General Information

Rexulti (brexpiprazole) is an atypical antipsychotic.

Rexulti is specifically indicated:

for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults

for the treatment of schizophrenia in adults and pediatric patients ages 13 years and older

Rexulti is supplied as a tablet for oral administration. The recommended dose is as follows:

Major Depressive Disorder: the recommended starting dose is 0.5 mg or 1 mg once daily, taken orally with or without food. Titrate to 1 mg once daily, then up to the target dosage of 2 mg once daily. Dosage increases should occur at weekly intervals based on the patient’s clinical response and tolerability. The maximum recommended daily dosage is 3 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment.

Schizophrenia (Adults): the recommended starting dose is is 1 mg once daily on Days 1 to 4, taken orally with or without food. The recommended target dosage is 2 mg to 4 mg once daily. Titrate to 2 mg once daily on Day 5 through Day 7, then to 4 mg on Day 8 based on the patient’s clinical response and tolerability. The maximum recommended daily dosage is 4 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment.

Schizophrenia (Pediatrics 13 to 17 years of age): the recommended starting dose is 0.5 mg/day. The recommended maintenance dose is 2 to 4 mg/day and the maximum dose is 4 mg/day.

Mechanism of Action

Rexulti (brexpiprazole) is an atypical antipsychotic. The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.

Side Effects

Adverse effects associated with the use of Rexulti may include, but are not limited to, the following:

akathisia

weight gain

Rexulti comes with a black box warning of increased mortality in elderly patients with dementia-related psychosis; and a potential risk in the increase of the risk of suicidal thoughts and behaviors in patients aged 24 years and younger.

Clinical Trial Results

Adjunctive treatment for Major Depressive Disorder:

The efficacy of Rexulti in the adjunctive treatment of major depressive disorder (MDD) was evaluated in two 6-week, double-blind, placebo-controlled, fixed-dose trials of adults meeting DSM-IV-TR criteria for MDD, with or without symptoms of anxiety, who had an inadequate response to prior antidepressant therapy (1 to 3 courses) in the current episode and who had also demonstrated an inadequate response throughout the 8 weeks of prospective antidepressant treatment. In Study 228 (Study 1) subjects were randomized to Rexulti 2 mg once a day or placebo. In Study 227 (Study 2) subjects were randomized to Rexulti 1 or 3 mg once a day or placebo. For subjects randomized to Rexulti, all subjects initiated treatment at 0.5 mg once daily during Week 1. At Week 2, the Rexulti dosage was increased to 1 mg in all treatment groups, and either maintained at 1 mg or increased to 2 mg or 3 mg once daily, based on treatment assignment, from Week 3 onwards. The dosages were then maintained for the 4 remaining weeks. The primary endpoint was change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-related scale used to assess the degree of depressive symptomatology, with 0 representing no symptoms, and 60 representing worst symptoms. At randomization, the mean MADRS total score was 27. In both studies adjunctive brexpiprazole showed greater improvement than adjunctive placebo in MADRS total score at Week 6 in the efficacy population per final protocol in Study 1 (2mg+ADT [N=175]: -3.21, p=0.0002), and in Study 2 (1mg+ADT [N=211]: -1.30, p=0.0737; 3mg+ADT [N=213]: -1.95, p=0.0079). Similar results were observed for the efficacy population in both studies. The completion rate was high (>90%) and comparable across brexpiprazole and placebo groups.

Schizophrenia:

The efficacy of Rexulti in the treatment of adults with schizophrenia was demonstrated in two 6-week, randomized, double-blind, placebo-controlled, fixed-dose clinical trials in subjects who met DSM-IV-TR criteria for schizophrenia. In both studies, Study 231 (Study 3) and Study 230 (Study 4), subjects were randomized to Rexulti 2 or 4 mg once per day or placebo. Subjects in the Rexulti groups initiated treatment at 1 mg once daily on Days 1 to 4. The Rexulti dosage was increased to 2 mg on Days 5 to 7. The dosage was then either maintained at 2 mg once daily or increased to 4 mg once daily, depending on treatment assignment, for the 5 remaining weeks. The primary efficacy endpoint of both trials was the change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score. In one study, brexpiprazole 4mg and 2mg demonstrated greater improvement than placebo in the primary endpoint of change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (4mg: -19.65, p=0.0006 and 2mg: -20.73, p=<0.0001 vs. placebo -12.01; 0.25mg was similar to placebo -14.90). In the other study, brexpiprazole 4mg showed improvement over placebo in the primary endpoint of PANSS Total Score from baseline to Week 6 (-20.0 vs. -13.5, p=0.0022), while the 2mg (-16.6) and 1mg (-16.9) doses showed numeric improvement versus placebo (-13.5, p>0.05).