Brexpiprazole is a potential treatment to reduce agitation and other behavioral symptoms in people with Alzheimer’s disease and Alzheimer’s-associated dementia. It is currently going through clinical testing in patients.

Co-developed by Otsuka Pharmaceutical and Lundbeck, brexpiprazole is approved by the U.S. Food and Drug Administration (FDA) to treat schizophrenia and as an add-on treatment for people with major depressive disorder. It is available under the brand name Rexulti.

How brexpiprazole works

The exact mechanism of action for brexpiprazole is still unknown. However, it is thought that it works by changing the levels of serotonin and dopamine, which are naturally available neurotransmitters in the brain.

Brexpiprazole in clinical trials

The safety, efficacy, and tolerability of brexpiprazole have been investigated in several clinical trials.

A Phase 3 clinical trial (NCT01862640) compared the efficacy of two fixed oral doses of brexpiprazole against placebo in people with agitation caused by Alzheimer’s disease-associated dementia.

Another Phase 3 randomized, double-blind, placebo-controlled trial (NCT01922258) evaluated the safety, efficacy, and tolerability of flexible dosing of brexpiprazole in a similar group of patients. Both were 12-week studies in people with a diagnosis of probable Alzheimer’s.

Top-line results from these studies, released in May 2017, revealed that treated patients showed improvements in symptoms of agitation relative to those given placebo. In both trials, which involved a combined total of around 700 patients, researchers measured improvements in agitation based on the variation in the Cohen-Mansfield agitation inventory (CMAI) total score, a 29-item scale that helps researchers to systematically evaluate the frequency of aggressive behaviors (physical and non-physical) and verbal agitation. Both studies also confirmed that brexpiprazole was well-tolerated and only mild side effects, such as insomnia, residual agitation, and somnolence (drowsiness), were reported by some patients.

Variability in data from different countries was evident, however, which the company reported might be associated with differences in standard of care.

A safety follow-up study (NCT02192554) observed about 450 of these patients for two months, without additional treatment. Results of this study are awaited.

Otsuka and Lundbeck announced that a new Phase 3 trial evaluating brexpiprazole as a potential treatment of agitation associated with dementia caused by Alzheimer’s disease would start in 2018. The planned trial, announced in October, followed discussions with the FDA regarding the earlier Phase 3 studies.

Otsuka and Lundbeck actually initiated 4 new trials in 2018. A 12-week double-blind, placebo-controlled trial testing 2 dosages of brexpiprazole against placebo (NCT03548584) will recruit approximately 225 patients in the US and Europe. A similar trial (NCT03620981), but for only 10 weeks, will recruit 407 patients in Japan. Both of these trials will have primary outcome measures of change from baseline in the CMAI. Following enrollment in these studies, patients can then be enrolled in a 12-week (NCT03594123 US and Europe) or 14-week extension (NCT03724942 Japan) of the studies to assess the longer-term safety of the drugs by monitoring adverse events. The trials are estimated to finish in late 2020 through late 2021.

Additional information

Brexpiprazole is also being tested as a potential treatment for people with attention deficit and hyperactivity disorder (ADHD).


Last updated: Aug. 19, 2019

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