Real-world effectiveness and safety of aripiprazole augmentation therapy in patients with major depressive disorder

Abstract

Aims: Augmentation therapy is an option for patients with major depressive disorder who do respond sufficiently to adequate dosages of selective serotonin reuptake inhibitors or serotonin–norepinephrine reuptake inhibitors, but little is known about application of this strategy in everyday practice.

Methods: This prospective, multi-center, observational study investigated the effectiveness and safety of aripiprazole augmentation in Japanese patients with inadequate response to conventional antidepressant therapy in real-world clinical practice. The primary endpoint was mean change in the (Japanese version) Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to study end. Safety was assessed by monitoring adverse events.

Results: There were 1103 patients in the safety population and 1090 patients in the effectiveness population. Mean change in the MADRS total score at study end was –14.9 ± 12.3 (p < .001 vs baseline). The remission rate increased from 34.5% at Month 6 to 43.3% at Month 12, suggesting additional benefit with continued treatment. The type of primary antidepressant (paroxetine, fluvoxamine, sertraline, milnacipran, duloxetine, mirtazapine, or escitalopram) had no influence on the effectiveness of aripiprazole augmentation therapy. A baseline MADRS total score of <33 points and an elapsed time of <176 days from an episode of depression to the start of aripiprazole treatment increased the likelihood of achieving remission; 24.8% of patients experienced at least one adverse event, but no new safety signals were identified.

Conclusions: Aripiprazole augmentation therapy appears to be effective and safe in Japanese patients with depression/depressive symptoms treated in everyday clinical practice, taking into account factors associated with achieving remission.

Keywords:

• Aripiprazole
• Augmentation therapy
• Depression
• Post-marketing surveillance
• Real world study

Transparency

Declaration of funding

The study was funded by Otsuka Pharmaceuticals Co., Ltd., Japan. Otsuka Pharmaceuticals Co., Ltd. has provided oversight on the conduct of the study, including design, collection, compilation, and analysis of data.

Declaration of financial/other interests

KK has received consulting fees from Otsuka Pharmaceutical Co. Ltd. MY, KY, and YF are fulltime employees of Otsuka Pharmaceuticals Co., Ltd. A CMRO peer reviewer on this manuscript declares consultancy for Eisai, Assurex, and Janssen. Other CMRO peer reviewers on this manuscript have no financial/other interests to disclose.

Acknowledgments

The authors wish to thank all investigators for their participation in the study. The authors also acknowledge Content Ed Net Ltd. for providing writing assistance, which was funded by Otsuka Pharmaceuticals Co., Ltd., Japan, and Mr Kunihiro Okashita, CMIC-PMS Co. Ltd. for statistical analysis.