidative stress in postsynaptic neurons and targets extracellular NR2B subunits (“death” receptors), which may be related to the pathological process of AD

• It is also a 5-HT3 antagonist of similar potency

• Although symptoms of AD can improve, memantine does not prevent disease progression

How Long Until It Works

• Weeks to months

If It Works

• Continue to use but symptoms of dementia usually continue to worsen

If It Doesn't Work

• Non-pharmacological measures are the basis of dementia treatment. Maintain regular schedules and routines. Avoid prolonged travel, unnecessary medical procedures or emergency room visits, crowds, and large social gatherings

• Limit drugs with sedative properties such as opioids, hypnotics, AEDs, and TCAs

• Treat other underlying disorders that can worsen symptoms, such as hyperglycemia or urinary difficulties

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Addition of cholinesterase inhibitors may be beneficial. In one study donepezil plus memantine reduced the rate of progression compared to that in those taking donepezil alone

• Treat depression or apathy with SSRIs but be cautious for increased risk of AEs (e.g., QTc prolongation, injurious falls). Avoid TCAs in demented patients due to risk of confusion. In dementia patients with severe depression, electroconvulsive therapy can be an option

• For significant confusion and agitation avoid neuroleptics (especially in DLB) because of the risk of neuroleptic malignant syndrome. Atypical antipsychotics (e.g., risperidone, clozapine, aripiprazole) or SSRIs can be used instead