Memantine for dementia
Memantine is beneficial for people with moderate to severe Alzheimer's disease. Memantine has a beneficial effect on central nervous system activity and is a potential treatment for Alzheimer's disease, and for vascular and mixed dementia. The results to date suggest a beneficial effect on cognitive function and functional decline in patients with moderately to severe Alzheimer's disease, and on cognitive function in vascular dementia. These effects are supported by a significant improvement in the clinical impression of change. The adverse effects profile and tolerability are good; there were low and similar rate of drop-outs from treatment and placebo groups in all of the studies. Agitation is less common with memantine. Memantine is a promising drug for the treatment of moderate to severe Alzheimer's disease. The effect of memantine in mild to moderate AD is unknown.
Available from: Andrew Whyment
- "The drug is thought to act by blocking the NMDA receptor channel (Lipton, 2004), and this allows for voltage dependent inhibition of Ca 2þ influx (Danysz and Parsons, 2003; Parsons et al., 1999). In moderate to severe cases of AD, memantine has been shown to be of relatively limited, albeit clinically relevant benefit in slowing behavioral deterioration (Areosa et al., 2005; Reisberg et al., 2003; Tariot et al., 2004). Furthermore, in mild to moderate cases of AD, memantine has recently been reported to be of no clinical benefit (Schneider et al., 2011). "
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ABSTRACT: Oligomers of beta-amyloid (Aβ) are implicated in the early memory impairment seen in Alzheimer's disease before to the onset of discernable neurodegeneration. Here, the capacity of a novel orally bioavailable, central nervous system-penetrating small molecule 5-aryloxypyrimidine, SEN1500, to prevent cell-derived (7PA2 [conditioned medium] CM) Aβ-induced deficits in synaptic plasticity and learned behavior was assessed. Biochemically, SEN1500 bound to Aβ monomer and oligomers, produced a reduction in thioflavin-T fluorescence, and protected a neuronal cell line and primary cortical neurons exposed to synthetic soluble oligomeric Aβ(1-42). Electrophysiologically, SEN1500 alleviated the in vitro depression of long-term potentiation induced by both synthetic Aβ(1-42) and 7PA2 CM, and alleviated the in vivo depression of long-term potentiation induced by 7PA2 CM, after systemic administration. Behaviorally, oral administration of SEN1500 significantly reduced memory-related deficits in operant responding induced after intracerebroventricular injection of 7PA2 CM. SEN1500 reduced cytotoxicity, acute synaptotoxicity, and behavioral deterioration after in vitro and in vivo exposure to synthetic Aβ and 7PA2 CM, and shows promise for development as a clinically viable disease-modifying Alzheimer's disease treatment.
Available from: bap.org.uk
- "There have been no new data for memantine since the last guideline. The effects of memantine in VaD have been reviewed by Bocti et al. (2007), Kavirajan and Schneider (2007), McShane et al. (2006) and Thomas and Grossberg (2009) (See Table 5 for recommendations). Frontotemporal and other dementias FTD comprises a group of clinical syndromes associated with circumscribed degeneration of the prefrontal and anterior temporal lobes. "
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ABSTRACT: The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.
Available from: Edmund Juszczak
- "Although there is evidence that these drugs are effective in the mild to moderate range of severity, there is at present little evidence to guide clinicians at the critical decision point when patients deteriorate beyond moderate to severe dementia. Memantine has systematic review level evidence to support efficacy in late stage AD  and has been widely prescribed at this stage. Again, however, there is not an adequate evidence base to guide decisions about patients compliant with a cholinesterase inhibitor but who have reached the moderate to severe point where they might be considered for memantine treatment. "
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ABSTRACT: Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.
DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline, 6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone interview to record institutionalization.
There is considerable debate about the clinical and cost effectiveness of anti-dementia drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those managing patients at a particularly important clinical transition point.
Current controlled trials ISRCTN49545035.
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