Behavioral and psychological symptoms of
dementia are symptoms of disturbed perception, mood, behavior, and thought content that occurred frequently. These symptoms, which include apathy, depression, anxiety,
psychosis, agitation, and aggression, can serve as predictors of and early clinical diagnostic markers for
Alzheimer's disease (AD) and are common precipitants of institutional care. Agitation and
psychosis are associated with accelerated
disease progression and increased tau phosphorylation in patients with AD. Current guidelines recommend the use of second-generation
antipsychotics for the treatment of agitation and
psychosis in AD, but only after first-line non-pharmacological interventions and for no longer than 12 weeks because long-term use of these drugs is associated with an increased risk of mortality and an increased frequency of cerebrovascular events. Therefore, new
antipsychotic drugs with improved efficacy and safety are needed as an alternative to current
antipsychotic drugs. In this report, we discuss some of the most relevant advances in the field of agitation and
psychosis in AD and focus on the recent positive clinical evidence observed with two new
antipsychotics drugs:
brexpiprazole and
pimavanserin.
Brexpiprazole is a receptor partial agonist (D2, D3,
5-HT1A), receptor antagonist (5-HT2A/B, α1B/α2C) according to the neuroscience-based nomenclature. Two recent phase III clinical trials have shown that
brexpiprazole 2 mg/day is effective for the treatment of agitation in patients with AD and has an improved tolerability and safety profile compared with currently available second-generation
antipsychotics.
Pimavanserin is a receptor antagonist (5-HT2A, 5-HT2C) that has been given market authorization for
psychosis occurring in
Parkinson's disease. Recent phase II studies suggest that this
drug is effective in AD patients with more severe
psychosis, although further long-term studies are needed to better define the efficacy and long-term safety profile of
pimavanserin for the treatment of
psychosis in AD.