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When taken with an antidepressant,
REXULTI® (brexpiprazole) amplified antidepressant symptom response in patients with MDD experiencing partial response
Primary endpoint—change in MÅDRS score
Primary endpoint—change in MÅDRS score
an=379 patients with confirmed partial response to ADT + single-blind placebo. Persistent partial response criteria (prospective phase) included: <50% reduction in HAM-D17 total score and ≥14 HAM-D17 score at Week 8; <50% reduction in MÅDRS total score and Clinical Global Impression-Improvement Score of ≥3 at each scheduled visit.1,4
*p<0.05, **p<0.01, ***p<0.001 vs placebo. MÅDRS before prospective treatment (SD): 31.0 (4.7).2 MÅDRS after prospective treatment (SD): 27.1 (5.7).2 MÅDRS at randomization (SD): ADT + placebo (n=178), 27.3 (5.6); ADT + REXULTI 2 mg/day (n=175), 26.9 (5.7).
ADT, antidepressant therapy; HAM-D17, 17-item Hamilton Depression Rating Scale; MÅDRS, Montgomery-Åsberg Depression Rating Scale.
Mean change from baseline across two pivotal trials
At the 2-mg/day recommended dose, the mean change from baseline (SE) at 6 weeks (randomized phase) was -8.4 (0.6) for ADT + REXULTI vs -5.2 (0.6) for ADT + placebo (-3.2 [95% CI: -4.9, -1.5], p=0.0002).1,b At the 3-mg/day maximum dose, the mean change from baseline (SE) at 6 weeks (randomized phase) was -8.3 (0.5) for ADT + REXULTI vs -6.3 (0.5) for ADT + placebo (-2.0 [95% CI: -3.4, -0.5], p=0.0079).4 At the 3-mg dose, the MÅDRS baseline (SD) for ADT + REXULTI (n=213) and ADT + placebo (n=203) was 26.5 (5.3) and 26.5 (5.2), respectively.4
bDose statistically significantly superior to placebo.
Study design summary
REXULTI was studied in two 6-week, double-blind, placebo-controlled, fixed-dose pivotal trials of adult patients meeting DSM-IV-TR criteria for MDD. After a screening phase of 1-4 weeks, patients who met inclusion criteria were treated with an SSRI or SNRI for 8 weeks. Patients who met criteria for persistent partial responsec to an 8-week prospective treatment with an antidepressant were randomized to receive adjunctive REXULTI. Approximately 49% of patients in the 2 trials had symptoms of anxiety at randomization.1,4,5,d
Primary endpoint was the mean change from baseline to Week 6 in the MÅDRS total score in the randomization phase1,4
cPersistent partial response criteria (prospective phase) included: <50% reduction in HAM-D17 total score and ≥14 HAM-D17 score at Week 8; <50% reduction in MÅDRS total score and Clinical Global Impression-Improvement Score of ≥3 at each scheduled visit.1,4
dPresence of anxiety symptoms was defined by a HAM-D anxiety/somatization factor of ≥7.4.6
DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision); SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Full study design
REXULTI® (brexpiprazole)—full MDD study design
1.
1-4 weeks
Screening—patients with partial response to antidepressant treatment entered the clinical trial with1,4:
- Partial response to 1 to 3 courses of antidepressant treatment in current episode
- MDD ≥8 weeks’ duration
- HAM-D17 score ≥18
- <50% reduction in symptoms via ATRQ
Study 1 (N=1227), Study 2 (N=2310)
2.
8 weeks
Prospective phase—clinical investigators initiated a different antidepressant treatment (+ single-blind placebo) at optimal dose and duration to confirm persistent partial response1,4,a
SSRIs
Escitalopram
Sertraline
Paroxetine CR
Fluoxetine
10 or 20 mg/day
100, 150, or 200 mg/day
37.5 or 50 mg/day
20 or 40 mg/day
SNRIs
Duloxetine DR
Venlafaxine XR
40 or 60 mg/day
75, 150, or 225 mg/day
Study 1 (N=826), Study 2 (N=1532)1,4
3.
6 weeks
Randomized double-blind phase—patients with confirmed partial response were randomized to add REXULTI or remain on antidepressant treatment alone (+ placebo)1,4
Study 11 (n=379)
ADT + REXULTI
2 mg/day (n=175)c
ADT + Placebo
(n=178)c
Study 24,b (n=677)
ADT + REXULTI
3 mg/day (n=213)c
ADT + Placebo
(n=203)c
Study 1 (N=826), Study 2 (N=1532)1,4
Titration—all patients randomized to REXULTI initiated treatment at 0.5 mg/day during Week 1. At Week 2, the REXULTI dose was increased to 1 mg/day and either maintained at 1 mg/day or increased to 2 mg/day or 3 mg/day, based on treatment assignment, from Week 3 onward.
Primary endpoint—change from baseline to Week 6 in MÅDRS in the randomization phase1,4
MÅDRS clinician-rated symptoms7:
- Apparent sadness
- Reported sadness
- Lassitude
- Inability to feel
- Inner tension
- Inner tension
- Reduced appetite
- Reduced sleep
- Concentration difficulties
- Pessimistic thoughts
- Suicidal thoughts
- Pessimistic thoughts
- Suicidal thoughts
aPersistent partial response criteria (prospective phase) included: <50% reduction in HAM-D17 Total Score and ≥14 HAM-D17 score at Week 8; <50% reduction in MÅDRS Total Score and Clinical Global Impression-Improvement Score of ≥3 at each scheduled visit.1,4
bThe efficacy and safety of REXULTI 1 mg/day were also studied in Study 2 (n=211).
cn values represent efficacy population per final protocol.1,4
ATRQ, Antidepressant Treatment Response Questionnaire; CR, controlled release; DR, delayed release; HAM-D17, 17-Item Hamilton Depression Rating Scale; MÅDRS, Montgomery-Åsberg Depression Rating Scale; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; XR, extended release.
Contraindication
In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.
In a post hoc analysis,
Adding REXULTI® (brexpiprazole) amplified antidepressant symptom response in patients with MDD — with and without symptoms of anxiety8,a
Changes in MÅDRS total score were evaluated in patients with MDD—with and without symptoms of anxiety—using pooled data from three similarly designed 6-week randomized studies, including both 2 mg and 3 mg doses1,4,8-10,b
Patients with symptoms of anxiety
Patients without symptoms of anxiety
Patients with symptoms of anxiety
Patients without symptoms of anxiety
- In patients with or without symptoms of anxiety, adjunctive REXULTI demonstrated reductions in mean MÅDRS total score at the 2-3 mg/day dose
For patients with symptoms of anxiety, the LS mean change at Week 6 between ADT + REXULTI 2-3 mg/day and ADT + placebo was -2.19 (95% CI: -3.60 to -0.78), p=0.00238
For patients without symptoms of anxiety, the LS mean change at Week 6 between ADT + REXULTI 2-3 mg/day and ADT + placebo was -2.34 (95% CI: -3.58 to -1.10), p=0.00028
aPresence of anxiety symptoms was defined by a HAM-D anxiety/somatization factor of ≥7.6
bBaseline demographics and clinical characteristics were similar between treatment subgroups; however, patients with symptoms of anxiety were more likely to be female and have a higher MÅDRS total score at baseline compared with patients without symptoms of anxiety (both p<0.0001).8
†p<0.05.
‡p<0.01.
§p<0.0001 vs placebo.
LS, least squares.
Important Warning and Precaution for Cerebrovascular Adverse Events, Including Stroke
In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.
BETTER TOGETHER: REXULTI + Antidepressants
for patients with MDD experiencing partial response
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