Proven Efficacy
Reduction in Overall Depressive Symptoms as an Antidepressant Add-On for MDD1,2
MADRS total score reduction for VRAYLAR + ADT vs placebo + ADT1,2
6-week fixed-dose study (N=751)
8-week flexible-dose study (N=808)
| Duration | N | Design | Doses Studied | Control | Primary Endpoint |
| 6-Week | 751 | Fixed Dose | 1.5 mg/day + ADT; 3 mg/day + ADT |
Placebo + ADT | Mean change from baseline in MADRS total score at the end of Week 6 |
| 8-Week | 808 | Flexible Dose | 1-2 mg/day + ADT; 2-4.5 mg/day + ADT Mean VRAYLAR dose was 2.6 mg/day |
Placebo + ADT | Mean change from baseline in MADRS total score at the end of Week 8 |
Both adjunctive MDD studies were randomized, double-blind, placebo-controlled, and evaluated the efficacy and safety of VRAYLAR in adult patients (mean age of 45 years, range 18-65 years) who met DSM-IV-TR or DSM-5 criteria for MDD, with or without symptoms of anxiety, and had an inadequate response to 1 to 3 courses of prior antidepressant (ADT) therapy.§
In each study, the primary endpoint was mean change from baseline to Week 6 (fixed-dose study) or Week 8 (flexible-dose study) in the MADRS total score. Fixed-dose (N=751) was a 6-week trial involving 2 fixed doses of VRAYLAR (1.5 mg/day or 3 mg/day) + ADT vs placebo + ADT. Flexible-dose (N=808) was an 8-week trial involving flexible doses of VRAYLAR (1-2 mg/day or 2-4.5 mg/day) + ADT vs placebo + ADT, with a mean dose of 2.6 mg/day.
§Inadequate response during antidepressant treatment was defined as less than 50% improvement to antidepressant treatment of adequate dose and duration.
Most patients had moderate to severe depressive symptoms at baseline with ADT
Baseline mean MADRS total scores:
6-Week MDD Trial (pooled) = 32.5
VRAYLAR 1.5 mg/day + ADT = 32.8
VRAYLAR 3 mg/day + ADT = 32.7
Placebo + ADT = 31.9
8-Week MDD Flexible-Dose Trial
VRAYLAR 1-2 mg/day + ADT = 28.8
VRAYLAR 2-4.5 mg/day + ADT = 29.3
Placebo + ADT = 28.9
Across both MDD studies, about 70% of patients had inadequate response to their first antidepressant therapy in the current episode
In the 6-week fixed-dose MDD study, 83% of patients had anxiety symptoms at baselineII
Patients enrolled were taking the most commonly used antidepressants, including¶:
- sertraline
- fluoxetine
- bupropion
- escitalopram
- duloxetine
- citalopram
- desvenlafaxine
- venlafaxine
||Overall, 83% of patients had anxiety symptoms at baseline, defined as a score of ≥7 at baseline on the HAM-D anxiety/somatization factor. Anxiety/somatization factor comprises the following 6 items from the HAM-D; psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight.
¶These are not all of the ADTs patients were taking prior to and during the VRAYLAR MDD studies. Please see publications for complete list.2
ADT=antidepressant therapy; DSM=Diagnostic and Statistical Manual of Mental Disorders; LS= least squares; MADRS=Montgomery-Asberg Depression Rating Scale; MDD=major depressive disorder; NS= Not significant; TR=text revision.
Post-hoc analysis#
Range of MADRS Total Score Improvement from Baseline to Week 63 **
Observed reduction in MADRS total score by nearly 50% for:
- 46% of patients taking VRAYLAR 1.5 mg/day + ADT
- 35% of patients taking placebo + ADT
These analyses were not prespecified endpoints and were not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant.
A post-hoc analysis of data from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo (n=249), VRAYLAR 1.5 mg/day + ADT, or VRAYLAR 3 mg/day + ADT (n=502). The primary efficacy parameter was change from baseline at 6 weeks in MADRS total score and was analyzed using an MMRM approach.
#This was a post-hoc analysis of the primary endpoint (MADRS change from baseline to Week 6) and was not adjusted for multiple comparisons.
**The primary endpoint was change from baseline to Week 6 in MADRS total score. Results of a representative, pivotal, multicenter, randomized, placebo-controlled 6-week trial in adults with MDD (N=751). Patients were randomized in 3 arms: cariprazine 1.5 mg, cariprazine 3 mg, or placebo + ongoing ADT.1,2
mITT=modified intent-to-treat; MMRM=mixed-effects model for repeated measures.
Post-hoc analysis††
Observed Reduction in Individual Item Scores at Week 62‡‡
MADRS Items (Scored 0-6)
These analyses were not prespecified endpoints and were not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant.
A post-hoc analysis of data from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo + ADT (n=249), VRAYLAR 1.5 mg/day + ADT, or VRAYLAR 3 mg/day + ADT (n=502). The primary efficacy parameter was change from baseline at 6 weeks in MADRS total score and was analyzed using an MMRM approach.
††This was a post-hoc analysis of the primary endpoint (MADRS change from baseline to Week 6) and was not adjusted for multiple comparisons.
‡‡The primary endpoint was change from baseline to Week 6 in MADRS total score. Results of a representative, pivotal, multicenter, randomized, placebo-controlled 6-week trial in adults with MDD (N=751). Patients were randomized in 3 arms: cariprazine 1.5 mg, cariprazine 3 mg, or placebo + ongoing ADT.1,2
Post-hoc analysis
Change From Baseline in MADRS Total Score in MDD Patients With or Without Anxiety Symptoms2§§
These analyses did not assess the effect of treatment on symptoms of anxiety.
These analyses were not prespecified endpoints and were not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant.
A post-hoc analysis of data from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo + ADT (n=249), VRAYLAR 1.5 mg/day + ADT, or VRAYLAR 3 mg/day + ADT (n=502). The primary efficacy parameter was change from baseline at 6 weeks in MADRS total score and was analyzed using an MMRM approach.
Overall, 83% of patients had anxiety symptoms at baseline, defined as a score of ≥7 at baseline on the HAM-D anxiety/somatization factor. Anxiety/somatization factor comprises the following 6 items from the HAM-D: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight.
§§The primary endpoint was change from baseline to Week 6 in MADRS total score. Results of 1 pivotal, multicenter, randomized, placebo-controlled 6-week trial in adults with MDD (N=751). Patients were randomized in 3 arms: VRAYLAR 1.5 mg, VRAYLAR 3 mg, or placebo + ongoing ADT. This was a post-hoc analysis of the primary endpoint (MADRS change from baseline to Week 6) and was not adjusted for multiple comparisons.1,2