A randomized, double-blind, placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan

Abstract

Objective This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD).

Research design and methods Patients aged 18–64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression–Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses.

Clinical trial registration This study has the www.japic.or.jp identifier: JapicCTI-121842.

Results For the primary efficacy endpoint, the difference from placebo in the LSAS-J was −3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of −9.8 (p < 0.001). In pre-specified sensitivity analyses, the difference versus placebo was −4.9 (p = 0.035) (ANCOVA, FAS, OC) and −5.0 (p = 0.028) (MMRM, FAS) (escitalopram 10 mg) and −10.1 (p < 0.001) (ANCOVA, FAS, OC) and −10.6 (p < 0.001) (MMRM, FAS) (escitalopram 20 mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder.

Conclusion Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics.

Keywords:

• Escitalopram
• Japan
• Liebowitz Social Anxiety Scale Japanese version (LSAS-J)
• Randomized placebo-controlled study
• Social anxiety disorder (SAD)

Declaration of funding

Mochida Pharmaceutical Co. Ltd sponsored the study and was involved in the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.

Author contributions: All authors designed the original study and wrote the protocol. T.H. monitored study progress. A.H. undertook the statistical analysis. All authors contributed to and have approved the final manuscript.

Declaration of financial/other relationships

T.H. and A.H. have disclosed that they are employees of Mochida Pharmaceutical Co. Ltd. S.A. and T.K. have disclosed that they served as medical experts for this clinical study. The expenses in preparing this paper were met by Mochida Pharmaceutical Co. Ltd.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

We thank the following investigators for their participation in this study: Dr. Hiroki Ishikawa, Dr. Masahiko Fujita, Dr. Kunihiko Kawamura, Dr. Kyoko Kawaharata, Dr. Kimihiro Nakajima, Dr. Takeshi Fujita, Dr. Michihiro Shimode, Dr. Motomichi Shimizu, Dr. Ken-ichi Harada, Dr. Hideo Maeda, Dr. Junko Shiraki, Dr. Keiji Kaneta, Dr. Naofumi Kusaka, Dr. Shun-ichi Munakata, Dr. Hirofumi Kanome, Dr. Yoshinori Watanabe, Dr. Masatoshi Yaginuma, Dr. Toshiaki Shichijo, Dr. Hiroshi Nagao, Dr. Masaharu Asakawa, Dr. Hisashi Miyake, Dr. Masataka Noguchi, Dr. Gaku Ishikawa, Dr. Shojiro Takahashi, Dr. Il Bong Lee, Dr. Kenji Shigemori, Dr. Satoshi Nakamura, Dr. Eiji Yoshida, Dr. Hiroko Sakamoto, Dr. Jun Matsushima, Dr. Takuji Hishinuma, Dr. Masami Tanaka, Dr. Naoki Harikae, Dr. Nobutoshi Kariya, Dr. Isao Fukunishi, Dr. Jun-ichi Aoki, Dr. Naohiro Yokoyama, Dr. Masaki Kishiro, Dr. Ken-ichi Goto, Dr. Yasutaka Tawara, Dr. Kotaro Kudo, Dr. Takashi Hayama, Dr. Hiroaki Harai, Dr. Keiichi Tanaka, Dr. Tokuji Hokuto, Dr. Yuji Ikeuchi, Dr. Kiyoshi Kohduki, Dr. Takashi Taguchi, Dr. Kenji Tatsuta, Dr. Masanori Kyo, Dr. Seigen Gon, Dr. Norihide Ensako, Dr. Osamu Yamamoto, Dr. Seiichi Tsuji, Dr. Tokumi Fujikawa, Dr. Soichiro Hirayama, Dr. Akio Mantani, Dr. Norio Yokota, Dr. Hiroshi Yamaguchi, Dr. Masamiki Kimura, Dr. Nobuhiko Imato, Dr. Hiromitsu Kaku, Dr. Naoyuki Hamada, Dr. Kazuhide Takada, Dr. Hideyo Sugahara, Dr. Masaru Yoshimura, Dr. Junko Hatakeyama, Dr. Hikari Mizuma, Dr. Hiroaki Furui, Dr. Kaori Hamada, Dr. Masahiro Matsunaga, Dr. Tetsuya Tachiyama, Dr. Joji Kobayashi, Dr. Naoki Kojima, Dr. Hideaki Sakai, Dr. Kunio Kato, Dr. Tetsuo Abe, Dr. Masanobu Takeuchi, Dr. Taihei Fukuhara, Dr. Akihiro Kakishima, Dr. Yoko Ueda, Dr. Masashi Yoshida, Dr. Takashi Furune, Dr. Kahori Ito, and Dr. Naoshige Matsuguchi.