Cholinesterase memantine

Alternatively, consider memantine or cholinesterase inhibitor therapy alone. Behavioral symptoms may require additional pharmacologic approaches. 

Memantine (Namenda) blocks glutamatergic neurotransmission by antagonizing N-methyl-D-aspartate receptors, which may prevent excitotoxic reactions. It is used as monotherapy, and data suggest that when it is combined with a cholinesterase inhibitor, there is improvement in cognition and activities of daily living. 

Cholinesterase inhibitors and memantine are first-line therapy in early management of behavioral symptoms. Modest improvement may be achieved. 

Alzheimer s Disease This disease is due to the accumulation of j8-amyloid protein in the brain. The protein is believed to trigger brain degeneration through cell death of the neurons. Alzheimer s disease is characterized by loss of memory and intellectual performance, and slowness in thought. In the United States, a class of drugs called cholinesterase inhibitors is approved to treat Alzheimer s disease. Both Europe and the United States have approved a drug called memantine for treatment of Alzheimer s disease. 

The side effects of memantine are generally mild and include headache, dizziness, and constipation. Memantine is started at an initial dose of 5 mg each morning and is increased to 5 mg twice daily after 1 week. The maximum dose of memantine is 10 mg taken twice daily. A recent study indicates that memantine works syner-gistically with cholinesterase inhibitors (see Section 10.5.5), and it has quickly become routine clinical practice to coadminister memantine with one of these agents. 

The key to successful brain protection for Alzheimer s disease is the newly introduced NMDA receptor antagonist, memantine. Family members should be advised that the protection provided by memantine will slow the progression of Alzheimer s disease, but it does not halt or reverse the course of the illness. Memantine is now commonly coadministered with a cholinesterase inhibitor. 

Geriatric Considerations - Summary Memantine is modestly effective for treatment of cognitive decline associated with moderate-to-severe Alzheimer s disease. Furthermore, for persons with moderate-to-severe AlzheimeFs disease using cholinesterase inhibitors, there is some evidence that memantine confers some additional benefit. Memantine is expensive, and its cost-effectiveness has not been demonstrated. Persons using drugs to treat Alzheimer s should be monitored closely, and prescribers should have a low threshold for discontinuing these agents if no clinical benefit is observed. 

Clinicians often use each cholinesterase inhibitor in combination with memantine however, the best evidence to date for such combination treatment is the use of memantine in patients with moderate to severe Alzheimer s disease already taking donepezil (Tariot et al. 2004). 

Excitotoxic activation of glutamate transmission via NMDA receptors has been postulated to contribute to the pathophysiology of Alzheimer s disease. Memantine binds to NMDA receptor channels in a use-dependent manner and produces a noncompetitive blockade. This drug appears to be better tolerated and less toxic than the cholinesterase inhibitors. Memantine is available as Namenda in 5 and 10 mg oral tablets. 

Q8 The drugs currently licensed for Alzheimer s disease in Britain are cholinesterase inhibitors, with one exception-memantine hydrochloride. This agent... 

Alzheimer s disease) and donepezil (79). These findings support the potential for combining memantine and cholinesterase inhibitors in patients with Alzheimer s disease. 

Alisky JM. Could cholinesterase inhibitors and memantine alleviate HIV dementia J Acquir Immune Defic Syndr 2004 38 1-3. 

Altematively, arnsider memantine or cholinesterase inhibitor therapy alone. 

In contrast to cholinesterase inhibitors, which are indicated tor mild to moderate Alzheimer disease, memantine is indicated tor moderate to severe Alzheimer disease Recently approved in the U.S. but available for many years in other countries (e.g., Germany)... 

Parsons CG, Danysz W, Dekundy A, Pulte I (2013) Memantine and cholinesterase inhibitors Complementary mechanisms in the treatment of Alzheimer s disease. Neurotox Res 24 358-369... 

Zhu CW, Livote EE, Scarmeas N, Albert M, Brandt J, Blacker D et al (2013) Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer s disease. Alzheimers Dement 9 733-740... 

Combination Treatment of Cholinesterase Inhibitors with Memantine. . 44... 

Recent studies have reported that galantamine also improves the cognitive performance of patients with autism (Nicolson et al., 2006) and, unlike other cholinesterase inhibitors, decreases the negative symptoms in patients with schizophrenia (Schubert et al., 2006). Eor more severe Alzheimer s disease, memantine, an antagonist of N-methyl-D-aspartate (NMDA) receptors, has also been approved. A number of newer drugs undergoing clinical trials for Alzheimer s disease work by a variety of other mechanisms, although a common theme appears to be neuroprotection (Robertson and Mucke, 2006). 

Cholinesterase inhibitors and memantine are used to treat cognitive symptoms of AD other medications have been suggested to be beneficial because of their potential preventive or cognitive effects. 

Overall, memantine has been well tolerated in clinical trials. The most frequent adverse events associated with memantine include constipation, confusion, dizziness, headache, coughing, and hypertension. As some of these side effects are also reported with cholinesterase inhibitors, caution should be used when administering memantine with this class of medications. ... 

Memantine is likely to be used as monotherapy and also in combination with cholinesterase inhibitors, particularly in patients with moderate to severe AD. Memantine should be initiated at 5 mg once a day and increased weekly by 5 mg a day to the effective dose of 10 mg twice daily. It may be given with or without food. Dosing of 10 mg daily is recommended in patients with creatinine clearance of 40 to 60 mL/min and patients with severe renal impairment (creatinine clearance <40 mL/min) should not receive memantine. ... 

Because the effects of cholinesterase inhibitors are modest, there is great interest in developing alternative or additional treatments for AD. Most of these alternatives have shown promise in epidemiologic studies however, benefit in prospective clinical trials has been limited or insufficiently stndied. Memantine is the first non-cholinesterase inhibitor approved for AD treatment. Its role in treatment will become more clearly defined in the next several years. 

Studies with agents other than cholinesterase inhibitors are rare but should increase in number as the understanding of AD and its potential treatments improve. A 28-week placebo-controlled trial with memantine reported cost savings and a lower incidence of institutionalization than in the placebo group. Caregiver costs decreased by 824/month and societal costs by 1090/month with memantine therapy. However, direct medical costs to the patient treated with memantine were higher than placebo due to cost of the medication. 

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