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Efficacy and safety of quetiapine extended release monotherapy in bipolar depression: a multi-center, randomized, double-blind, placebo-controlled trial

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Abstract

Rationale

Quetiapine extended release (XR) has been used to treat various psychiatric disorders, including depressive episodes associated with bipolar I and II disorders. Quetiapine XR is the first approved drug in China for the treatment of bipolar disorder.

Objectives

The study evaluated the efficacy and safety of short-term quetiapine XR monotherapy in the treatment of depressive episodes of bipolar I and II disorders.

Methods

This was an 8-week multi-center, randomized, double-blind, placebo-controlled, fixed-dose phase 3 study. The primary endpoint was the mean change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary endpoints included Clinical Global Impressions-Bipolar (CGI-BP) and remission rates.

Results

The study recruited 279 adult bipolar I or II patients currently experiencing depression from 11 Chinese provinces. Of these, 139 received quetiapine XR (300 mg/day) and 140 received placebo for 8 weeks. The mean change in the MADRS total score was significantly greater in the quetiapine XR group than in the placebo group (−19.00 ± 7.88 vs. −16.20 ± 9.32; p = 0.004). Adverse events occurred in 96 patients (65.3 %) in the quetiapine XR group and 72 (49.0 %) in the placebo group. The incidence of serious adverse events did not differ significantly between the groups (p = 0.247).

Conclusions

This study, which is the first to evaluate 300 mg/day quetiapine XR monotherapy for depression in Chinese patients with bipolar disorders, found that this drug was superior to the placebo. Quetiapine XR was generally safe and well tolerated (ClinicalTrials.gov number, NCT01256177).

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Abbreviations

MADRS:

Montgomery-Åsberg Depression Rating Scale

XR:

Extended release

FDA:

Food and Drug Administration

AE:

Adverse event

FAS:

Full analysis set

PP:

Per-protocol

HAM-D:

Hamilton Rating Scale for Depression

YMRS:

Young Mania Rating Scale

MMRM:

Mixed-model repeated-measures

OC:

Observed cases

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Acknowledgments

The authors thank AstraZeneca for supplying the quetiapine XR and for allowing us to use the computer-based randomization system.

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Authors and Affiliations

  1. Shanghai Mental Health Center, No.600 South Wanping Road, Xuhui District, Shanghai, 200030, China

    Huafang Li & Niufan Gu

  2. Peking University Sixth Hospital, No.51 North Huayuan Rd., Haidian District, Beijing, 100191, China

    Hongyan Zhang & Xin Yu

  3. Beijing An Ding Hospital, Capital Medical University, No.5 An Kang Hutong Deshengmen wai, Xicheng District, Beijing, 100008, China

    Gang Wang

  4. Xijing Hospital, No.127 Changle West Road, Xi’an, 710032, Shanxi, China

    Qingrong Tan

  5. Beijing Huilongguan Hospital, Hui Long Guan, Changping District, Beijing, 100096, China

    Fude Yang

  6. Guangzhou Brain Hospital, No.36 Mingxin Road, Guangzhou, 510170, Guangdong, China

    Yuping Ning

  7. Brain Hospital of Hunan Province, No.427 Furong Zhonglu 3 duan, Changsha, 410007, Hunan, China

    Honggeng Zhang

  8. Tongji Hospital Affiliated to Tongji University, No.389 Xincun Road, Shanghai, 200065, China

    Zheng Lu

  9. The 1st Affiliated Hospital of Kunming Medical College, No.295 Xichang Road, Kunming, 650032, Yunnan, China

    Xiufeng Xu

  10. Xi’an Mental Health Center, No. 15 Yanyin Road Qujiang New District, Xi’an, 710061, Shanxi, China

    Jianguo Shi

  11. First Affiliated Hospital of Medical College of Xi’an Jiaotong University, No.277 Yanta West Road, Xi’an, 710061, Shanxi, China

    Chengge Gao

  12. Central South University Xiangya No 2 Hospital, No.139 Middle Renmin Road, Changsha, 410008, Hunan, China

    Lingjiang Li

  13. 1st Affiliated Hospital of Shan Xi Medical University, No.85 Jiefang South Road, Taiyuan, 030001, Shanxi, China

    Kerang Zhang

  14. Tianjin Anding Hospital, No.13 Liulin Road, Hexi District, Tianjin, 300222, China

    Hongjun Tian

  15. Renmin Hospital of Wuhan University, No.238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China

    Xiaoping Wang

  16. Hebei No.6 Hospital, No.572 Dongfeng East Road, Baoding, 071000, Hebei, China

    Keqing Li

  17. The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie Fang Road, Hangzhou, 100027, Zhejiang, China

    Huichun Li

  18. The First Affiliated Hospital of Medical School of Zhejiang University, No.58 Chengzhan Road, Hangzhou, 310003, Zhejiang, China

    Yi Xu

  19. Nanjing Brain Hospital, No.264 Guangzhou Road, Nanjing, 210029, China

    Shiping Xie

Authors
  1. Huafang Li
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  2. Niufan Gu
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  3. Hongyan Zhang
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  4. Gang Wang
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  5. Qingrong Tan
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  6. Fude Yang
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  7. Yuping Ning
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  8. Honggeng Zhang
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  9. Zheng Lu
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  10. Xiufeng Xu
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  11. Jianguo Shi
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  12. Chengge Gao
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  13. Lingjiang Li
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  14. Kerang Zhang
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  15. Hongjun Tian
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  16. Xiaoping Wang
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  17. Keqing Li
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  18. Huichun Li
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  19. Yi Xu
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  20. Shiping Xie
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  21. Xin Yu
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Corresponding author

Correspondence to Xin Yu.

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Li, H., Gu, N., Zhang, H. et al. Efficacy and safety of quetiapine extended release monotherapy in bipolar depression: a multi-center, randomized, double-blind, placebo-controlled trial. Psychopharmacology 233, 1289–1297 (2016). https://doi.org/10.1007/s00213-016-4215-z

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  • DOI: https://doi.org/10.1007/s00213-016-4215-z

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