Memantine: A New Formula for Alzheimer's Disease
In nearly 20 years, aside from cholinesterase inhibitors, memantine is the only drug approved for the treatment of Alzheimer's disease (AD). Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist that blocks pathological glutamate activity while permitting normal physiological function, thus preventing glutamate-induced excitotoxicity. Three Phase III pivotal trials demonstrated memantine's efficacy in treating moderate-to-severe AD, which led to its initial approval by the EMA in 2002 and US FDA in 2003. The recommended target dose is 10 mg twice daily. The US FDA recently approved an extended-release (ER) formulation of memantine for once-daily 28-mg dosing. Memantine ER was evaluated in a 24-week placebo-controlled trial of patients with moderate-to-severe AD, which found significant benefits for cognition, global assessment, behavior and caregiver burden, but not function. The most common adverse events were headache, dizziness, diarrhea, hypertension, anxiety and influenza. Overall, memantine in all formulations has a favorable safety/tolerability profile and is safe to use with cholinesterase inhibitors. Memantine ER has yet to be evaluated against conventionally dosed immediate-release memantine.
Alzheimer's disease (AD) is a devastating illness that affects countless people across all nations. It burdens not only the patient who is suffering with AD, but also family members and society at large. According to a review of global dementia prevalence and world population estimates by the United Nations, approximately 35.6 million people worldwide are thought to have dementia; this is expected to increase to over 115 million by the year 2050. Given that the incidence rates of both dementia in general and AD in particular are found to grow with increasing age, even beyond 90 years, and that the first group of baby boomers will turn 65 years in 2011, this expected tripling of the number of patients with AD by 2050 is expected.
The most recognizable symptom of AD involves problems with memory, however additional difficulties with cognition and executive functioning, impairment in the ability to carry out daily activities and the emergence of neuropsychiatric symptoms are also commonly experienced by patients with the disease. Evidence has demonstrated that across all age groups, mortality rates are higher in patients with dementia compared with age- and sex-matched controls without dementia. When comparing various causes of mortality in 2006, AD was found to be the seventh leading cause of death in the USA. Patients with AD have poor outcomes, poor medication compliance, higher healthcare costs and increased prevalence of comorbidities.
Worldwide, the estimated cost of dementia based on informal costs, direct costs of medical care and direct costs of social care is approximately US $422–604 billion, which is nearly 1% of the world's gross domestic product. With rising dementia prevalence, worldwide costs are projected to increase by 85% into the year 2030. Improvement in treatment options for AD and dementia is imperative.
Abstract and Introduction
Abstract
In nearly 20 years, aside from cholinesterase inhibitors, memantine is the only drug approved for the treatment of Alzheimer's disease (AD). Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist that blocks pathological glutamate activity while permitting normal physiological function, thus preventing glutamate-induced excitotoxicity. Three Phase III pivotal trials demonstrated memantine's efficacy in treating moderate-to-severe AD, which led to its initial approval by the EMA in 2002 and US FDA in 2003. The recommended target dose is 10 mg twice daily. The US FDA recently approved an extended-release (ER) formulation of memantine for once-daily 28-mg dosing. Memantine ER was evaluated in a 24-week placebo-controlled trial of patients with moderate-to-severe AD, which found significant benefits for cognition, global assessment, behavior and caregiver burden, but not function. The most common adverse events were headache, dizziness, diarrhea, hypertension, anxiety and influenza. Overall, memantine in all formulations has a favorable safety/tolerability profile and is safe to use with cholinesterase inhibitors. Memantine ER has yet to be evaluated against conventionally dosed immediate-release memantine.
Introduction
Alzheimer's disease (AD) is a devastating illness that affects countless people across all nations. It burdens not only the patient who is suffering with AD, but also family members and society at large. According to a review of global dementia prevalence and world population estimates by the United Nations, approximately 35.6 million people worldwide are thought to have dementia; this is expected to increase to over 115 million by the year 2050. Given that the incidence rates of both dementia in general and AD in particular are found to grow with increasing age, even beyond 90 years, and that the first group of baby boomers will turn 65 years in 2011, this expected tripling of the number of patients with AD by 2050 is expected.
The most recognizable symptom of AD involves problems with memory, however additional difficulties with cognition and executive functioning, impairment in the ability to carry out daily activities and the emergence of neuropsychiatric symptoms are also commonly experienced by patients with the disease. Evidence has demonstrated that across all age groups, mortality rates are higher in patients with dementia compared with age- and sex-matched controls without dementia. When comparing various causes of mortality in 2006, AD was found to be the seventh leading cause of death in the USA. Patients with AD have poor outcomes, poor medication compliance, higher healthcare costs and increased prevalence of comorbidities.
Worldwide, the estimated cost of dementia based on informal costs, direct costs of medical care and direct costs of social care is approximately US $422–604 billion, which is nearly 1% of the world's gross domestic product. With rising dementia prevalence, worldwide costs are projected to increase by 85% into the year 2030. Improvement in treatment options for AD and dementia is imperative.