Brexpiprazole

Brand Name:

Rexulti

Drug Class: 

Dopamine Partial Agonist

How it works:

It is a partial dopamine receptor 2 agonist. This theoretically increases dopamine when concentrations are low (helpful for depression) and decreases dopamine when concentrations are high (helpful for psychosis). This is more of a dopamine antagonist but has more potent action at the serotonin sub-types: 5HT-2A and 5HT-1A as compared to the similar medication, Aripiprazole.

What makes it unique: 

This was the first partial dopamine agonist. Sometimes called a “third-generation antipsychotic” because of its differences from other antipsychotics. This medication is only approved for use in depression as an add on to another medication such as an SSRI or SNRI. This medication has a long half-life, which means that it can stay in the body for a long time. This can be good, if a dose is forgotten, but can be bad if a side effect occurs.

Side effects: 

Some side effects include, headache, dizziness, insomnia, somnolence, nausea, anxiety, fatigue. This seems to cause less akathisia than Aripiprazole. Additional side effects include weight gain, metabolic changes, leukopenia, neutropenia, agranulocytosis, seizures and syncope. It can also cause pathological gambling and other compulsive behaviors.

This medication carries a risk of suicidal thinking and behavior in people age 24 and younger when used with an antidepressant medication.

How effective is it:

(1) A study looked at 1,056 patients with major depressive disorder who had inadequate response to antidepressant treatment. Adjunctive Brexpiprazole showed greater efficacy at week 2 as compared to adjunctive placebo. Brexpiprazole had clinically meaningful improvements in the MADRS depression scale in this study.

(2) A study looked at Brexpiprazole treatment as an adjunctive medication in patients who had an inadequate response to 1-3 antidepressant medications. 175 patients were given brexpiprazole 2mg and 178 patients were given a placebo. MADRS score decreased by 8.36 points in the treatment group as compared to 5.15 in the placebo group. The most common side effects in the treatment group were weight gain and akathisia.

Clinical experience: 

I don’t see this medication all that much. Since it works so similarly to Aripiprazole, most prescribers will probably try the more familiar Aripiprazole first. Pharmaceuticals should never be used as the sole treatment for mental illnesses. Therapy, exercise, meditation or other treatments should always accompany prescriptions.

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References:

1. Nelson J, Weiller E, Zhang P, et al. Efficacy of adjunctive brexpiprazole on the core symptoms of major depressive disorder: A post hoc analysis of two pooled clinical studies. J Affect Disord. 2018 Feb;227:103-108.

2. Thase M, Youakim J, Skuban A, et al. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry. 2015 Sep;76(9):1224-31.

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