A Study of Aripiprazole in Patients With Major Depressive Disorder

Conditions

Major Depressive Disorder

Keywords

Single or recurrent, non-psychotic episode of Major Depressive Disorder

Brief summary

The purpose of this 14 week, randomized, double-blind, placebo controlled study is to assess the safety and efficacy of aripiprazole to placebo as adjunctive treatment to an assigned open-label marketed antidepressant therapy (ADT) in patients with Major Depressive Disorder who demonstrate an incomplete response to a prospective eight week trial of the same assigned open-label marketed antidepressant therapy.

T. D. Stewart, Ainslie Hatch, Kimberly Largay, John J. Sheehan, Sabrina Marler et al. (7 authors)

Journal of Affective Disorders2014-03-2416 citations

10.1016/j.jad.2014.03.017

Improvement in functional outcomes with adjunctive aripiprazole versus placebo in major depressive disorder: a pooled post hoc analysis of 3 short-term studies.

Fabian TJ, Cain ZJ, Ammerman D, Eudicone JM, Tang Y, Rollin LM, Forbes RA, Berman RM, Baker RA.

2012-12-203 citations

10.4088/pcc.12m01394

Beneficial effects of adjunctive aripiprazole in major depressive disorder are not dependent on antidepressant therapy history: a post hoc analysis of 3 randomized, double-blind, placebo-controlled trials.

Dunner DL, Laubmeier KK, Manos G, Forbes RA, Baker RA, Berman RM.

2012-11-222 citations

10.4088/pcc.12m01380

Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response.

Casey DE, Laubmeier KK, Marler SV, Forbes RA, Baker RA.

2012-05-314 citations

10.4088/pcc.11m01251

Effects of adjunctive aripiprazole on sexual functioning in patients with major depressive disorder and an inadequate response to standard antidepressant monotherapy: a post hoc analysis of 3 randomized, double-blind, placebo-controlled studies.

Fava M, Dording CM, Baker RA, Mankoski R, Tran QV, Forbes RA, Eudicone JM, Owen R, Berman RM.

2011-01-0111 citations

10.4088/pcc.10m00994gre

Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants.

Berman RM, Fava M, Thase ME, Trivedi MH, Swanink R, McQuade RD, Carson WH, Adson D, Taylor L, Hazel J, Marcus RN.

2009-04-01179 citations

10.1017/s1092852900020216

Interventions

DRUGAripiprazole+ ADT

Tablets, Oral, 2 - 20 mg variable dose once daily, 14 weeks

DRUGPlacebo+ ADT

Tablets, Oral, 2 - 20 mg variable dose once daily, 14 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

DIAGNOSTIC

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

No

Inclusion criteria

* Men and women, 18-65 years old who have experienced single or recurrent, non-psychotic episodes of Major Depressive Disorder, with the current episode of minimally 8 weeks in duration. * Treatment history of an inadequate response to at least one and no more than three adequate antidepressant trials.

Design outcomes

Primary

Measure	Time frame	Description
Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS)	Baseline (Week 8) and Week 14	Mean change from Week 8 (baseline) to Week 14 in MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.

Secondary

Measure	Time frame	Description
Mean Change in SDS Item Score (Social Life)	Baseline (Week 8) and Week 14	Mean change from Week 8 (baseline) to Week 14 in SDS Social Life Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
Mean Change in Sheehan Disability Scale (SDS) Mean Score	Baseline (Week 8) and Week 14	Mean change from Week 8 (baseline) to Week 14 in SDS Mean Score, a 3-item, ordinal scale (0=unimpaired; 30=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
Mean Change in SDS Item Score (Family Life)	Baseline (Week 8) and Week 14	Mean change from Week 8 (Baseline) to Week 14 in SDS Family Life Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
Mean Change in SDS Item Score (Work/School)	Baseline (Week 8) and Week 14	Mean change from Week 8 (baseline) to Week 14 in SDS Work/School Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.

Other

Measure	Time frame	Description
MADRS Remission	Baseline (Week 8) and Week 14	Number of subjects in remission. Remission defined as as MADRS Total Score of \<10 at 14 weeks, and a reduction of ≥50 percent from Week 8 (baseline) in MADRS, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms).
Clinical Global Impression (CGI)-Improvement Response	Baseline (Week 8) and Week 14	Number of subjects with response relative to Week 8 (baseline). Response defined as score of 1 (very much improved) or 2 (much improved) on a 7-point, ordinal scale (1=very much improved; 7=very much worse).
MADRS Response	Baseline (Week 8) and Week 14	Number of subjects with a ≥50 percent reduction from Week 8 (baseline) in MADRS Total Score, a 10-item, ordinal rating scale to assess the severity of depressive symptoms (0=no symptoms; 60=most severe symptoms).

Countries

United States

Participant flow

Pre-assignment details

After initial screening period (7-28 days), subjects enrolled into an 8-wk prospective treatment phase (single-blind placebo plus an investigator-assigned, open-label, marketed antidepressant therapy \[ADT\]). Patients who met criteria for incomplete response at the end of this phase were randomized into the 6-wk double-blind phase in a 1:1 ratio.

Participants by arm

Arm	Count
Aripiprazole + ADT Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.	177
Placebo + ADT Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.	172
Total	349

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	11	3
Overall Study	Lack of Efficacy	2	3
Overall Study	Lost to Follow-up	3	2
Overall Study	marijuana use	0	1
Overall Study	pending surgery	0	1
Overall Study	Poor/noncompliance	3	4
Overall Study	Protocol Violation	5	2
Overall Study	Subject became unblinded	0	1
Overall Study	Withdrawal by Subject	6	6

Baseline characteristics

Characteristic	Placebo + ADT	Total	Aripiprazole + ADT
Age Continuous	45.6 years STANDARD_DEVIATION 11.3	45.4 years STANDARD_DEVIATION 10.9	45.1 years STANDARD_DEVIATION 10.6
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	12 Participants	6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	162 Participants	330 Participants	168 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants	7 Participants	3 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants	1 participants	0 participants
Race/Ethnicity, Customized Asian	2 participants	5 participants	3 participants
Race/Ethnicity, Customized Black or African American	18 participants	32 participants	14 participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants	1 participants	1 participants
Race/Ethnicity, Customized Unknown or Not Reported	2 participants	6 participants	4 participants
Race/Ethnicity, Customized White	149 participants	304 participants	155 participants
Sex: Female, Male Female	117 Participants	255 Participants	138 Participants
Sex: Female, Male Male	55 Participants	94 Participants	39 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	107 / 176	62 / 172
serious Total, serious adverse events	1 / 176	1 / 172

Outcome results

Primary

Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS)

Mean change from Week 8 (baseline) to Week 14 in MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.