Brexpiprazole

In the United States and Canada, brexpiprazole is indicated as an adjunctive therapy to antidepressants for the treatment of major depressive disorder and for the treatment of schizophrenia. In May 2023, the indication for brexpiprazole was expanded in the US to include the treatment of agitation associated with dementia due to Alzheimer's disease. ==Side effects==

The most common adverse events associated with brexpiprazole (all doses of brexpiprazole cumulatively greater than or equal to 5% vs. placebo) were upper respiratory tract infection (6.9% vs. 4.8%), akathisia (6.6% vs. 3.2%), weight gain (6.3% vs. 0.8%), and nasopharyngitis (5.0% vs. 1.6%). Brexpiprazole can cause impulse control disorders. ==Pharmacology==

Pharmacodynamics It exerts its pharmacodynamic actions mainly by modulating signaling of multiple serotonin, dopamine and noradrenaline receptors. Brexpiprazole acts as a partial agonist of the serotonin 5-HT1A receptor and the dopamine D2 and D3 receptors. Brexpiprazole is a less stimulating partial agonist of the dopamine receptors than its predecessor, aripiprazole, potentially decreasing its risk for agitation and restlessness. In vivo characterization of brexpiprazole shows that it may act as a near-full agonist of the 5-HT1A receptor. This may further underlie a lower potential than aripiprazole to cause treatment-emergent, movement-related disorders such as akathisia due to the downstream dopamine release that is triggered by 5-HT1A receptor agonism. It is also an antagonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT7 receptors, which may contribute to antidepressant effect. It also binds to and blocks the α1A-, α1B-, α1D-, and α2C-adrenergic receptors. It has also been identified as a potent vesicular monoamine transporter 2 (VMAT2) inhibitor ( = 22nM). ==History==

Clinical trials Brexpiprazole was in clinical trials for adjunctive treatment of major depressive disorder, adult attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease. Phase III A phase III study was in the recruiting stage: "Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial)". Its goal is "to compare the effect of brexpiprazole to the effect of placebo (an inactive substance) as add on treatment to an assigned FDA approved antidepressant treatment (ADT) in patients with major depressive disorder who demonstrate an incomplete response to a prospective trial of the same assigned FDA approved ADT". Estimated enrollment was 1250 volunteers. Adult attention deficit hyperactivity disorder • Attention Deficit/Hyperactivity Disorder (STEP-A) Schizophrenia Phase I • Trial to Evaluate the Effects of OPC-34712 (brexpiprazole) on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder Phase II • A Dose-finding Trial of OPC-34712 in Patients With Schizophrenia Phase III • Efficacy Study of OPC-34712 in Adults With Acute Schizophrenia (BEACON) • Study of the Effectiveness of Three Different Doses of OPC-34712 in the Treatment of Adults With Acute Schizophrenia (VECTOR) • A Long-term Trial of OPC-34712 in Patients With Schizophrenia Agitation associated with dementia due to Alzheimer's disease The effectiveness of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease was determined through two 12-week, randomized, double-blind, placebo-controlled, fixed-dose studies. In these studies, participants were required to have a probable diagnosis of Alzheimer's dementia; have a score between 5 and 22 on the Mini-Mental State Examination, a test that detects whether a person is experiencing cognitive impairment; and exhibit the type, frequency, and severity of agitation behaviors that require medication. Trial participants ranged between 51 and 90 years of age. ==Society and culture==

Legal status In January 2018, it was approved for the treatment of schizophrenia in Japan. Economics In November 2011, Otsuka Pharmaceutical and Lundbeck announced a global alliance. Patents • • WIPO PCT/JP2006/317704 • Canadian patent: 2620688 ==Research==

Brexpiprazole was under development for the treatment of attention deficit hyperactivity disorder (ADHD) as an adjunct to stimulants, but was discontinued for this indication. It reached phase II clinical trials for this use prior to discontinuation. == References ==