Shexian Bupleurum Alleviates Insomnia and Improves Symptoms of Anxiety and Depression: A Randomized Double-Blind Placebo-Controlled Clinical Trial


Clinical trial
Randomized double-blind method
Shexian bupleurum




Objective: To observe the clinical efficacy of Shexian bupleurum on insomnia based on evaluation scales and polysomnogram (PSG). Methods: A total of 260 patients suffering from insomnia admitted to the outpatient department of Handan Central Hospital were included in a randomized, double blind, placebo-controlled trial. The patients were randomly divided into two groups: a control group (receiving placebo, n = 150), and an intervention group (receiving Shexian bupleurum treatment, n = 110). The clinical trial lasted for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ)-9, Generalized Anxiety Disorder (GAD)-7, 17 items of Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate the patients at baseline as well as two weeks and four weeks after treatment; the Treatment Emergent Symptom Scale (TESS) was used to evaluate adverse reactions; polysomnography (PSG) was used to monitor and analyze their sleep characteristics at baseline and four weeks after treatment. Results: The PSQI, ISI, PHQ-9, HAMD-17, and HAMA scores of the intervention group significantly decreased compared to the control group, while the total sleep time, rapid eye movement sleep latency, stage 2 sleep, deep sleep, rapid eye movement sleep, and sleep efficiency of the intervention group significantly increased compared to the control group. The PHQ-9 score of the control group only decreased two weeks after treatment (p < 0.05) compared to the intervention group. In addition, there were no obvious adverse events in both the intervention group and the control group. Conclusion: Shexian bupleurum not only improves sleep quality, but also relieves depression and anxiety in patients who suffer from insomnia.


Buysse DJ, 2013, Insomnia. JAMA, 309(7): 706–716.

Morin CM, Belanger L, LeBlanc M, et al., 2009, The Natural History of Insomnia: A Population-Based 3-Year Longitudinal Study. Arch Intern Med, 169(5): 447–453.

Shi Z, Lv J, 2015, Research Progress of Insomnia Status. Guangming J Chin Med, 30(6): 1376–1377.

Baglioni C, Battagliese G, Feige B, et al., 2011, Insomnia as a Predictor of Depression: A Meta-Analytic Evaluation of Longitudinal Epidemiological Studies. J Affect Disord, 135(1–3): 10–19.

Zambotti M, Goldstone A, Colrain IM, et al., 2018, Insomnia Disorder in Adolescence: Diagnosis, Impact, and Treatment. Sleep Med Rev, 39: 12–24.

Ribeiro JD, Pease JL, Gutierrez PM, et al., 2012, Sleep Problems Outperform Depression and Hopelessness as Cross-Sectional and Longitudinal Predictors of Suicidal Ideation and Behavior in Young Adults in the Military. J Affect Disord, 136(3): 743–750.

McCall WV, 2001, A Psychiatric Perspective on Insomnia. J Clin Psychiatry, 62(Suppl 10): 27–32.

Mason EC, Harvey AG, 2014, Insomnia Before and After Treatment for Anxiety and Depression. J Affect Disord, 168: 415–421.

Gebara MA, Siripong N, DiNapoli EA, et al., 2018, Effect of Insomnia Treatments on Depression: A Systematic Review and Meta-Analysis. Depress Anxiety, 35(8): 717–731.

Vgontzas AN, Liao D, Pejovic S, et al., 2009, Insomnia with Objective Short Sleep Duration Is Associated with Type 2 Diabetes: A Population-Based Study. Diabetes Care, 32(11): 1980–1985.

Fernandez-Mendoza J, Vgontzas AN, Liao D, et al., 2012, Insomnia with Objective Short Sleep Duration and Incident Hypertension: The Penn State Cohort. Hypertension, 60(4): 929–935.

Laugsand LE, Strand LB, Platou C, et al., 2014, Insomnia and the Risk of Incident Heart Failure: A Population Study. Eur Heart J, 35(21): 1382–1393.

Sands-Lincoln M, Loucks EB, Lu B, et al., 2013, Sleep Duration, Insomnia, and Coronary Heart Disease Among Postmenopausal Women in the Women’s Health Initiative. J Womens Health, 22(6): 477–486.

Laugsand LE, Vatten LJ, Platou C, et al., 2011, Insomnia and the Risk of Acute Myocardial Infarction: A Population Study. Circulation, 124(19): 2073–2081.

National Institutes of Health, 2005, National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults, June 13–15, 2005. Sleep, 28(9): 1049–1057.

Tannenbaum C, Diaby V, Singh D, et al., 2015, Sedative-Hypnotic Medicines and Falls in Community-Dwelling Older Adults: A Cost-Effectiveness (Decision-Tree) Analysis from a US Medicare Perspective. Drugs Aging, 32(4): 305–314.

Pchelina PV, Poluektov MG, 2019, Cognitive-Behavioral Therapy and Pharmacotherapy for Chronic Insomnia. Zh Nevrol Psikhiatr Im S S Korsakova, 119(4. Vyp. 2): 22–27.

Hassinger AB, Bletnisky N, Dudekula R, et al., 2020, Selecting a Pharmacotherapy Regimen for Patients with Chronic Insomnia. Expert Opin Pharmacother, 21(9): 1035–1043.

Mitchell MD, Gehrman P, Perlis M, et al., 2012, Comparative Effectiveness of Cognitive Behavioral Therapy for Insomnia: A Systematic Review. BMC Fam Pract, 13(1): 40.

Ni X, Shergis JL, Guo X, et al., 2015, Updated Clinical Evidence of Chinese Herbal Medicine for Insomnia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sleep Med, 16(12): 1462–1481.

Singh A, Zhao K, 2017, Treatment of Insomnia with Traditional Chinese Herbal Medicine. Int Rev Neurobiol, 135: 97–115.

Wang C, Yang Y, Ding X, et al., 2021, Efficacy and Safety of Shumian Capsules in Treating Insomnia: A Systematic Review and Meta-Analysis. Medicine, 100(50): e28194.

Kushida CA, Littner MR, Morgenthaler T, et al., 2005, Practice Parameters for the Indications for Polysomnography and Related Procedures: An Update for 2005. Sleep, 28(4): 499–521.

Littner M, Hirshkowitz M, Kramer M, et al., 2003, Practice Parameters for Using Polysomnography to Evaluate Insomnia: An Update. Sleep, 26(6): 754–760.

Buysse DJ, Reynolds CF, Monk TH, et al., 1989, The Pittsburgh Sleep Quality Index: A New Instrument for Psychiatric Practice and Research. Psychiatry Res, 28(2): 193–213.

Morin CM, Belleville G, Belanger L, et al., 2011, The Insomnia Severity Index: Psychometric Indicators to Detect Insomnia Cases and Evaluate Treatment Response. Sleep, 34(5): 601–608.

Spitzer RL, Kroenke K, Williams JB, et al., 2006, A Brief Measure for Assessing Generalized Anxiety Disorder: The GAD-7. Arch Intern Med, 166(10): 1092–1097.

Richard BB, Claude LA, Susan MH, et al., 2018, The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Version 2.5. IL, American Academy of Sleep Medicine, Darien.

Xie M, Liao M, 2001, Shumian Capsule. Chin J New Drugs, 10(5): 386.

Liang F, Zhang X, Jiang X, et al., 2021, Experimental Study on the Effects of Shumian Capsule on Sedation and Hypnosis and Its Mechanisms. J Xi’an Jiaotong Univ, 42(1): 168–174.

Neurology CSo, Sleep Disorder Society CSoN, 2018, Guideline for the Evaluation and Treatment of Insomnia in Chinese Adults (2017). Chin J Neurol, 51(5): 324–335.

Li C, Li D, Zheng H, et al., 2007, Influence of Estazolam on the Sleep Quality and Daytime Function of Patients with Insomnia. J Clin Rehabil Tissue Eng Res, 11(52): 10483–10485.

An X, Duan L, Zhang YH, et al., 2021, The Three Syndromes and Six Chinese Patent Medicine Study During the Recovery Phase of COVID-19. Chin Med, 16(1): 44.