Aprepitant for Harmful Irritability and Spontaneous Aggression in Dementia (AHIMSA-D)
University Health Network
Aggressive behaviour is a risky and burdensome symptom in many patients with dementia, and more effective, better-tolerated treatment options are needed. Studies in animals suggest that the brain’s mechanisms for regulating aggressive behaviour involve a neurotransmitter called substance P, via a receptor called neurokinin-1 (NK1). There is a n already-existing, Health Canada-approved medication for nausea that blocks the NK1 receptor, called aprepitant. Although many previous studies have shown this medication to be safe and effective against some kinds of nausea, so far it has never been studied as a treatment for aggressive behaviour. In this study, we will enroll 40 patients with dementia who have problematic aggressive behaviours. Each patient will receive 3 weeks of twice-daily aprepitant and then 3 weeks of placebo, or vice versa, in a crossover design
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
If successful, the study will demonstrate that an already-approved medication for nausea can achieve significant reductions in aggressive behaviour in patients with dementia. This would constitute a significant advance over existing treatment, as there are currently no medications specifically for aggressive behaviour, and current medications used to treat aggression off-label often carry significant adverse effects, especially in older people. A successful treatment for aggressive behaviour could allow patients with dementia and aggression who are currently hospitalized to be treated in a less institutional setting, and to be at less risk of harming themselves or other people.
This will be the first time that aprepitant has ever been studied as a medication for aggressive behaviour. Since the medication is already approved in Canada and known to be safe, well-tolerated, if the study is successful, it would be available for immediate use. For patients with dementia who have aggressive behaviours that keep them in institutional care, it could mean less risk to themselves or others, and potentially a chance to move to a less intensive care setting.