Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder.
BACKGROUND
Due to their favorable side effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Aripiprazole, an atypical antipsychotic agent with partial dopaminergic and serotonin 1A receptor agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study was to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI).


METHODS
12 patients (mean +/- SD age = 46.6 +/- 11.3 years, 66.7% female) with major depressive disorder (MDD) diagnosed by use of the Structured Clinical Interview for DSM-IV-Axis I Disorders, who had failed to experience a clinical response following an adequate trial of an SSRI, were treated with open-label aripiprazole in addition to their SSRI for 8 weeks. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline-endpoint) as measured by the 17-item Hamilton Rating Scale for Depression total score. Data were collected from August 2003 to July 2004.


RESULTS
9/12 (75.0%) patients completed the trial. Using a completer analysis, 5/9 (55.6%) patients were classified as responders. An intent-to-treat (ITT) analysis resulted in 7 responders (58.3%). The overall proportion of remitters was 3/9 (33.3%) using a completer analysis and 5/12 (41.7%) using the ITT analysis. Aripiprazole administration appeared safe, with no severe adverse events observed in any of the study participants.


CONCLUSIONS
These results suggest a possible augmentation role for aripiprazole when used in conjunction with SSRIs in SSRI-resistant MDD.
Papakostas
George I
GI
Department of Psychiatry, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. gpapakostas@partners.org
Petersen
Timothy J
TJ
Kinrys
Gustavo
G
Burns
Alana M
AM
Worthington
John J
JJ
Alpert
Jonathan E
JE
Fava
Maurizio
M
Nierenberg
Andrew A
AA
D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D000068180:Aripiprazole; D010879:Piperazines; D015363:Quinolones; D017367:Selective Serotonin Reuptake Inhibitors