Journal of Neurology

, Volume 267, Issue 1, pp 14–25 | Cite as

Acupuncture versus propranolol in migraine prophylaxis: an indirect treatment comparison meta-analysis

  • Yao-Yao Chen
  • Juan Li
  • Min Chen
  • Ling Yue
  • Tian-Wei She
  • Hui ZhengEmail author



Propranolol is recommended as first-line treatment for preventing migraine attacks; acupuncture has not been compared with propranolol in a head-to-head trial.


To compare acupuncture with propranolol using indirect treatment comparison meta-analysis.


We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Randomized controlled trials comparing acupuncture or propranolol with sham acupuncture, placebo, waiting-list control or usual care were included. We extracted information from the included trials using a standardized extraction form. The primary outcome was migraine episodes. The secondary outcomes included migraine days, migraine frequency, and adverse events.


We included 19 RCTs (n = 3656) after screening 1078 articles. The analysis showed that acupuncture had a significant advantage over propranolol in reducing migraine episodes over a 4-week period (SMD − 0.74, 95% CI − 1.04 to − 0.44). Acupuncture also had a significant advantage over waiting-list control in decreasing migraine frequency (SMD − 1.57, 95% CI − 2.08 to − 1.06). Acupuncture caused fewer adverse events than propranolol (RR 0.82, 95% CI 0.11–5.94).


Acupuncture had a better effect than propranolol in reducing migraine episodes in indirect comparison. The result should be confirmed in subsequent head-to-head studies.

Registration: PROSPERO CRD42018108585


Acupuncture Propranolol Migraine prophylaxis Indirect treatment comparison Meta-analysis 



The systematic review was financially supported by the National Natural Science Foundation of China (no. 81774321 and no. 81473777) granted to Min Chen and Hui Zheng, respectively, and it was also supported by Innovation Team Project from Chengdu University of Traditional Chinese Medicine (no. CXTD1701) granted to Hui Zheng.

Author contributions

HZ conceived the study design. MC developed the search strategy and searched the electronic databases. YY Chen and Min Chen screened the retrieved RCTs. JL and LY extracted information from the included RCTs, and TWS evaluated the risk of bias. HZ performed data synthesis. YYC and JL wrote the first draft of this manuscript, and all authors revised the manuscript and approved it for publication.

Compliance with ethical standards

Conflicts of interest

The authors have no conflict of interest to declare in this study.

Supplementary material

415_2019_9510_MOESM1_ESM.docx (15 kb)
Supplementary file1 (DOCX 15 kb)
415_2019_9510_MOESM2_ESM.docx (13 kb)
Supplementary file2 (DOCX 13 kb)


  1. 1.
    Manack AN, Buse DC, Lipton RB (2011) Chronic migraine: epidemiology and disease burden. Curr Pain Headache Rep 15:70–78. CrossRefPubMedGoogle Scholar
  2. 2.
    Buse DC, Lipton RB (2013) Global perspectives on the burden of episodic and chronic migraine. Cephalalgia 33:885–890. CrossRefPubMedGoogle Scholar
  3. 3.
    Vo P, Fang J, Bilitou A, Laflamme AK, Gupta S. Patients’ perspective on the burden of migraine in Europe: a cross-sectional analysis of survey data in France, Germany, Italy, Spain, and the United Kingdom. J Headache Pain 2018;19. doi:10.1186/s10194-018-0907-6.Google Scholar
  4. 4.
    Hawkins K, Wang S, Rupnow M (2010) Direct cost burden among insured US employees with migraine. Headache J Head Face Pain 48:553–563. CrossRefGoogle Scholar
  5. 5.
    Hazard E, Munakata J, Bigal ME, Rupnow MFT, Lipton RB (2009) The burden of migraine in the United States: current and emerging perspectives on disease management and economic analysis. Value Health 12:55–64. CrossRefPubMedGoogle Scholar
  6. 6.
    Carville S, Padhi S, Reason T, Underwood M, Guideline Development Group. Diagnosis and management of headaches in young people and adults: summary of NICE guidance. BMJ 2012;345:e5765. doi:10.1136/bmj.e5765.CrossRefGoogle Scholar
  7. 7.
    Rücker G, Schwarzer G (2015) Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med Res Methodol 15:58. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Nadelmann JW, Phil M, Stevens J, Saper JR (1986) Propranolol in the prophylaxis of migraine. Headache 26:175–182CrossRefGoogle Scholar
  9. 9.
    Ludin HP (1989) Flunarizine and propranolol in the treatment of migraine. Headache 29:219–224CrossRefGoogle Scholar
  10. 10.
    Gawel MJ, Kreeft J, Nelson RF, Simard D, Arnott WS (1992) Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine. Can J Neurol Sci 19:340–345CrossRefGoogle Scholar
  11. 11.
    Holroyd KA, Penzien DB, Cordingley GE (1991) Propranolol in the management of recurrent migraine: a meta-analytic review. Headache 31:333–340CrossRefGoogle Scholar
  12. 12.
    Kangasniemi P, Hedman C (1984) Metoprolol and propranolol in the prophylactic treatment of classical and common migraine. A double-blind study. Cephalalgia 4:91–96. CrossRefPubMedGoogle Scholar
  13. 13.
    Linde K, Allais G, Brinkhaus B, Fei Y, Mehring M, Vertosick EA, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev 2016:CD001218. doi:10.1002/14651858.CD001218.pub3.Google Scholar
  14. 14.
    Naderinabi B, Saberi A, Hashemi M, Haghighi M, Biazar G, Abolhasan Gharehdaghi F et al (2017) Acupuncture and botulinum toxin A injection in the treatment of chronic migraine: a randomized controlled study. Caspian J Intern Med 8:196–204. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wang L-P, Zhang X-Z, Guo J, Liu H-L, Zhang Y, Liu C-Z et al (2012) Efficacy of acupuncture for acute migraine attack: a multicenter single blinded, randomized controlled trial. Pain Med 13:623–630. CrossRefPubMedGoogle Scholar
  16. 16.
    Musil F, Pokladnikova J, Pavelek Z, Wang B, Guan X, Valis M (2018) Acupuncture in migraine prophylaxis in Czech patients: an open-label randomized controlled trial. Neuropsychiatr Dis Treat 14:1221–1228. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Xu J, Zhang FQ, Pei J, Ji J. Acupuncture for migraine without aura: a systematic review and meta-analysis. J Integr Med 2018.Google Scholar
  18. 18.
    Zhao L, Chen J, Li Y, Sun X, Chang X, Zheng H et al (2017) The long-term effect of acupuncture for migraine prophylaxis: a randomized clinical trial. JAMA Intern Med 177:508–515. CrossRefPubMedGoogle Scholar
  19. 19.
    Li Y, Zheng H, Witt CM, Roll S, Yu SG, Yan J et al (2012) Acupuncture for migraine prophylaxis: a randomized controlled trial. Can Med Assoc J. 184:401–410. CrossRefGoogle Scholar
  20. 20.
    Diener H-C, Kronfeld K, Boewing G, Lungenhausen M, Maier C, Molsberger A et al (2006) Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol 5:310–316. CrossRefPubMedGoogle Scholar
  21. 21.
    Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Foster NE et al (2012) Acupuncture for chronic pain: individual patient data meta-analysis. Arch Intern Med 172:1444–1453. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ (2011) The n-of-1 clinical trial: the ultimate strategy for individualizing medicine? Per Med 8:161–173. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Tfelt-Hansen P, Block G, Dahlöf C, Diener HC, Ferrari MD, Goadsby PJ, et al. Guidelines for controlled trials of drugs in migraine: second edition. Cephalalgia 2000;20:765–86. doi:10.1046/j.1468-2982.2000.00117.x.Google Scholar
  24. 24.
    Guyatt GH, Oxman AD, Sultan S, Glasziou P, Akl EA, Alonso-Coello P, et al. GRADE guidelines: 9. Rating up the quality of evidence. J Clin Epidemiol 2011;64:1311–6. doi:10.1016/j.jclinepi.2011.06.004.CrossRefGoogle Scholar
  25. 25.
    Rücker G (2012) Network meta-analysis, electrical networks and graph theory. Res Synth Methods 3:312–324. CrossRefPubMedGoogle Scholar
  26. 26.
    Mills EJ, Thorlund K, Ioannidis JPA (2013) Demystifying trial networks and network meta-analysis. BMJ 346:f2914. CrossRefPubMedGoogle Scholar
  27. 27.
    Riley RD, Jackson D, Salanti G, Burke DL, Price M, Kirkham J et al (2017) Multivariate and network meta-analysis of multiple outcomes and multiple treatments: rationale, concepts, and examples. BMJ 358:j3932. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Krahn U, Binder H, König J (2013) A graphical tool for locating inconsistency in network meta-analyses. BMC Med Res Methodol 13:35. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zhao L, Liu J, Zhang F, Dong X, Peng Y, Qin W et al (2014) Effects of long-term acupuncture treatment on resting-state brain activity in migraine patients: a randomized controlled trial on active acupoints and inactive acupoints. PLoS ONE 9:e99538. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Wang Y, Xue CC, Helme R, Da Costa C, Zheng Z (2015) Acupuncture for frequent migraine: a randomized, patient/assessor blinded, controlled trial with one-year follow-up. Evidence-Based Complement Alter Med 2015:1–14. CrossRefGoogle Scholar
  31. 31.
    Vickers AJ, Rees RW, Zollman CE, McCarney R, Smith CM, Ellis N et al (2004) Acupuncture for chronic headache in primary care: large, pragmatic, randomised trial. BMJ 328:744. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Streng A, Linde K, Hoppe A, Pfaffenrath V, Hammes M, Wagenpfeil S, et al. Effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis. Headache: The Journal of Head and Face Pain 2006;46:1492–502. doi:10.1111/j.1526–4610.2006.00598.x.Google Scholar
  33. 33.
    Salviz M, Yuce T, Acar H, Karatas A, Acikalin RM (2016) Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope 126:169–174. CrossRefPubMedGoogle Scholar
  34. 34.
    Melchart D, Thormaehlen J, Hager S, Liao J, Linde K, Weidenhammer W (2003) Acupuncture versus placebo versus sumatriptan for early treatment of migraine attacks: a randomized controlled trial. J Intern Med 253:181–188CrossRefGoogle Scholar
  35. 35.
    Lücking CH, Oestreich W, Schmidt R, Soyka D. Flunarizine vs. propranolol in the prophylaxis of migraine: two double-blind comparative studies in more than 400 patients. Cephalalgia 1988;8 Suppl 8:21–6. doi:10.1177/03331024880080S805.CrossRefGoogle Scholar
  36. 36.
    Linde M, Fjell A, Carlsson J, Dahlöf C (2005) Role of the Needling per se in Acupuncture as Prophylaxis for Menstrually Related Migraine: A Randomized Placebo-Controlled Study. Cephalalgia 25:41–47. CrossRefPubMedGoogle Scholar
  37. 37.
    Linde K, Streng A, Jürgens S, Hoppe A, Brinkhaus B, Witt C et al (2005) Acupuncture for patients with migraine: a randomized controlled trial. JAMA 293:2118–2125. CrossRefPubMedGoogle Scholar
  38. 38.
    Bordini CA, Arruda MA, Ciciarelli MC, Speciali JG (1997) Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. A double-blind trial Arq Neuropsiquiatr 55:536–541CrossRefGoogle Scholar
  39. 39.
    Ashtari F, Shaygannejad V, Akbari M (2008) A double-blind, randomized trial of low-dose topiramate vs propranolol in migraine prophylaxis. Acta Neurol Scand 118:301–305. CrossRefPubMedGoogle Scholar
  40. 40.
    Allais G, De Lorenzo C, Quirico PE, Airola G, Tolardo G, Mana O et al (2002) Acupuncture in the prophylactic treatment of migraine without aura: a comparison with flunarizine. Headache 42:855–861CrossRefGoogle Scholar
  41. 41.
    Alecrim-Andrade J, Maciel-Júnior JA, Carnè X, Severino Vasconcelos GM, Correa-Filho HR (2008) Acupuncture in migraine prevention: a randomized sham controlled study with 6-months posttreatment follow-up. Clin J Pain 24:98–105. CrossRefPubMedGoogle Scholar
  42. 42.
    Alecrim-Andrade J, Maciel-Júnior J, Cladellas X, Correa-Filho H, Machado H (2006) Acupuncture in Migraine Prophylaxis: A Randomized Sham-Controlled Trial. Cephalalgia 26:520–529. CrossRefPubMedGoogle Scholar
  43. 43.
    Ialongo C (2016) Understanding the effect size and its measures. Biochem Med (Zagreb) 26:150–163. CrossRefGoogle Scholar
  44. 44.
    Meissner K, Fässler M, Rücker G, Kleijnen J, Hróbjartsson A, Schneider A et al (2013) Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis. JAMA Intern Med 173:1941–1951CrossRefGoogle Scholar
  45. 45.
    Wang C, Liu B, Liu Y, He L, Li H, Liu J (2018) Analysis on the concepts related to adverse events and adverse reactions of acupuncture. Zhongguo Zhen Jiu 38:87–90. CrossRefPubMedGoogle Scholar
  46. 46.
    Lin J-G, Chen W-L (2008) Acupuncture analgesia: a review of its mechanisms of actions. Am J Chin Med 36:635–645. CrossRefPubMedGoogle Scholar
  47. 47.
    Zheng Y-Q, Wei W (2005) Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes. Int Immunopharmacol 5:1560–1573. CrossRefPubMedGoogle Scholar
  48. 48.
    Wickramasekera I (1980) A conditioned response model of the placebo effect predictions from the model. Biofeedback Self Regul 5:5–18CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Acupuncture and Tuina, The Third Teaching Hospital/Institute of Acupuncture and Homeostasis RegulationChengdu University of Traditional Chinese MedicineChengduChina
  2. 2.College of Health Preservation and RehabilitationChengdu University of Traditional Chinese MedicineChengduChina
  3. 3.Teaching Hospital/Clinical Medicine DepartmentChengdu University of Traditional Chinese MedicineChengduChina

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