沃替西汀辅助治疗双相抑郁发作的临床疗效和安全性

戴春晓; 付瑶阳; 励璇玮; 林美花; 李银波; 李潇; 黄可可; 周成成; 谢健; 赵青威; 胡少华

doi:10.1631/jzus.B2400470

Your Location：

Home >

Browse articles >

沃替西汀辅助治疗双相抑郁发作的临床疗效和安全性

Scan QR Code

文章被引用时，请邮件提醒。

Submit

Research Articles | Updated：2025-01-10

沃替西汀辅助治疗双相抑郁发作的临床疗效和安全性
Clinical efficacy and safety of vortioxetine as an adjuvant drug for patients with bipolar depression
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2025年26卷第1期页码：26-38
Affiliations：

1.Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310003, China
2.Department of Clinical Psychology, Hangzhou First People's Hospital, Hangzhou310006, China
3.Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310003, China
4.Fuyang Third People's Hospital, Hangzhou311402, China
5.Nanhu Brain-Computer Interface Institute, Hangzhou311100, China
6.The Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou310003, China
7.School of Brain Science and Brain Medicine, and MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou310012, China
8.Brain Research Institute of Zhejiang University, Hangzhou310003, China
9.The State Key Lab of Brain-Machine Intelligence, Zhejiang University, Hangzhou310003, China
10.Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou310003, China
Funds：

the Construction Fund of Key Medical Disciplines of Hangzhou(OO2020491);the National Key Research and Development Program of China(2023YFC2506200);the Zhejiang Provincial Key Research and Development Program(2021C03107);the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2023001B);the Leading Talent of Scientific and Technological Innovation‒“Ten Thousand Talents Program” of Zhejiang Province(2021R52016);the Innovation Team for Precision Diagnosis and Treatment of Major Brain Diseases(2020R01001);the Chinese Medical Education Association(2022KTZ004)
DOI：10.1631/jzus.B2400470
中图分类号：
CSTR：
纸质出版日期： 2025-01-15 ，

收稿日期： 2024-09-11 ，

修回日期： 2024-11-28 ，
Accepted：

戴春晓,付瑶阳,励璇玮等.沃替西汀辅助治疗双相抑郁发作的临床疗效和安全性[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(01):26-38.

CHUNXIAO DAI, YAOYANG FU, XUANWEI LI, et al. Clinical efficacy and safety of vortioxetine as an adjuvant drug for patients with bipolar depression. [J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(1): 26-38.
戴春晓,付瑶阳,励璇玮等.沃替西汀辅助治疗双相抑郁发作的临床疗效和安全性[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(01):26-38. DOI： 10.1631/jzus.B2400470.

CHUNXIAO DAI, YAOYANG FU, XUANWEI LI, et al. Clinical efficacy and safety of vortioxetine as an adjuvant drug for patients with bipolar depression. [J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(1): 26-38. DOI： 10.1631/jzus.B2400470.

摘要

沃替西汀作为辅助药物治疗双相抑郁的有效性尚存争议，因此本研究旨在验证沃替西汀治疗双相抑郁的有效性和安全性。这项前瞻性、双中心、随机和为期12周的临床试验共纳入100名双相Ⅱ型抑郁患者。主要观察指标为Montgomery-Asberg抑郁评定量表（MADRS），临床有效判定为MADRS减分率≥50%。所有符合条件的患者初期均接受4周鲁拉西酮单药治疗，其中治疗有效的患者继续接受该单一疗法，而无效患者被随机分配到联合丙戊酸盐或联合沃替西汀组，疗程为8周。通过综合比较4~12周的MADRS结果，系统分析沃替西汀是否可以作为辅助药物治疗双相抑郁。结果显示：37例患者对鲁拉西酮单药治疗有效，而无效的60例患者随机分为丙戊酸组和沃替西汀组，疗程8周；经丙戊酸或沃替西汀联合治疗2周后，沃替西汀组的MADRS评分明显低于丙戊酸组；两组在8周和12周时的MADRS评分没有差异；副作用发生率在丙戊酸组和沃替西汀组之间没有显著差异。重要的是，沃替西汀组中有3名患者转为躁狂或轻躁狂。本研究显示，鲁拉西酮联合沃替西汀对早期双相II型抑郁有潜在的益处，但我们应密切监测疾病进展，避免转躁风险。

Abstract

Objective

Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.

Methods

Patients with bipolar Ⅱ depression were enrolled in this prospective

two-center

randomized

12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However

no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks

a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.

Results

Thirty-seven patients responded to lurasidone monotherapy

and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment

the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly

three patients in the vortioxetine group appeared to switch to mania or hypomania.

Conclusions

This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage

while disease progression should be monitored closely for the risk of switching to mania.

关键词

双相抑郁鲁拉西酮沃替西汀联合治疗

Keywords

Bipolar II depressionLurasidoneVortioxetineCombination

references

Ali Z, Tegin C, El-Mallakh RS, 2020. Evaluating lurasidone as a treatment option for bipolar disorder. Expert Opin Pharmacother, 21(3):253-260. https://doi.org/10.1080/14656566.2019.1695777https://doi.org/10.1080/14656566.2019.1695777

Baldwin DS, Chrones L, Florea I, et al., 2016. The safety and tolerability of vortioxetine: analysis of data from randomized placebo-controlled trials and open-label extension studies. J Psychopharmacol, 30(3):242-252. https://doi.org/10.1177/0269881116628440https://doi.org/10.1177/0269881116628440

Bang-Andersen B, Ruhland T, Jørgensen M, et al., 2011. Discovery of 1-‍[2-‍(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem, 54(9):3206-3221. https://doi.org/10.1021/jm101459ghttps://doi.org/10.1021/jm101459g

Berhan A, Barker A, 2014. Vortioxetine in the treatment of adult patients with major depressive disorder: a meta-analysis of randomized double-blind controlled trials. BMC Psychiatry, 14:276. https://doi.org/10.1186/s12888-014-0276-xhttps://doi.org/10.1186/s12888-014-0276-x

Calabrese JR, Pikalov A, Streicher C, et al., 2017. Lurasidone in combination with lithium or valproate for the maintenance treatment of bipolar I disorder. Eur Neuropsychopharmacol, 27(9):865-876. https://doi.org/10.1016/j.euroneuro.2017.06.013https://doi.org/10.1016/j.euroneuro.2017.06.013

Calabrese JR, Durgam S, Satlin A, et al., 2021. Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial. Am J Psychiatry, 178(12):1098-1106. https://doi.org/10.1176/appi.ajp.2021.20091339https://doi.org/10.1176/appi.ajp.2021.20091339

Cheniaux E, Nardi AE, 2019. Evaluating the efficacy and safety of antidepressants in patients with bipolar disorder. Expert Opin Drug Saf, 18(10):893-913. https://doi.org/10.1080/14740338.2019.1651291https://doi.org/10.1080/14740338.2019.1651291

Cipriani A, Furukawa TA, Salanti G, et al., 2018. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet, 391(10128):1357-1366. https://doi.org/10.1016/S0140-6736(17)32802-7https://doi.org/10.1016/S0140-6736(17)32802-7

Clemente AS, Diniz BS, Nicolato R, et al., 2015. Bipolar disorder prevalence: a systematic review and meta-analysis of the literature. Braz J Psychiatry, 37(2):155-161. https://doi.org/10.1590/1516-4446-2012-1693https://doi.org/10.1590/1516-4446-2012-1693

Crump C, Sundquist K, Winkleby MA, et al., 2013. Comorbidities and mortality in bipolar disorder: a Swedish national cohort study. JAMA Psychiatry, 70(9):931-939. https://doi.org/10.1001/jamapsychiatry.2013.1394https://doi.org/10.1001/jamapsychiatry.2013.1394

D'Andrea G, de Ronchi D, Giaccotto L, et al., 2019. Vortioxetine treatment-emergent mania in the elderly: a case report. Australas Psychiatry, 27(4):413. https://doi.org/10.1177/1039856219839471https://doi.org/10.1177/1039856219839471

de Diego-Adelino J, Crespo JM, Mora F, et al., 2022. Vortioxetine in major depressive disorder: from mechanisms of action to clinical studies. An updated review. Expert Opin Drug Saf, 21(5):673-690. https://doi.org/10.1080/14740338.2022.2019705https://doi.org/10.1080/14740338.2022.2019705

DelBello MP, Goldman R, Phillips D, et al., 2017. Efficacy and safety of lurasidone in children and adolescents with bipolar I depression: a double-blind, placebo-controlled study. J Am Acad Child Adolesc Psychiatry, 56(12):1015-1025. https://doi.org/10.1016/j.jaac.2017.10.006https://doi.org/10.1016/j.jaac.2017.10.006

Dell'Osso B, Arici C, Cafaro R, et al., 2021. Antidepressants in bipolar disorder: analysis of correlates overall, and in BD-I and BD-II subsamples. J Affect Disord, 292:352-358. https://doi.org/10.1016/j.jad.2021.05.043https://doi.org/10.1016/j.jad.2021.05.043

Dome P, Rihmer Z, Gonda X, 2019. Suicide risk in bipolar disorder: a brief review. Medicina (Kaunas), 55(8):403. https://doi.org/10.3390/medicina55080403https://doi.org/10.3390/medicina55080403

Forte A, Baldessarini RJ, Tondo L, et al., 2015. Long-term morbidity in bipolar-I, bipolar-II, and unipolar major depressive disorders. J Affect Disord, 178:71-78. https://doi.org/10.1016/j.jad.2015.02.011https://doi.org/10.1016/j.jad.2015.02.011

Fountoulakis KN, Kelsoe JR, Akiskal H, 2012. Receptor targets for antidepressant therapy in bipolar disorder: an overview. J Affect Disord, 138(3):222-238. https://doi.org/10.1016/j.jad.2011.04.043https://doi.org/10.1016/j.jad.2011.04.043

Fountoulakis KN, Tohen M, Zarate CA, 2024. Pharmacodynamic properties of lumateperone and its efficacy in acute bipolar depression: a mechanistic hypothesis based on data. Eur Neuropsychopharmacol, 81:1-9. https://doi.org/10.1016/j.euroneuro.2024.01.002https://doi.org/10.1016/j.euroneuro.2024.01.002

Goldberg JF, Perlis RH, Bowden CL, et al., 2009. Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD. Am J Psychiatry, 166(2):173-181. https://doi.org/10.1176/appi.ajp.2008.08050746https://doi.org/10.1176/appi.ajp.2008.08050746

Grande I, Berk M, Birmaher B, et al., 2016. Bipolar disorder. Lancet, 387(10027):1561-1572. https://doi.org/10.1016/S0140-6736(15)00241-Xhttps://doi.org/10.1016/S0140-6736(15)00241-X

Greenberg WM, Citrome L, 2017. Pharmacokinetics and pharmacodynamics of lurasidone hydrochloride, a second-generation antipsychotic: a systematic review of the published literature. Clin Pharmacokinet, 56(5):493-503. https://doi.org/10.1007/s40262-016-0465-5https://doi.org/10.1007/s40262-016-0465-5

Ishibashi T, Horisawa T, Tokuda K, et al., 2010. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther, 334(1):171-181. https://doi.org/10.1124/jpet.110.167346https://doi.org/10.1124/jpet.110.167346

Kaltenboeck A, Winkler D, Kasper S, 2016. Bipolar and related disorders in DSM-5 and ICD-10. CNS Spectr, 21(4):318-323. https://doi.org/10.1017/S1092852916000079https://doi.org/10.1017/S1092852916000079

Kato T, Ishigooka J, Miyajima M, et al., 2020. Double-blind, placebo-controlled study of lurasidone monotherapy for the treatment of bipolar I depression. Psychiatry Clin Neurosci, 74(12):635-644. https://doi.org/10.1111/pcn.13137https://doi.org/10.1111/pcn.13137

Ketter TA, Sarma K, Silva R, et al., 2016. Lurasidone in the long-term treatment of patients with bipolar disorder: a 24-week open-label extension study. Depress Anxiety, 33(5):424-434. https://doi.org/10.1002/da.22479https://doi.org/10.1002/da.22479

Leverich GS, Altshuler LL, Frye MA, et al., 2006. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry, 163(2):232-239. https://doi.org/10.1176/appi.ajp.163.2.232https://doi.org/10.1176/appi.ajp.163.2.232

Li ZJ, Liu SH, Wu QX, et al., 2023. Effectiveness and safety of vortioxetine for the treatment of major depressive disorder in the real world: a systematic review and meta-analysis. Int J Neuropsychopharmacol, 26(6):373-384. https://doi.org/10.1093/ijnp/pyad018https://doi.org/10.1093/ijnp/pyad018

Liu BS, Zhang Y, Fang H, et al., 2017. Efficacy and safety of long-term antidepressant treatment for bipolar disorders—a meta-analysis of randomized controlled trials. J Affect Disord, 223:41-48. https://doi.org/10.1016/j.jad.2017.07.023https://doi.org/10.1016/j.jad.2017.07.023

Loebel A, Cucchiaro J, Silva R, et al., 2014a. Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry, 171(2):160-168. https://doi.org/10.1176/appi.ajp.2013.13070984https://doi.org/10.1176/appi.ajp.2013.13070984

Loebel A, Cucchiaro J, Silva R, et al., 2014b. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry, 171(2):169-177. https://doi.org/10.1176/appi.ajp.2013.13070985https://doi.org/10.1176/appi.ajp.2013.13070985

McGirr A, Vöhringer PA, Ghaemi SN, et al., 2016. Safety and efficacy of adjunctive second-generation antidepressant therapy with a mood stabiliser or an atypical antipsychotic in acute bipolar depression: a systematic review and meta-analysis of randomised placebo-controlled trials. Lancet Psychiatry, 3(12):1138-1146. https://doi.org/10.1016/S2215-0366(16)30264-4https://doi.org/10.1016/S2215-0366(16)30264-4

McIntyre RS, Calabrese JR, 2019. Bipolar depression: the clinical characteristics and unmet needs of a complex disorder. Curr Med Res Opin, 35(11):1993-2005. https://doi.org/10.1080/03007995.2019.1636017https://doi.org/10.1080/03007995.2019.1636017

McIntyre RS, Cha DS, Kim RD, et al., 2013. A review of FDA-approved treatment options in bipolar depression. CNS Spectr, 18(Suppl 1):4-20. https://doi.org/10.1017/S1092852913000746https://doi.org/10.1017/S1092852913000746

McIntyre RS, Suppes T, Earley W, et al., 2020. Cariprazine efficacy in bipolar I depression with and without concurrent manic symptoms: post hoc analysis of 3 randomized, placebo-controlled studies. CNS Spectr, 25(4):502-510. https://doi.org/10.1017/S1092852919001287https://doi.org/10.1017/S1092852919001287

Meltzer HY, Cucchiaro J, Silva R, et al., 2011. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry, 168(9):957-967. https://doi.org/10.1176/appi.ajp.2011.10060907https://doi.org/10.1176/appi.ajp.2011.10060907

Mitchell PB, Goodwin GM, Johnson GF, et al., 2008. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord, 10(1Pt 2):144-152. https://doi.org/10.1111/j.1399-5618.2007.00559.xhttps://doi.org/10.1111/j.1399-5618.2007.00559.x

Montgomery SA, Asberg M, 1979. A new depression scale designed to be sensitive to change. Br J Psychiatry, 134(4):382-389. https://doi.org/10.1192/bjp.134.4.382https://doi.org/10.1192/bjp.134.4.382

Mørk A, Pehrson A, Brennum LT, et al., 2012. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther, 340(3):666-675. https://doi.org/10.1124/jpet.111.189068https://doi.org/10.1124/jpet.111.189068

Pacchiarotti I, Verdolini N, 2021. Antidepressants in bipolar II depression: yes and no. Eur Neuropsychopharmacol, 47:48-50. https://doi.org/10.1016/j.euroneuro.2021.04.009https://doi.org/10.1016/j.euroneuro.2021.04.009

Pae CU, Wang SM, Han CS, et al., 2015. Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder. J Psychiatry Neurosci, 40(3):174-186. https://doi.org/10.1503/jpn.140120https://doi.org/10.1503/jpn.140120

Post RM, 2016. Treatment of bipolar depression: evolving recommendations. Psychiatr Clin North Am, 39(1):11-33. https://doi.org/10.1016/j.psc.2015.09.001https://doi.org/10.1016/j.psc.2015.09.001

Roberts RJ, Lohano KK, El-Mallakh RS, 2016. Antipsychotics as antidepressants. Asia Pac Psychiatry, 8(3):179-188. https://doi.org/10.1111/appy.12186https://doi.org/10.1111/appy.12186

Sheehan DV, Lecrubier Y, Sheehan KH, et al., 1998. The Mini-International Neuropsychiatric Interview (M.I.N.I): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry, 59(Suppl 20):22-33.

Sidor MM, Macqueen GM, 2011. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry, 72(2):156-167. https://doi.org/10.4088/JCP.09r05385grehttps://doi.org/10.4088/JCP.09r05385gre

Siwek M, Chrobak AA, Soltys Z, et al., 2022. A naturalistic, 24-week, open-label, add-on study of vortioxetine in bipolar depression. Psychiatr Pol, 56(3):509-522. https://doi.org/10.12740/PP/OnlineFirst/132962https://doi.org/10.12740/PP/OnlineFirst/132962

Sobreira G, Oliveira J, Brissos S, 2017. Vortioxetine-induced manic mood switch in patient with previously unknown bipolar disorder. Braz J Psychiatry, 39(1):86. https://doi.org/10.1590/1516-4446-2016-2113https://doi.org/10.1590/1516-4446-2016-2113

Suttajit S, Srisurapanont M, Maneeton N, et al., 2014. Quetiapine for acute bipolar depression: a systematic review and meta-analysis. Drug Des Devel Ther, 8:827-838. https://doi.org/10.2147/DDDT.S63779https://doi.org/10.2147/DDDT.S63779

Takaesu Y, Takeshima M, Watanabe K, 2022. Effectiveness and tolerability of lurasidone for bipolar types I and II and other specified bipolar depression: a 12-week observational study. J Clin Psychopharmacol, 42(5):485-488. https://doi.org/10.1097/JCP.0000000000001590https://doi.org/10.1097/JCP.0000000000001590

Terao T, 2021. Neglected but not negligible aspects of antidepressants and their availability in bipolar depression. Brain Behav, 11(8):e2308. https://doi.org/10.1002/brb3.2308https://doi.org/10.1002/brb3.2308

Tondo L, Baldessarini RJ, Vázquez G, et al., 2013. Clinical responses to antidepressants among 1036 acutely depressed patients with bipolar or unipolar major affective disorders. Acta Psychiatr Scand, 127(5):355-364. https://doi.org/10.1111/acps.12023https://doi.org/10.1111/acps.12023

Wong DF, Kuwabara H, Brašić JR, et al., 2013. Determination of dopamine D2 receptor occupancy by lurasidone using positron emission tomography in healthy male subjects. Psychopharmacology (Berl), 229(2):245-252. https://doi.org/10.1007/s00213-013-3103-zhttps://doi.org/10.1007/s00213-013-3103-z

Yalin N, Young AH, 2020. Pharmacological treatment of bipolar depression: what are the current and emerging options?Neuropsychiatr Dis Treat, 16:1459-1472. https://doi.org/10.2147/NDT.S245166https://doi.org/10.2147/NDT.S245166

Yatham LN, Kennedy SH, Parikh SV, et al., 2018. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord, 20(2):97-170. https://doi.org/10.1111/bdi.12609https://doi.org/10.1111/bdi.12609

Yoshikawa A, Li J, Meltzer HY, 2020. A functional HTR1A polymorphism, rs6295, predicts short-term response to lurasidone: confirmation with meta-analysis of other antipsychotic drugs. Pharmacogenomics J, 20(2):260-270. https://doi.org/10.1038/s41397-019-0101-5https://doi.org/10.1038/s41397-019-0101-5

Young RC, Biggs JT, Ziegler VE, et al., 1978. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry, 133:429-435. https://doi.org/10.1192/bjp.133.5.429https://doi.org/10.1192/bjp.133.5.429

浏览量

Downloads

CSCD

工具集

关联资源

暂无数据