title: Aripiprazole augmentation versus antidepressant switching for patients with major depressive disorder: A 6-week, randomized, rater-blinded, prospective study.
abstract: No study has directly compared the efficacy and tolerability of aripiprazole augmentation (AA) and antidepressant switching (SW) in patients with major depressive disorder (MDD). This is the first 6-week, randomized, rater-blinded, direct comparison study between AA and SW in outpatients. An inadequate response to antidepressants was defined as a total score ≥ 14 on the Hamilton Depression Rating Scale-item 17 (HDRS-17) despite adequate antidepressant dosage for at least 6 weeks in the current depressive episode. The primary endpoint was change in the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the end of treatment. Secondary efficacy measures included the response and remission rates as priori defined at the end of treatment: changes in total scores of the HDRS-17, Iowa Fatigue Scale (IFS), and Sheehan Disability Scale (SDS) from baseline to the end of treatment and the proportion of patients who scored 1 or 2 on the Clinical Global Impression-Improvement Score (CGI-I) at the end of treatment. Tolerability was assessed with the Barnes Akathisia Rating Scale (BARS) and Arizona Sexual dysfunction scale (ASEX), and the numbers of adverse events were compared between the two groups. A total of 101 patients were randomized to either AA (n = 52) or SW (n = 49). The mean change in the MADRS score from baseline was significantly higher in the AA, with a difference in magnitude of -8.7 (p < 0.0001). The intergroup difference was first evident in week 2. The numbers of responders (p = 0.0086) and remitters (p = 0.0005) were also significantly higher in the AA (60% and 54%, respectively) compared with the SW (32.6% and 19.6%, respectively). On most secondary endpoints, AA showed better clinical outcomes compared to SW. The tolerability profiles were comparable between the two groups. Overall, AA yielded potentially beneficial clinical outcomes compared to SW. Given the methodological shortcomings of the present study, adequately powered, more rigorously controlled clinical trials are strongly warranted to confirm the present findings.
authors.affiliation: Department of Psychiatry, College of Medicine, Korea University, Seoul, South Korea.
authors.forename: Changsu
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
authors.forename: Sheng-Min
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Dongguk University, Gyeongju, South Korea.
authors.forename: Kyung-Phil
authors.initials: KP
authors.lastname: Kwak
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
authors.forename: Wang-Yeon
authors.initials: WY
authors.lastname: Won
authors.affiliation: Department of Neuropsychiatry, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea.
authors.forename: HwaYoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Chang Gung Memorial Hospital at Linkuo, Taiwan.
authors.forename: Chia Ming
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, Kaohsiung Medical University Chung-ho Memorial Hospital, Taiwan.
authors.forename: Tze Chun
authors.initials: TC
authors.lastname: Tang
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Duram, NC, USA. Electronic address: pae@catholic.ac.kr.
authors.forename: Chi-Un
authors.initials: CU
authors.lastname: Pae
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D016037:Single-Blind Method; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000068180:Aripiprazole
keywords: Antidepressant; Aripiprazole; Augmentation; Major depressive disorder; Switching