Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder

Abstract

Background:

Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting.

Patients and methods:

Patients (n = 706) completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296) nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received open-label aripiprazole for up to 52 weeks.

Results:

Open-label treatment was completed by 323 patients (32.2%). At endpoint (n = 987), the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients) spontaneously reported adverse events were akathisia (26.2%), fatigue (18.0%), and weight gain (17.1%). The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%); all resolved within 45 days of drug discontinuation. Mean weight change was 4.4 kg; 36.6% experienced ≥7% increase in weight from baseline (observed case analysis, n = 303). No clinically relevant changes in other metabolic parameters were seen. At the end of open-label treatment, 221 patients (69.7%) had a Clinical Global Impression-Severity of Illness score of 1 (not at all ill) or 2 (borderline ill).

Conclusion:

Long-term adjunctive aripiprazole therapy was well tolerated with an acceptable long-term safety and tolerability profile in patients with major depressive disorder who had not responded to treatment with one or more antidepressant therapies. Clinically significant weight gain was observed in about one-third of patients. Overall, the adverse event profile was consistent with that reported in the short-term trials and readily managed clinically.

Keywords:

• adjunctive aripiprazole
• antidepressant therapy
• major depressive disorder
• long-term safety and tolerability

Acknowledgements

The authors would like to thank Stephen R Wisniewski for his contributions to the analysis and interpretation of data and Gary Hyman for assistance with protocol design.

Disclosure

This study was supported by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Co, Ltd (Tokyo, Japan). Editorial support for the preparation of this manuscript was provided by Ogilvy Healthworld Medical Education; funding was provided by Bristol-Myers Squibb. MT has received research support from, served as a consultant to, or has been on the speakers’ boards of the following: Abdi Brahim, Abbott Laboratories Inc, Akzo (Organon Pharmaceuticals Inc), AstraZeneca, Bayer, Bristol-Myers Squibb, Cephalon Inc, Corcept Therapeutics Inc, Cyberonics Inc, Eli Lilly & Company, Fabre Kramer Pharmaceuticals Inc, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Meade Johnson, Merck, National Institute of Mental Health, National Alliance for Research in Schizophrenia and Depression, Neuronetics, Novartis, Parke-Davis Pharmaceuticals Inc, Pfizer Inc, Pharmacia and Upjohn, Predix Pharmaceuticals, Sepracor, Solvay Pharmaceuticals Inc, VantagePoint, and Wyeth-Ayerst Laboratories.

MET has been an advisor/consultant for Adolar, Astra-Zeneca, Bristol-Myers Squibb Company, Cyprus Pharmaceuticals, DaiNippon, Eli Lilly & Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson, Lundbeck, MedAvante Inc, Mensante, Merck (including Organon/Schering Plough), Novartis, Pamlab, PGx, Otsuka, Pfizer (including Wyeth), Pharmaneuroboost, Shire US Inc, Takeda, and Transcept. MET has received honoraria for talks from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Company, Pfizer (including Wyeth), and Shionogi. He has also received grant funding from Forest Laboratories, Eli Lilly & Company, GlaxoSmithKline, the National Institute of Mental Health, and Otsuka, and has equity holdings in MedAvante Inc, and has received royalties from American Psychiatric Publishing Inc, Guildford Publications, and Herald House.

RMB, SM, JAH, RNM, and RAB are employees of Bristol-Myers Squibb. RM and WC are employees of Otsuka Pharmaceutical Development and Commercialization Inc.