Idebenone - A review of its use in mild to moderate Alzheimer's disease

Idebenone is a benzoquinone derivative which is structurally related to ubiquinone, a component of the respiratory chain. Although the precise mechanism of action of the drug is unknown, preclinical studies suggest that idebenone amy exert cytoprotective properties by acting as a free radical scavenger. In addition, it also appears to improve cerebral metabolism, correct neurotransmitter defects and enhance memory and learning. Oral idebenone appears to improve cognitive function and behavioural deficits in patients with mild to moderate Alzheimer's disease. In 2 large double-blind placebo-controlled trials, idebenone 270 or 360 mg/day for up to 12 months produced a mean improvement of 1.6 to 3.9 points in the total score of the Alzheimer's Disease Assessment Scale (ADAS-Total) relative to placebo. After 12 months of treatment, improvements in ADAS-Total versus baseline were 10.3% with placebo, 14.7% with idebenone 270 mg/day and 19.6% with idebenone 360 mg/day. 34.1% of patients treated with idebenone 360 mg/day were judged to have improved when assessed according to measures of cognition, behaviour and clinician-rated global outcome measures. Notably, patients with a lesser degree of cognitive impairment (ADAS-Total <20) appear less likely to benefit from idebenone therapy. Idebenone was well tolerated when administered for up to 12 months to patients with Alzheimer's disease, and no significant changes in vital signs or laboratory values were reported. Thus, although comparisons with other agents are currently lacking, available data suggest the idebenone will be a useful therapeutic option for the management of Alzheimer's disease. Because of their different mechanisms of actions, combination therapy with idebenone and a cholinesterase inhibitor may also be a possibility in the future. However, studies are necessary to assess the feasibility of such an approach for the treatment of Alzheimer's disease.