Brexpiprazole as an augmentation agent to antidepressants in treatment resistant major depressive disorder

ABSTRACT

Introduction: Approximately 50% of adults with major depressive disorder (MDD) who receive a first-line antidepressant treatment, at an appropriate dose, do not achieve an adequate response. Brexpiprazole is a novel serotonin-dopamine activity modulator in the second generation/atypical antipsychotic class that was approved by the United States Food & Drug Administration in 2015 for use as an adjunctive agent in the treatment of MDD inadequately responsive to antidepressant treatment. In general, second generation/atypical antipsychotics are widely used in the treatment of treatment resistant depression with brexpiprazole providing preliminary evidence for broad-spectrum efficacy across multiple domains affected by MDD, providing a basis for further elucidating its mechanistic effects to inform novel drug discovery.

Areas covered: The review herein presents the evidence base for the use of brexpiprazole as an augmentation agent to antidepressants in individuals with treatment resistant MDD, including its efficacy, safety, and tolerability profile.

Expert opinion: Brexpiprazole has been demonstrated to be effective and safe to use as an augmentation agent to antidepressant treatment among individuals with treatment resistant MDD due to its considerably improved tolerability profile when compared to other second generation/atypical antipsychotics; however, it is important to exercise clinical judgment when selecting disparate augmentation agents on a case-by-case basis weighing individual risks versus benefits

KEYWORDS:

• Brexpiprazole
• major depressive disorder
• second generation antipsychotic
• atypical antipsychotic
• major depressive disorder
• treatment resistance
• dopamine
• serotonin

Article highlights

• Replicated evidence shows that brexpiprazole as an augmentation agent to antidepressant treatment reduces depressive symptoms in those who do not initially respond to antidepressant treatment

• Brexpiprazole is taken as a once-daily oral medication

• Brexpiprazole has been demonstrated to improve a variety of symptoms associated with MDD (e.g. anxiety, irritability, sleep disturbance) as well as other measures of general function (e.g. social life, family life/home responsibilities, work/school)

• Brexpiprazole is a novel serotonin-dopamine activity modulator with lower intrinsic D₂ activity and higher 5-HT_1A/2A receptor binding affinity when compared to aripiprazole

• Safety data indicate that augmentation with brexpiprazole in MDD is generally well tolerated with commonly reported adverse events involving moderate weight gain and akathisia in a small proportion of patients

• This box summarizes key points contained in the article

Declaration of interest

D Cha has received Royalties from Oxford University Press and Cambridge University Press and has also received honorarium from Lundbeck. RS McIntyre has been on advisory boards and/or received honoraria for educational activities and/or research grants from Neurocrine, Sunovion, Janssen, Allergan, Lundbeck, Pfizer, Shire, Purdue, and Otsuka. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has previously acted a consultant for: Allergan, Lundbeck, Sunovion and Takeda. They have also received research support from Allergan and speaker’s bureau for Allergan, Lundbeck, Otsuka, Sunovion and Takeda. The reviewer is also a shareholder in: Centers of Psychiatric Excellence (COPE) and Global Medical Education. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.