A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole for the treatment of acute manic or mixed episodes in Asian patients with bipolar I disorder (the AMAZE study)

Abstract

Objectives. To investigate the efficacy and safety of aripiprazole in Asian patients with manic or mixed episodes associated with bipolar I disorder. Methods. Subjects were randomised to aripiprazole (24 mg/day; reduced to 12 mg/day if needed for tolerability; n = 128) or placebo (n = 130) for 3 weeks in this multicentre, double-blind study. The primary efficacy measure was mean change from baseline in Young Mania Rating Scale (YMRS) Total score. Results. A total of 136 patients (aripiprazole 56.3%; placebo 49.2%) completed the study. The majority of patients (92.6%) received aripiprazole 24 mg/day. Aripiprazole produced statistically significant mean improvements in YMRS Total scores compared with placebo from Day 4 through to Week 3 (–11.3 vs. –5.3; P < 0.001). The most common adverse events (> 15% of patients; aripiprazole vs. placebo) were akathisia (22.0 vs. 5.6%) and insomnia (16.3 vs. 9.6%). Aripiprazole treatment resulted in no significant difference from placebo in change in mean body weight from baseline (–0.4 vs. –0.7 kg; P = 0.231). Aripiprazole was not associated with an elevated serum prolactin level. Conclusions. Aripiprazole had significantly greater efficacy than placebo for the treatment of acute manic or mixed episodes associated with bipolar I disorder in Asian patients. Treatment was generally safe and well tolerated.

Key words::

• Bipolar I disorder
• aripiprazole
• efficacy
• safety
• Asian study

Acknowledgements

This study was supported by 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 Otsuka Pharmaceutical Co., Ltd.

The authors would also like to thank the Principal Investigators in the AMAZE study group who were: Kimihiro Nakajima (Hokkaido, Japan), Shin Kashiwakura (Hokkaido, Japan), Norio Furukori (Aomori, Japan), Shinichi Niwa (Fukushima, Japan), Chikara Kumakiri (Fukushima, Japan), Itaru Miura (Fukushima, Japan), Hiroyuki Takagi (Gunma, Japan), Shingo Tatsumi (Saitama, Japan), Tasuku Hashimoto (Chiba, Japan), Tetsuro Enomoto (Chiba, Japan), Hirokazu Iwasaki (Chiba, Japan), Masaru Mimura (Tokyo, Japan), Tetsuo Nakabayashi (Tokyo, Japan), Yuichiro Tsutsumi (Tokyo, Japan), Jun Ishigooka (Tokyo, Japan), Takehiko Matsumura (Kanagawa, Japan), Yutaka Ushimi (Yokohama, Kanagawa, Japan), Itsuki Jibiki (Ishikawa, Japan), Hajime Oga (Aichi, Japan), Kiyoshi Fujita (Aichi, Japan), Takeshi Shimoyama (Mie, Japan), Atsushi Mori (Mie, Japan), Naoto Yamada (Shiga, Japan), Masafumi Yoshimura (Osaka, Japan), Hideki Tanaka (Osaka, Japan), Hiroki Kikuyama (Osaka, Japan), Koji Toyonaga (Osaka, Japan), Miyuki Sadamatsu (Nara, Japan), Kazuyuki Ohara (Hyogo, Japan), Ken Watanabe (Tottori, Japan), Satoru Kamio (Tottori, Japan), Tsuruhei Sukegawa (Tottori, Japan), Satoshi Nishiyama (Tottori, Japan), Nobuyuki Okabe (Okayama, Japan), Yu Nakamura (Kagawa, Japan), Shinichi Sakata (Fukuoka, Japan), Yuichi Saeki (Saga, Japan), Tomokazu Yamamoto (Nagasaki, Japan), Kosuke Nishiyama (Kumamoto, Japan), Hajime Arakaki (Okinawa, Japan), Naoki Taira (Okinawa, Japan), Naohiko Asato (Okinawa, Japan), Takeshi Ashizawa (Hokkaido, Japan), Yasushi Sato (Aomori, Japan), Youichirou Takayanagi (Tokyo, Japan), Yoshiyuki Asai (Chiba, Japan), Atsuomi Baba (Kanagawa, Japan), Yoshihisa Shoji (Fukuoka, Japan), Tatsuya Ishigaki (Kanagawa, Japan), Kenichi Minamata (Akita, Japan), Ken Sawada (Kochi, Japan), Masaki Sanga (Gunma, Japan), Yoko Iwasaki (Hiroshima, Japan), Fan-Kwong Tsang (New Territories, Hong Kong), Yun Kwok Wing (New Territories, Hong Kong), Se Fong Hung (New Territories, Hong Kong), Sutantri (Central Java, Indonesia), Didit Roesono (East Java, Indonesia), Citra Julita Tarigan (Medan-North Sumatra, Indonesia), A. A. A. Agung Kusumawardhani (Central Jakarta, Indonesia), Chin-Bin Yeh and Wei-Wen Lin (former Principal Investigator), (Taipei, Taiwan), Yuan-Hwa Chou (Taipei, Taiwan), Shih-Ku Lin (Taipei, Taiwan), Ching-Yen Chen (Taoyuan, Taiwan), Chih-Ken Chen (Keelung, Taiwan), Nien-Mu Chiu (Kaohsiung, Taiwan), Yen-Kuang Yang (Tainan, Taiwan), Wen-Yu Hsu and Shaw-Hwa Jou (former Principal Investigator), (Changhua, Taiwan), Yu-Chih Shen, Chiao-Hsiang (former Principal Investigator), and Chaucer Lin (former Principal Investigator), (Hualien, Taiwan), Ding-Lieh Liao (Taipei, Taiwan), Niufan Gu (Shanghai, China), Qingrong Tan (Xi’an, China), Keqing Li (Baoding, China), Gang Wang (Beijing, China), Cui Ma (Guangzhou, China), Xiaoping Wang (Wuhan, China), Xiufeng Xu (Kunming, China), Jingping Zhao (Changsha, China), Shiping Xie (Nanjing, China), Hongyan Zhang (Beijing, China), Ahmad Hatim Sulaiman (Kuala Lumpur, Malaysia), Abdul Kadir Abu Bakar (Johor, Malaysia), Rosliwati Mohd Yusoff (Kuching, Sarawak, Malaysia), Mohd Ariff Mohd Noor (Kelantan, Malaysia), Cynthia Ramos-Leynes (Manila, Philippines), Efren B. Reyes (Mandaluyong City, Philippines), Agnes Padilla (Davao City, Philippines), Fe A. Costales (Cebu, Philippines), Constantine D. Della (Las Piñas City, Philippines), Josefina Ly-Uson (Pasig City, Philippines) and Rowena Cosca (Iloilo City, Philippines).

Statement of Interest

Shigenobu Kanba has received direct support from Otsuka; served as a consultant for Astellas and Otsuka; received grant/research support from GSK, Astellas and Dainippon-Sumitomo, and acted as an honoraria/speaker, attending advisory boards for GSK, Pfizer and Lilly, Japan. Hiroaki Kawasaki has received direct support from Otsuka. Jun Ishigooka has received direct support from Otsuka; served as a consultant for Otsuka and Dainippon-Sumitomo, and speaker at advisory boards for Otsuka and Dainippon-Sumitomo. Kaoru Sakamoto has received direct support from Otsuka. Toshihiko Kinoshita has received direct support from Otsuka; served as a consultant for Takeda and MSD; received grant/research support from GSK, and been a speaker at advisory boards for Pfizer, GSK, Lilly, Takeda, Meiji and Janssen. Toshihide Kuroki has received direct support from Otsuka.