Brexpiprazole (Rexulti®)

The United States Food and Drug Administration (FDA) approved

brexpiprazole (brand name “Rexulti®”) in July 2015 for two indications:

the treatment of schizophrenia and as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). Rexulti® is manufactured by Otsuka Pharmaceutical Company Ltd and co-marketed with H. Lundbeck A/S.

Pharmacological effects

1. Partial agonist at the 5HT1A, D2, and D3 receptors

2. Antagonist at 5HT2A, 5HT2B, 5HT7, alpha-1A, alpha-1B, alpha-1D, and alpha-2C receptors.

Dosing

1. For adjunctive treatment of major depressive disorder, the recommended starting dosage for is 0.5 mg or 1 mg once daily, followed by titration up to the target dosage of 2 mg once daily. The maximum recommended daily dosage is 3 mg.

2. For the treatment of schizophrenia,the recommended target dose is 2 mg to 4 mg once daily. The recommended starting dosage is 1 mg once daily on Days 1 to 4, 2 mg once daily on Day 5 through Day 7, and then 4 mg once daily from Day 8 onwards.

Dosage adjustments are recommended for patients who are poor metabolizers on the CYP450 2D6 isoenzyme and those taking strong inducers/ inhibitors of CYP2D6 and/or CYP3A4.

Dosage forms and strengths

Rexulti® is available as tablets in the following dosage strengths: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg

What are the differences in the pharmacological activity of brexpiprazole and aripiprazole? What were the hypothesized advantages that may result from these differences?

1. Brexpiprazole has lower intrinsic activity for partial agonism at D2 receptors. It was hypothesized that this may lead to a lower potential to cause adverse effects that are mediated through agonism of D2 receptors, i.e., akathisia, insomnia, restlessness, and nausea.

2. Brexpiprazole was also hypothesized to have a lower potential to adverse effects that are mediated through D2 antagonism, i.e., parkinsonism, hyperprolactinemia.

3. Brexpiprazole has similar (“balanced”) potency at D2, 5-HT1A, and 5-HT2A receptors. It was hypothesized that this may also contribute to lower incidences of activation adverse effects and D2 antagonism associated adverse effects.

Please refer to Prescribing Information (see link below) for complete discussion of dosage, administration, warnings and precautions, contraindications, etc.

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References

Prescribing information for brexpiprazole (Rexulti®)

Review Articles

Citrome L. Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic – what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2015 Sep;69(9):978-97. PubMed PMID: 26250067.

Citrome L. The ABC’s of dopamine receptor partial agonists – aripiprazole, brexpiprazole and cariprazine: the 15-min challenge to sort these agents out. Int J Clin Pract. 2015 Nov;69(11):1211-20. PubMed PMID: 26477545.

Goff DC. Brexpiprazole: A New Antipsychotic Following in the Footsteps of Aripiprazole. Am J Psychiatry. 2015 Sep 1;172(9):820-1. PubMed PMID: 26324298.

Randomized, placebo-controlled clinical trials in schizophrenia

Correll CU, Skuban A, Ouyang J, Hobart M, Pfister S, McQuade RD, Nyilas M, Carson WH, Sanchez R, Eriksson H. Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial. Am J Psychiatry. 2015 Sep 1;172(9):870-80. PubMed PMID: 25882325.

Kane JM, Skuban A, Ouyang J, Hobart M, Pfister S, McQuade RD, Nyilas M, Carson WH, Sanchez R, Eriksson H. A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia. Schizophr Res. 2015 May;164(1-3):127-35. PubMed PMID: 25682550.

Randomized, placebo-controlled clinical trials of adjunctive use in major depressive disorder