Study results published in the current issue ofThe Lancet (vol 356, issue 9248) show that Exelon® (rivastigmine) alleviates behavioral disturbances in patients with dementia with Lewy bodies (DLB). DLB (also referred to as the Lewy body variant of Alzheimer's disease) is the second most common form of dementia1 and is characterized by severe behavioral disturbances.
"The study results show that the behavioral and cognitive symptoms in patients with dementia with Lewy bodies can be effectively treated with Exelon," said the study's lead investigator Ian McKeith, MD, FRCPsych, Professor of Old Age Psychiatry at the Institute for the Health of the Elderly, Newcastle General Hospital, University of Newcastle upon Tyne, England.
Clinically significant improvements in behavior and cognition
Behavioral disturbances in dementia are a source of considerable anxiety for carers and often lead to the difficult decision to institutionalize patients. These symptoms have long been treated with neuroleptic medications, which in some cases can diminish the quality of life among patients and carers because of the extra-pyramidal side effects (such as: muscle stiffness, slowness of movement, postural instability). Moreover, DLB patients often develop sensitivity reactions to such medications, which are associated with a two- to three-fold increase in mortality.2,3
In the study, the core psychiatric symptoms of DLB were significantly reduced in patients treated with Exelon, compared with those receiving placebo. Patients in the Exelon group were less apathetic and had less anxiety, delusions and hallucinations while on treatment. Approximately twice as many patients taking Exelon (more than 60%) showed at least a 30% improvement from baseline in such symptoms than did placebo-treated patients.4
The study therefore suggests that Exelon may be a viable alternative to neuroleptic medications in the treatment of behavioral disturbances in DLB.
DLB patients treated with Exelon also showed marked improvement in objective measures of cognitive functioning, particularly in tests of attention and memory; such improvements were significantly greater than those observed in patients treated with placebo.4
"Based on these results, treatment with Exelon may help physicians meet the numerous therapeutic challenges associated with this patient population," added Dr. McKeith.
Similarity of DLB to Alzheimer's Disease
DLB shares many characteristics with Alzheimer's disease, including behavioral and cognitive disturbances related to a cholinergic deficit, which is caused by a decreased amount of the neurotransmitter, acetylcholine. Results from the DLB study support earlier findings from a study with Alzheimer's patients in nursing homes, experiencing behavioral symptoms. This open-label study showed that patients treated with Exelon for a period of more than six months experienced improvements over baseline Neuropsychiatric Inventory (NPI) scores on several behavioral symptoms. More than 50% of these Alzheimer's disease patients were able to discontinue neuroleptic therapy for behavioral disturbances.5
The study reported in The Lancet is the first double-blind, placebo-controlled study with a cholinesterase inhibitor in patients with DLB. A total of 120 DLB patients from Italy, Spain and the UK were enrolled. Patients were treated with up to 12 mg of Exelon or placebo per day for 20 weeks. Assessments were made using the Neuropsychiatric Inventory (NPI), the Cognitive Drug Research (CDR) computerized assessment system and a battery of neuropsychological tests.
Exelon is approved in more than 70 countries, including all of Europe, the US and Canada6. The medication is a potent brain-selective dual cholinesterase inhibitor for the treatment of mild to moderately severe Alzheimer's disease (AD)7. Exelon works by inhibiting two enzymes – acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). This dual inhibition reduces the breakdown of acetylcholine in the brain, thus optimizing cholinergic function.
Exelon is the first Alzheimer's medication to show clinical benefits in the US and Europe for all three key symptom areas, including activities of daily living (e.g., eating, dressing and completing household chores), global function (including behavior) and cognition (including thinking, memory and speaking). It has a low potential for drug-drug interactions, a particularly important consideration, as the average AD patient often takes many medications simultaneously. The most common side effects are gastro-intestinal in nature and are generally transient and mild to moderate in intensity.
1 Perry, RH, Irving D, Blessed G, Fairbairn A, Perry EK. Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci 1990; 95: 119-39.
2 McKeith I, Fairbairn A, Perry R, Thompson P, Perry E. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. Br Med J 1992; 305: 673–8.
3 Piggott MA, Perry EK, McKeith IG, Marshall E, Perry RH. Dopamine D2 receptors in demented patients with severe neuroleptic sensitivity. Lancet 1994; 343: 1044–5.
4 McKeith et al. Efficacy of rivastigmine in dementia with Lewy bodies: results of a randomised placebo-controlled international study. Lancet 2000; vol. 356, iss. 9248
5 Cummings J, Anand R, Koumaras, B and Hartman R: Rivastigmine provides behavioral benefits to Alzheimer's disease patients residing in a nursing home: findings from a 26-week trial [abstract]. Neurology. 2000; 54 (suppl 3): A468-A469. Abstract S79.002.
6 Full precribing information, EU labeling; indicated for mild to moderate Alzheimer's disease in the US and Canada
7 Exelon marketing authorisation does not include the indication of dementia with Lewy bodies.