Examination of nighttime sleep-related problems during double-blind, placebo-controlled trials of galantamine in patients with Alzheimer's disease

Background: Acetylcholinesterase inhibitors (AChEI) are now widely used as treatment for Alzheimer's disease (AD). Their cholinomimetic action has the potential to influence sleep quality and donepezil has been associated with sleep-related adverse events. This study examined whether galantamine, an AChEI with nicotinic modulation, is associated with nighttime sleep-related problems. Methods: Using data combined from three randomized, double-blind trials, galantannine (GAL) and placebo-treated patients were compared on sleep-related adverse events and concomitant medications. Verbatim descriptions by patients, as recorded by physicians, were used to classify adverse events into insomnia/sleep problems and nightmares/dreams. New concomitant medications were counted when prescribed for sleep-related indications. Treatment arms were 705 subjects on GAL 24 mg (12 mg BID), 279 on GAL 16 mg (8 mg BID), and 714 on placebo. Results: Comparing GAL 24, GAL 16, and placebo arms, the respective rates for insomnia/ sleep problems were 2.6, 1.1, and 2.2% and for nightmares were 1.1, 0.4, and 0.1%. Comparisons between GAL arms and placebo were not significant, with the exception of GAL 24 for nightmares (p = 0.02). However, due to the low frequency of nightmares in each group the clinical relevance of this difference is unknown. Rates of use for all concomitant medications indicated for sleep were 5.4, 2.9, and 4.6%, respectively, with no significant differences between GAL arms and placebo. Conclusion: These results support previous findings from double-blind, placebo-controlled studies that have shown maintenance of good sleep hygiene during treatment with galantamine.