Objectives: Second-generation (atypical) antipsychotics have been accepted as an adjunctive medication in patients with treatment-resistant depression. This clinical trial evaluated the efficacy and safety of low-dose aripiprazole combined with regular-dose sertraline for acute major depressive episode in non-treatment-resistant depression outpatients.
Methods: The study patients were 18- to 65-year-old outpatients fulfilling the criteria of major depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The patients were randomly assigned to 2 groups: one with sertraline 50 mg/d plus aripiprazole 2.5 mg/d and the other with sertraline 50 mg/d plus placebo. After baseline assessment, the subjects were followed up at weeks 1, 2, 4, 6, and 10. The primary efficacy was the score change of the 17-item Hamilton Rating Scale for Depression (HAM-D17), and secondary efficacies were the score of Short Form 36 Health Survey, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. This study also monitored patients for movement disorder using Simpson-Angus Scale and Barnes Akathisia Rating Scale.
Results: Twenty-one patients were assigned to the aripiprazole group and 20 to the placebo group. Because of high dropout rate, only data of the first 4 weeks were analyzed. The aripiprazole group exhibited significantly better efficacy than the placebo group in mean total score changes of HAM-D17 from the baseline to weeks 1, 2, and 4. The item "work and social activities" of HAM-D17 showed significant improvement at week 2, and the item "somatic symptoms (GI)" showed significant improvement at week 1. The aripiprazole group exhibited significant improvement in "social role function" section of Short Form 36 Health Survey at week 4. The mean total score of Clinical Global Impressions-Severity showed marginally significant improvement in the aripiprazole group. In Clinical Global Impressions-Improvement, patients in the aripiprazole group had scores of less than 2 (much improved) at weeks 2 and 4, and the scores of the placebo group were greater than 2.4 (indicating a minimal improvement). No patients had akathisia during the trial period.
Conclusions: The primitive data showed that adjunctive low-dose aripiprazole could augment the efficacy of regular-dose sertraline in fresh major depressive disorder. A large-scale study is needed to confirm this finding.