Bipolar I Depression
Proven Antidepressant Efficacy for
Bipolar I Depressive Episodes
Bipolar I episodes and diagnosis
Significant change in MADRS total score in bipolar I depression studies1, 4-6
Study 7 (N=431)1,2,4
Study 8 (N=474)1,2,5
Study 9 (N=478)1,2,6
It is unknown if the statistically significant differences observed at time points earlier than Week 6 represent clinically relevant treatment effects.
Two 6-week and one 8-week randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of VRAYLAR in adult patients (18-65 years old) who met DSM-IV-TR and DSM-5 criteria for depressive episodes associated with bipolar I disorder. The primary statistical analyses were conducted using an MMRM approach. In each study, the primary endpoint was the LS mean change from baseline in MADRS total score at the end of Week 6.1,4-6
*Patients with nonmissing baseline and ≥1 postbaseline parameter assessment during the double-blind treatment period—Study 7: VRAYLAR 1.5 mg/day (n=4/145) and VRAYLAR 3 mg/day (n=4/145) compared to placebo (n=5/142); Study 8: VRAYLAR 1.5 mg/day (n=1/153) and VRAYLAR 3 mg/day (n=0/164) compared to placebo (n=2/157); Study 9: VRAYLAR 1.5 mg/day (n=2/162) and VRAYLAR 3 mg/day (n=0/154) compared to placebo (n=2/158).2
DSM=Diagnostic and Statistical Manual of Mental Disorders; LS=least squares; MADRS=Montgomery-Asberg Depression Rating Scale; MMRM=mixed-effects model for repeated measures; TR=text revision.
Post-hoc item analysis of pooled data from VRAYLAR pivotal bipolar I depression studies7
Observed reduction in all individual MADRS item scores at Week 67
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.
VRAYLAR was approved based on the primary endpoint, mean change in MADRS total score from baseline at Week 6.1
A post-hoc analysis of data pooled from 3 randomized, placebo-controlled, double-blind studies of adult patients with bipolar I disorder. Patients in the ITT population (N=1383) were treated with either placebo (n=460) or VRAYLAR (n=923). VRAYLAR doses 1.5–3 mg/day were pooled for analysis. Mean change from baseline at 6 weeks on individual MADRS items was analyzed using an MMRM approach.7
ITT= intent-to-treat
Change in functional outcomes
Additional efficacy endpoint in one pivotal bipolar I depression trial: Change in Functioning Assessment Short Test (FAST) total score at Week 82
These analyses were not prespecified endpoints and were not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant.
VRAYLAR was approved based on the primary endpoint, mean change in MADRS total score from baseline at Week 6.1
This 8-week, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of VRAYLAR in adult patients (18-65 years old) who met DSM-IV-TR criteria for depressive episodes associated with bipolar I disorder. The primary statistical analysis was conducted using an MMRM approach. The primary endpoint was the LS mean change from baseline in MADRS total score at the end of Week 6.1,2
SD=standard deviation; SE=standard error.
The FAST evaluates functional impairment8
The FAST is a clinician-rated scale designed to assess functional impairments in patients with bipolar I disorder. It consists of 24 items divided among 6 areas of functioning:
Autonomy
Capacity to do things alone and make their own decisions
Occupational functioning
Capacity to perform and succeed at work
Cognitive functioning
Capacity to concentrate, learn, and problem-solve
Financial issues
Capacity to manage and spend money responsibly
Interpersonal relationships
Capacity to maintain relationships and socialize
Leisure time
Capacity to pursue hobbies and other activities of leisure
Items are rated using a 4-point scale:
0=no difficulty; 1=mild difficulty; 2=moderate difficulty; 3=severe difficulty. The total score is the sum of all 24 items. The higher the score, the more serious the difficulties are.