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Efficacy and safety of aripiprazole once-monthly versus oral aripiprazole in Chinese patients with acute schizophrenia: a multicenter, randomized, double-blind, non-inferiority study

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Abstract

Objective

The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia.

Methods

This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10–20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions—Severity (CGI-S) scores, respectively.

Results

A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were − 33.6 for the AOM group and − 34.8 in the oral aripiprazole group, respectively, with a difference of − 1.2 (95% CI: − 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was − 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was − 2.2 and − 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively.

Conclusions

This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia.

Trial registration

ClinicalTrials.gov identifier: NCT03172871.

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References

  • Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, Yocca FD, Molinoff PB (2002) Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 302:381–389

    Article  CAS  Google Scholar 

  • Committee for Medicinal Products for Human Use (CHMP) (2014) Abilify Maintena EMA Public Assessment Report (EPAR). European Medicines Agency website. https://www.ema.europa.eu/en/documents/assessment-report/abilify-maintena-epar-public-assessmentreport_en.pdf

  • Fleischhacker WW, Sanchez R, Perry PP, Jin N, Peters-Strickland T, Johnson BR, Baker RA, Eramo A, McQuade RD, Carson WH, Walling D, Kane JM (2014) Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study. Br J Psychiatry 205:135–144

    Article  Google Scholar 

  • Giordano G, Tomassini L, Cuomo I, Amici E, Perrini F, Callovini G, Carannante A, Kotzalidis GD, De Filippis S (2020) Aripiprazole long-acting injection during first episode schizophrenia-an exploratory analysis. Front Psych 10:935

    Article  Google Scholar 

  • Haddad PM, Brain C, Scott J (2014) Non-adherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Relat Outcome Meas 5:43–62

    Article  Google Scholar 

  • Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller HJ (2013) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 14:2–44

    Article  Google Scholar 

  • Ishigooka J, Nakamura J, Fujii Y, Iwata N, Kishimoto T, Iyo M, Uchimura N, Nishimura R, Shimizu N, Group AS (2015) Efficacy and safety of aripiprazole once-monthly in Asian patients with schizophrenia: a multicenter, randomized, double-blind, non-inferiority study versus oral aripiprazole. Schizophr Res 161:421–8

    Article  Google Scholar 

  • Iwata N, Inagaki A, Sano H, Niidome K, Kojima Y, Yamada S (2020) Treatment persistence between long-acting injectable versus orally administered aripiprazole among patients with schizophrenia in a real-world clinical setting in Japan. Adv Ther 37:3324–3336

    Article  CAS  Google Scholar 

  • Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, Ali MW (2002) Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 63:763–771

    Article  CAS  Google Scholar 

  • Kane JM, Peters-Strickland T, Baker RA, Hertel P, Eramo A, Jin N, Perry PP, Gara M, McQuade RD, Carson WH, Sanchez R (2014) Aripiprazole once-monthly in the acute treatment of schizophrenia: findings from a 12-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 75:1254–1260

    Article  Google Scholar 

  • Kane JM, Schooler NR, Marcy P, Correll CU, Achtyes ED, Gibbons RD, Robinson DG (2020) Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: a randomized clinical trial. JAMA Psychiat 77:1217–1224

    Article  Google Scholar 

  • Kane JM, Correll CU (2019) Optimizing treatment choices to improve adherence and outcomes in schizophrenia. J Clin Psychiatry 80(5):IN18031AH1C

  • Kirson NY, Weiden PJ, Yermakov S, Huang W, Samuelson T, Offord SJ, Greenberg PE, Wong BJ (2013) Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry 74:568–575

    Article  CAS  Google Scholar 

  • Kishimoto T, Nitta M, Borenstein M, Kane JM, Correll CU (2013) Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry 74:957–965

    Article  Google Scholar 

  • Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, Borenstein M, Kane JM, Correll CU (2014) Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull 40:192–213

    Article  Google Scholar 

  • Kishimoto T, Hagi K, Kurokawa S, Kane JM, Correll CU (2021) Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies. Lancet Psychiatry 8:387–404

    Article  Google Scholar 

  • Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J (2004) Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 161:1–56

  • Lin CH, Chen FC, Chan HY, Hsu CC (2019) Time to rehospitalization in patients with schizophrenia receiving long-acting injectable antipsychotics or oral antipsychotics. Int J Neuropsychopharmacol 22:541–547

    Article  Google Scholar 

  • Marder SR, McQuade RD, Stock E, Kaplita S, Marcus R, Safferman AZ, Saha A, Ali M, Iwamoto T (2003) Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res 61:123–136

    Article  Google Scholar 

  • Naber D, Hansen K, Forray C, Baker RA, Sapin C, Beillat M, Peters-Strickland T, Nylander AG, Hertel P, Andersen HS, Eramo A, Loze JY, Potkin SG (2015) Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia. Schizophr Res 168:498–504

    Article  Google Scholar 

  • National Collaborating Centre for Mental Health (2009) National Institute for Health and Clinical Excellence: Guidance Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care (Update). British Psychological Society, National Collaborating Centre for Mental Health, Leicester

    Google Scholar 

  • Pandina GJ, Lindenmayer JP, Lull J, Lim P, Gopal S, Herben V, Kusumakar V, Yuen E, Palumbo J (2010) A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol 30:235–244

    Article  CAS  Google Scholar 

  • Remington G, Teo C, Mann S, Hahn M, Foussias G, Agid O (2013) Examining levels of antipsychotic adherence to better understand non-adherence. J Clin Psychopharmacol 33:261–263

    Article  Google Scholar 

  • Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P (2011) A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 168:603–609

    Article  Google Scholar 

  • Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, Docherty JP (2010) Strategies for addressing adherence problems in patients with serious and persistent mental illness: recommendations from the expert consensus guidelines. J Psychiatr Pract 16:306–324

    Article  Google Scholar 

  • Wakamatsu A, Aoki K, Sakiyama Y, Ohnishi T, Sugita M (2013) Predicting pharmacokinetic stability by multiple oral administration of atypical antipsychotics. Innov Clin Neurosci 10:23–30

    PubMed  PubMed Central  Google Scholar 

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Author information

Author notes

  1. Le Xiao and Qian Zhao contributed equally to this work.

Authors and Affiliations

  1. The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing, 100088, China

    Le Xiao, Qian Zhao, An-ning Li & Gang Wang

  2. Huzhou Third Municipal Hospital, Huzhou, China

    Jushui Sun

  3. Xi’an Mental Health Center, Xi’an, China

    Bin Wu

  4. Tianjin Mental Health Centre, Tianjin Anding Hospital, Tianjin, China

    Lina Wang

  5. Brain Hospital of Hunan Province, Changsha, China

    Honggeng Zhang

  6. Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China

    Ruiling Zhang

  7. Hebei Provincial Mental Health Center, Baoding, China

    Keqing Li

  8. Wuhan Mental Health Center, Wuhan, China

    Xiaojin Xu

  9. Shenzhen Mental Health Center, Shenzhen, China

    Tiebang Liu & Wenshun Zhang

  10. Nanjing Brain Hospital, Nanjing, China

    Shiping Xie

  11. First Affiliated Hospital of Kunming Medical University, Kunming, China

    Xiufeng Xu

  12. Beijing Huilongguan Hospital, Beijing, China

    Yunlong Tan

  13. First Hospital of Shanxi Medical University, Taiyuan, China

    Kerang Zhang

  14. Peking University Sixth Hospital, Beijing, China

    Hongyan Zhang

  15. The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Nianhong Guan

  16. Clinical Development, Otsuka Beijing Research Institute, Beijing, China

    Mingji Xian

  17. Division of Otsuka International Asia & Arab, Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan

    Motomichi Uki

Authors
  1. Le Xiao
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  2. Qian Zhao
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  6. Lina Wang
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  7. Honggeng Zhang
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  8. Ruiling Zhang
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  9. Keqing Li
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  10. Xiaojin Xu
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  16. Kerang Zhang
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  17. Hongyan Zhang
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  18. Nianhong Guan
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  19. Mingji Xian
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  20. Motomichi Uki
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  21. Gang Wang
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Corresponding author

Correspondence to Gang Wang.

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Conflict of interest

Dr. Gang Wang disclosed receipt of research funds from the National Key Research and Development Program of China (2016YFC1307200, 2017YFC1311100), the Capital’s Funds for Health Improvement and Research (2018–1-2121), and the Demonstration research ward of Beijing Health Committee (BCRW202009). Dr. Gang Wang had received research support from Pfizer and Merck & Co., Inc. Dr. Le Xiao and An-ning Li disclosed receipt of research funds from the National Natural Science Foundation (81901372; 81801322). Dr. Motomichi Uki is an employee of Otsuka Pharmaceutical Co., Ltd. Mingji Xian is an employee of Otsuka Beijing Research Institute. The other authors declare no conflict of interest concerning this article.

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Xiao, L., Zhao, Q., Li, An. et al. Efficacy and safety of aripiprazole once-monthly versus oral aripiprazole in Chinese patients with acute schizophrenia: a multicenter, randomized, double-blind, non-inferiority study. Psychopharmacology 239, 243–251 (2022). https://doi.org/10.1007/s00213-021-06044-x

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  • DOI: https://doi.org/10.1007/s00213-021-06044-x

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