Donepezil, a medication commonly prescribed for Alzheimer’s disease, affects REM sleep primarily by increasing the amount and intensity of REM sleep, which can lead to changes in dreaming and sleep patterns. It works by inhibiting acetylcholinesterase, an enzyme that breaks down acetylcholine, thereby increasing acetylcholine levels in the brain. Since acetylcholine is a key neurotransmitter involved in promoting REM sleep, donepezil’s enhancement of cholinergic activity tends to boost REM sleep duration and intensity.
More specifically, donepezil can cause an increase in vivid dreaming and sometimes unusual or intense dreams. This is because REM sleep is the stage of sleep most closely associated with dreaming, and donepezil’s cholinergic enhancement amplifies the brain activity during this phase. Some patients report more frequent awakenings during the night or disrupted sleep due to these intensified dreams. In some cases, donepezil has been linked to REM sleep behavior disorder (RBD), a condition where the normal muscle paralysis during REM sleep is lost, leading to dream enactment behaviors such as talking, shouting, or even physical movements during sleep.
The timing of donepezil administration can influence its effects on sleep. It is typically taken in the evening before bedtime to align with its side effects like nausea and dizziness, but this timing can also exacerbate sleep disturbances related to REM sleep. Some clinicians may recommend taking it earlier in the day if sleep disruption becomes problematic, aiming to reduce the impact on REM sleep and dreaming.
At a neurochemical level, donepezil’s increase of acetylcholine enhances the activation of brain regions involved in REM sleep generation, such as the pontine tegmentum and basal forebrain. This cholinergic stimulation promotes the initiation and maintenance of REM sleep episodes, increasing their frequency and duration. However, this can sometimes lead to an imbalance in sleep architecture, where REM sleep becomes disproportionately increased relative to other stages of sleep, potentially affecting overall sleep quality.
In addition to altering REM sleep quantity, donepezil may affect REM sleep quality by influencing muscle atonia, the natural paralysis that prevents acting out dreams. In some individuals, this atonia is reduced, which can manifest as REM sleep behavior disorder. This side effect is more commonly observed in patients with underlying neurodegenerative conditions, such as Lewy body dementia, where cholinergic systems are already compromised.
The impact of donepezil on REM sleep is complex and varies among individuals. While some experience enhanced REM sleep and more vivid dreams without significant disruption, others may suffer from sleep fragmentation or parasomnias related to REM sleep. Adjusting the dose or timing of donepezil can sometimes mitigate these effects, but careful monitoring is necessary.
Overall, donepezil’s effect on REM sleep is a direct consequence of its cholinergic enhancement, which promotes REM sleep but can also lead to increased dreaming, altered muscle atonia, and potential sleep disturbances. Understanding these effects is important for managing patients on donepezil, especially those who report sleep-related side effects or have pre-existing sleep disorders.
