Effects of aripiprazole adjunctive to standard antidepressant treatment on the core symptoms of depression: a post-hoc, pooled analysis of two large, placebo-controlled studies.
BACKGROUND
Although antipsychotic agents have a long history of use in depression, their effectiveness in treating core symptoms of depression such as loss of interest has been questioned. Adjunctive aripiprazole is beneficial for the treatment of patients with major depressive disorder but its effects on specific symptoms have not been reported. The objective of this study was to examine the effects of aripiprazole on core symptoms of depression.


METHODS
This is a post-hoc, pooled analysis of two trials of aripiprazole augmentation of standard antidepressants (ADT) in patients with major depression. Patients with an inadequate response to ADT received adjunctive aripiprazole (n=373) or placebo (n=368) for 6 weeks. Change on four subscales of the 17-item Hamilton Depression Rating Scale (HAM-D17) that capture core depression symptoms was determined and change on individual HAM-D items also was assessed. The magnitude of within-group change for the subscales and individual items was expressed as effect size (ES) and between-group significance tested with ANCOVA. The magnitude of change was also examined comparing the response rates for aripiprazole and placebo on HAM-D17 and the four subscales. Change on three composite subscales - anxiety, insomnia and drive was also examined.


RESULTS
Within-group change on the four core subscales was substantial (ES=1.1-1.2) and similar to that for the 17-item HAM-D total score. Between-group comparisons indicated mean change and response rates were significantly greater with adjunctive aripiprazole than placebo for each core subscale (all p<0.01). Individual HAM-D17 items showing the greatest change from baseline with adjunctive aripiprazole: depressed mood (within-group ES=1.03) work and activities (ES=0.86), guilt (ES=0.77) and psychic anxiety (ES=0.67) are the same symptoms identified by each of the core subscales and each of these items differed significantly from change on that item with placebo (p<0.01). On three composite scales, adjunctive aripiprazole was significantly more effective than placebo with respect to mean change for anxiety, insomnia and drive (all p<0.001).


CONCLUSIONS
Aripiprazole augmentation of standard ADT results in significant, clinically meaningful changes in the core symptoms of depression. It is also associated with significant change in anxiety, insomnia, and drive components of the 17-item HAM-D.
Nelson
J Craig
JC
University of California, San Francisco, California, USA. craign@lppi.ucsf.edu
Mankoski
Raymond
R
Baker
Ross A
RA
Carlson
Berit X
BX
Eudicone
James M
JM
Pikalov
Andrei
A
Tran
Quynh-Van
QV
Berman
Robert M
RM
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D000068180:Aripiprazole; D003511:Cyclohexanols / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000453:epidemiology; D011795:Surveys and Questionnaires; D000069470:Venlafaxine Hydrochloride
D014150:Antipsychotic Agents; D000068180:Aripiprazole; D003511:Cyclohexanols; D010879:Piperazines; D015363:Quinolones; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride